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  • Review Article
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Sexual dimorphism in cardiometabolic health: the role of adipose tissue, muscle and liver

Nature Reviews Endocrinology volume 17, pages 47–66 (2021)Cite this article

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Abstract

Obesity is associated with many adverse health effects, such as an increased cardiometabolic risk. Despite higher adiposity for a given BMI, premenopausal women are at lower risk of cardiometabolic disease than men of the same age. This cardiometabolic advantage in women seems to disappear after the menopause or when type 2 diabetes mellitus develops. Sexual dimorphism in substrate supply and utilization, deposition of excess lipids and mobilization of stored lipids in various key metabolic organs (such as adipose tissue, skeletal muscle and the liver) are associated with differences in tissue-specific insulin sensitivity and cardiometabolic risk profiles between men and women. Moreover, lifestyle-related factors and epigenetic and genetic mechanisms seem to affect metabolic complications and disease risk in a sex-specific manner. This Review provides insight into sexual dimorphism in adipose tissue distribution, adipose tissue, skeletal muscle and liver substrate metabolism and tissue-specific insulin sensitivity in humans, as well as the underlying mechanisms, and addresses the effect of these sex differences on cardiometabolic health. Additionally, this Review highlights the implications of sexual dimorphism in the pathophysiology of obesity-related cardiometabolic risk for the development of sex-specific prevention and treatment strategies.

Key points

  • Premenopausal women have a lower risk of cardiometabolic diseases than men of the same age and BMI; however, this effect disappears with deterioration of glucose homeostasis and after the menopause.

  • Premenopausal women have a higher adipose tissue mass for a given BMI but store a higher proportion of excess energy in subcutaneous adipose tissue, predominantly in lower body adipose depots, than men.

  • Sexual dimorphism in adipose distribution and adipose tissue, skeletal muscle and liver substrate metabolism contributes considerably to sex differences in tissue-specific insulin sensitivity and cardiometabolic health.

  • Further deciphering sex-specific regulation of human metabolism in key metabolic organs is needed to optimize age-specific and sex-specific strategies to prevent and treat obesity-related cardiometabolic complications.

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Fig. 1: Key aspects of sexual dimorphism in body composition, adipose tissue distribution and metabolic homeostasis in humans.
Fig. 2: Menopause induces insulin resistance and increases cardiometabolic disease risk in women.
Fig. 3: Sexual dimorphism in the metabolic and endocrine function of adipose tissue in humans.
Fig. 4: Sexual dimorphism in skeletal muscle metabolism in humans.
Fig. 5: Sexual dimorphism in liver metabolism in humans.

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References

  1. Kopelman, P. G. Obesity as a medical problem. Nature 404, 635–643 (2000).

    CAS  PubMed  Google Scholar 

  2. Sheridan, S., Pignone, M. & Mulrow, C. Framingham-based tools to calculate the global risk of coronary heart disease: a systematic review of tools for clinicians. J. Gen. Intern. Med. 18, 1039–1052 (2003).

    PubMed  PubMed Central  Google Scholar 

  3. Beery, A. K. & Zucker, I. Sex bias in neuroscience and biomedical research. Neurosci. Biobehav. Rev. 35, 565–572 (2011).

    PubMed  Google Scholar 

  4. Hu, G., Jousilahti, P., Qiao, Q., Katoh, S. & Tuomilehto, J. Sex differences in cardiovascular and total mortality among diabetic and non-diabetic individuals with or without history of myocardial infarction. Diabetologia 48, 856–861 (2005).

    CAS  PubMed  Google Scholar 

  5. Kannel, W. B. & Wilson, P. W. Risk factors that attenuate the female coronary disease advantage. Arch. Intern. Med. 155, 57–61 (1995).

    CAS  PubMed  Google Scholar 

  6. Regensteiner, J. G. et al. Sex differences in the cardiovascular consequences of diabetes mellitus: a scientific statement from the American Heart Association. Circulation 132, 2424–2447 (2015).

    PubMed  Google Scholar 

  7. Wild, S., Roglic, G., Green, A., Sicree, R. & King, H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27, 1047–1053 (2004).

    Google Scholar 

  8. Peters, S. A. E., Muntner, P. & Woodward, M. Sex differences in the prevalence of, and trends in, cardiovascular risk factors, treatment, and control in the United States, 2001 to 2016. Circulation 139, 1025–1035 (2019).

    CAS  PubMed  Google Scholar 

  9. Cho, N. H. et al. IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res. Clin. Pract. 138, 271–281 (2018).

    CAS  PubMed  Google Scholar 

  10. Kuhl, J. et al. Characterisation of subjects with early abnormalities of glucose tolerance in the Stockholm Diabetes Prevention Programme: the impact of sex and type 2 diabetes heredity. Diabetologia 48, 35–40 (2005).

    CAS  PubMed  Google Scholar 

  11. Munguia-Miranda, C., Sanchez-Barrera, R. G., Tuz, K., Alonso-Garcia, A. L. & Cruz, M. Impaired fasting glucose detection in blood donors population. Rev. Med. Inst. Mex. Seguro Soc. 47, 17–24 (2009).

    PubMed  Google Scholar 

  12. The Decode Study Group. Age- and sex-specific prevalences of diabetes and impaired glucose regulation in 13 European cohorts. Diabetes Care 26, 61–69 (2003).

    Google Scholar 

  13. Glumer, C., Jorgensen, T. & Borch-Johnsen, K. Prevalences of diabetes and impaired glucose regulation in a Danish population: the Inter99 study. Diabetes Care 26, 2335–2340 (2003).

    PubMed  Google Scholar 

  14. Clausen, J. O. et al. Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors. J. Clin. Invest. 98, 1195–1209 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Faerch, K., Borch-Johnsen, K., Vaag, A., Jorgensen, T. & Witte, D. R. Sex differences in glucose levels: a consequence of physiology or methodological convenience? The Inter99 study. Diabetologia 53, 858–865 (2010).

    CAS  PubMed  Google Scholar 

  16. Anderwald, C. et al. Mechanism and effects of glucose absorption during an oral glucose tolerance test among females and males. J. Clin. Endocrinol. Metab. 96, 515–524 (2011).

    CAS  PubMed  Google Scholar 

  17. Karakelides, H., Irving, B. A., Short, K. R., O’Brien, P. & Nair, K. S. Age, obesity, and sex effects on insulin sensitivity and skeletal muscle mitochondrial function. Diabetes 59, 89–97 (2010).

    CAS  PubMed  Google Scholar 

  18. Hoeg, L. et al. Higher intramuscular triacylglycerol in women does not impair insulin sensitivity and proximal insulin signaling. J. Appl. Physiol. 107, 824–831 (2009).

    PubMed  Google Scholar 

  19. Vistisen, B. et al. Effect of gender on lipid-induced insulin resistance in obese subjects. Eur. J. Endocrinol. 158, 61–68 (2008).

    CAS  PubMed  Google Scholar 

  20. Borissova, A. M., Tankova, T., Kirilov, G. & Koev, D. Gender-dependent effect of ageing on peripheral insulin action. Int. J. Clin. Pract. 59, 422–426 (2005).

    PubMed  Google Scholar 

  21. Sumner, A. E. et al. Sex differences in African-Americans regarding sensitivity to insulin’s glucoregulatory and antilipolytic actions. Diabetes Care 22, 71–77 (1999).

    CAS  PubMed  Google Scholar 

  22. Nuutila, P. et al. Gender and insulin sensitivity in the heart and in skeletal muscles. Studies using positron emission tomography. Diabetes 44, 31–36 (1995).

    CAS  PubMed  Google Scholar 

  23. Hoeg, L. D. et al. Lipid-induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling. Diabetes 60, 64–73 (2011).

    PubMed  Google Scholar 

  24. Koska, J. et al. Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals. Am. J. Clin. Nutr. 87, 295–302 (2008).

    CAS  PubMed  Google Scholar 

  25. Soeters, M. R. et al. Gender-related differences in the metabolic response to fasting. J. Clin. Endocrinol. Metab. 92, 3646–3652 (2007).

    CAS  PubMed  Google Scholar 

  26. Shadid, S., Kanaley, J. A., Sheehan, M. T. & Jensen, M. D. Basal and insulin-regulated free fatty acid and glucose metabolism in humans. Am. J. Physiol. Endocrinol. Metab. 292, E1770–E1774 (2007).

    CAS  PubMed  Google Scholar 

  27. Rattarasarn, C., Leelawattana, R., Soonthornpun, S., Setasuban, W. & Thamprasit, A. Gender differences of regional abdominal fat distribution and their relationships with insulin sensitivity in healthy and glucose-intolerant Thais. J. Clin. Endocrinol. Metab. 89, 6266–6270 (2004).

    CAS  PubMed  Google Scholar 

  28. Frias, J. P. et al. Decreased susceptibility to fatty acid-induced peripheral tissue insulin resistance in women. Diabetes 50, 1344–1350 (2001).

    CAS  PubMed  Google Scholar 

  29. Donahue, R. P., Prineas, R. J., DeCarlo Donahue, R., Bean, J. A. & Skyler, J. S. The female ‘insulin advantage’ in a biracial cohort: results from the Miami Community Health Study. Int. J. Obes. Relat. Metab. Disord. 20, 76–82 (1996).

    CAS  PubMed  Google Scholar 

  30. Yki-Jarvinen, H. Sex and insulin sensitivity. Metabolism 33, 1011–1015 (1984).

    CAS  PubMed  Google Scholar 

  31. Gannon, M., Kulkarni, R. N., Tse, H. M. & Mauvais-Jarvis, F. Sex differences underlying pancreatic islet biology and its dysfunction. Mol. Metab. 15, 82–91 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Tramunt, B. et al. Sex differences in metabolic regulation and diabetes susceptibility. Diabetologia 63, 453–461 (2020).

    PubMed  Google Scholar 

  33. Polotsky, H. N. & Polotsky, A. J. Metabolic implications of menopause. Semin. Reprod. Med. 28, 426–434 (2010).

    PubMed  Google Scholar 

  34. Perseghin, G. et al. Gender factors affect fatty acids-induced insulin resistance in nonobese humans: effects of oral steroidal contraception. J. Clin. Endocrinol. Metab. 86, 3188–3196 (2001).

    CAS  PubMed  Google Scholar 

  35. Polderman, K. H., Gooren, L. J., Asscheman, H., Bakker, A. & Heine, R. J. Induction of insulin resistance by androgens and estrogens. J. Clin. Endocrinol. Metab. 79, 265–271 (1994).

    CAS  PubMed  Google Scholar 

  36. Margolis, K. L. et al. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women’s Health Initiative Hormone Trial. Diabetologia 47, 1175–1187 (2004).

    CAS  Google Scholar 

  37. Bruns, C. M. & Kemnitz, J. W. Sex hormones, insulin sensitivity, and diabetes mellitus. ILAR J. 45, 160–169 (2004).

    CAS  PubMed  Google Scholar 

  38. Smith, E. P. et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N. Engl. J. Med. 331, 1056–1061 (1994).

    CAS  PubMed  Google Scholar 

  39. Palmisano, B. T., Zhu, L., Eckel, R. H. & Stafford, J. M. Sex differences in lipid and lipoprotein metabolism. Mol. Metab. 15, 45–55 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Cox-York, K. A. et al. The effects of sex, metabolic syndrome and exercise on postprandial lipemia. Metabolism 62, 244–254 (2013).

    CAS  PubMed  Google Scholar 

  41. Magkos, F., Patterson, B. W., Mohammed, B. S., Klein, S. & Mittendorfer, B. Women produce fewer but triglyceride-richer very low-density lipoproteins than men. J. Clin. Endocrinol. Metab. 92, 1311–1318 (2007).

    CAS  PubMed  Google Scholar 

  42. Magkos, F., Mohammed, B. S. & Mittendorfer, B. Plasma lipid transfer enzymes in non-diabetic lean and obese men and women. Lipids 44, 459–464 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Cohn, J. S., McNamara, J. R., Cohn, S. D., Ordovas, J. M. & Schaefer, E. J. Postprandial plasma lipoprotein changes in human subjects of different ages. J. Lipid Res. 29, 469–479 (1988).

    CAS  PubMed  Google Scholar 

  44. Couillard, C. et al. Gender difference in postprandial lipemia: importance of visceral adipose tissue accumulation. Arterioscler. Thromb. Vasc. Biol. 19, 2448–2455 (1999).

    CAS  PubMed  Google Scholar 

  45. Horton, T. J., Commerford, S. R., Pagliassotti, M. J. & Bessesen, D. H. Postprandial leg uptake of triglyceride is greater in women than in men. Am. J. Physiol. Endocrinol. Metab. 283, E1192–E1202 (2002).

    CAS  PubMed  Google Scholar 

  46. Karastergiou, K. et al. Distinct developmental signatures of human abdominal and gluteal subcutaneous adipose tissue depots. J. Clin. Endocrinol. Metab. 98, 362–371 (2013).

    CAS  PubMed  Google Scholar 

  47. Wang, X., Magkos, F. & Mittendorfer, B. Sex differences in lipid and lipoprotein metabolism: it’s not just about sex hormones. J. Clin. Endocrinol. Metab. 96, 885–893 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Matthews, K. A. et al. Menopause and risk factors for coronary heart disease. N. Engl. J. Med. 321, 641–646 (1989).

    CAS  PubMed  Google Scholar 

  49. Masding, M. G., Stears, A. J., Burdge, G. C., Wootton, S. A. & Sandeman, D. D. Premenopausal advantages in postprandial lipid metabolism are lost in women with type 2 diabetes. Diabetes Care 26, 3243–3249 (2003).

    PubMed  Google Scholar 

  50. Goossens, G. H. The metabolic phenotype in obesity: fat mass, body fat distribution, and adipose tissue function. Obes. Facts 10, 207–215 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. van Meijel R. L. J., Blaak E. E. & Goossens G. H. In Mechanisms and Manifestations of Obesity in Lung Disease. (eds Johnston R. A. & Suratt B. T.) 1–22 (Elsevier, 2019).

  52. Yuan, Y., Gao, J. & Ogawa, R. Mechanobiology and mechanotherapy of adipose tissue–effect of mechanical force on fat tissue engineering. Plast. Reconstr. Surg. Glob. Open 3, e578 (2015).

    PubMed  Google Scholar 

  53. Bohler, H. Jr., Mokshagundam, S. & Winters, S. J. Adipose tissue and reproduction in women. Fertil. Steril. 94, 795–825 (2010).

    CAS  PubMed  Google Scholar 

  54. Lafontan, M. & Langin, D. Lipolysis and lipid mobilization in human adipose tissue. Prog. Lipid Res. 48, 275–297 (2009).

    CAS  PubMed  Google Scholar 

  55. Fruhbeck, G. Overview of adipose tissue and its role in obesity and metabolic disorders. Methods Mol. Biol. 456, 1–22 (2008).

    PubMed  Google Scholar 

  56. Nielsen, S., Guo, Z., Johnson, C. M., Hensrud, D. D. & Jensen, M. D. Splanchnic lipolysis in human obesity. J. Clin. Invest. 113, 1582–1588 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Rebuffe-Scrive, M. et al. Fat cell metabolism in different regions in women. Effect of menstrual cycle, pregnancy, and lactation. J. Clin. Invest. 75, 1973–1976 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Bowman, K. et al. Central adiposity and the overweight risk paradox in aging: follow-up of 130,473 UK Biobank participants. Am. J. Clin. Nutr. 106, 130–135 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Karpe, F. & Pinnick, K. E. Biology of upper-body and lower-body adipose tissue–link to whole-body phenotypes. Nat. Rev. Endocrinol. 11, 90–100 (2015).

    CAS  PubMed  Google Scholar 

  60. Camhi, S. M. et al. The relationship of waist circumference and BMI to visceral, subcutaneous, and total body fat: sex and race differences. Obesity 19, 402–408 (2011).

    PubMed  Google Scholar 

  61. Goodpaster, B. H. et al. Obesity, regional body fat distribution, and the metabolic syndrome in older men and women. Arch. Intern. Med. 165, 777–783 (2005).

    PubMed  Google Scholar 

  62. Kvist, H., Chowdhury, B., Grangard, U., Tylen, U. & Sjostrom, L. Total and visceral adipose-tissue volumes derived from measurements with computed tomography in adult men and women: predictive equations. Am. J. Clin. Nutr. 48, 1351–1361 (1988).

    CAS  PubMed  Google Scholar 

  63. Lemieux, S., Prud’homme, D., Bouchard, C., Tremblay, A. & Despres, J. P. Sex differences in the relation of visceral adipose tissue accumulation to total body fatness. Am. J. Clin. Nutr. 58, 463–467 (1993).

    CAS  PubMed  Google Scholar 

  64. Pi-Sunyer, F. X. The epidemiology of central fat distribution in relation to disease. Nutr. Rev. 62, S120–S126 (2004).

    PubMed  Google Scholar 

  65. Tchkonia, T. et al. Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots. Am. J. Physiol. Endocrinol. Metab. 288, E267–E277 (2005).

    CAS  PubMed  Google Scholar 

  66. Drolet, R. et al. Hypertrophy and hyperplasia of abdominal adipose tissues in women. Int. J. Obes. 32, 283–291 (2008).

    CAS  Google Scholar 

  67. Andersson, D. P., Arner, E., Hogling, D. E., Ryden, M. & Arner, P. Abdominal subcutaneous adipose tissue cellularity in men and women. Int. J. Obes. 41, 1564–1569 (2017).

    CAS  Google Scholar 

  68. Tchoukalova, Y. D. et al. Sex- and depot-dependent differences in adipogenesis in normal-weight humans. Obesity 18, 1875–1880 (2010).

    PubMed  Google Scholar 

  69. Gustafson, B., Nerstedt, A. & Smith, U. Reduced subcutaneous adipogenesis in human hypertrophic obesity is linked to senescent precursor cells. Nat. Commun. 10, 2757 (2019).

    PubMed  PubMed Central  Google Scholar 

  70. Tchoukalova, Y. D. et al. Subcutaneous adipocyte size and body fat distribution. Am. J. Clin. Nutr. 87, 56–63 (2008).

    CAS  PubMed  Google Scholar 

  71. Gao, H. et al. CD36 is a marker of human adipocyte progenitors with pronounced adipogenic and triglyceride accumulation potential. Stem Cell 35, 1799–1814 (2017).

    CAS  Google Scholar 

  72. Lessard, J. et al. Low abdominal subcutaneous preadipocyte adipogenesis is associated with visceral obesity, visceral adipocyte hypertrophy, and a dysmetabolic state. Adipocyte 3, 197–205 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. White, U. A., Fitch, M. D., Beyl, R. A., Hellerstein, M. K. & Ravussin, E. Differences in in vivo cellular kinetics in abdominal and femoral subcutaneous adipose tissue in women. Diabetes 65, 1642–1647 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Tchoukalova, Y. D. et al. Regional differences in cellular mechanisms of adipose tissue gain with overfeeding. Proc. Natl Acad. Sci. USA 107, 18226–18231 (2010).

    CAS  PubMed  Google Scholar 

  75. Pope, B. D., Warren, C. R., Parker, K. K. & Cowan, C. A. Microenvironmental control of adipocyte fate and function. Trends Cell Biol. 26, 745–755 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Sun, K., Kusminski, C. M. & Scherer, P. E. Adipose tissue remodeling and obesity. J. Clin. Invest. 121, 2094–2101 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Baker, N. A. et al. Diabetes-specific regulation of adipocyte metabolism by the adipose tissue extracellular matrix. J. Clin. Endocrinol. Metab. 102, 1032–1043 (2017).

    PubMed  PubMed Central  Google Scholar 

  78. Svendsen, O. L., Hassager, C. & Christiansen, C. Age- and menopause-associated variations in body composition and fat distribution in healthy women as measured by dual-energy X-ray absorptiometry. Metabolism 44, 369–373 (1995).

    CAS  PubMed  Google Scholar 

  79. Ley, C. J., Lees, B. & Stevenson, J. C. Sex- and menopause-associated changes in body-fat distribution. Am. J. Clin. Nutr. 55, 950–954 (1992).

    CAS  PubMed  Google Scholar 

  80. Lovejoy, J. C., Champagne, C. M., de Jonge, L., Xie, H. & Smith, S. R. Increased visceral fat and decreased energy expenditure during the menopausal transition. Int. J. Obes. 32, 949–958 (2008).

    CAS  Google Scholar 

  81. Toth, M. J., Tchernof, A., Sites, C. K. & Poehlman, E. T. Effect of menopausal status on body composition and abdominal fat distribution. Int. J. Obes. Relat. Metab. Disord. 24, 226–231 (2000).

    CAS  PubMed  Google Scholar 

  82. Carmina, E. et al. Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J. Clin. Endocrinol. Metab. 92, 2500–2505 (2007).

    CAS  PubMed  Google Scholar 

  83. Puder, J. J. et al. Central fat excess in polycystic ovary syndrome: relation to low-grade inflammation and insulin resistance. J. Clin. Endocrinol. Metab. 90, 6014–6021 (2005).

    CAS  PubMed  Google Scholar 

  84. Elbers, J. M., Asscheman, H., Seidell, J. C. & Gooren, L. J. Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals. Am. J. Physiol. 276, E317–E325 (1999).

    CAS  PubMed  Google Scholar 

  85. Lapid, K., Lim, A., Clegg, D. J., Zeve, D. & Graff, J. M. Oestrogen signalling in white adipose progenitor cells inhibits differentiation into brown adipose and smooth muscle cells. Nat. Commun. 5, 5196 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Dieudonne, M. N., Pecquery, R., Leneveu, M. C. & Giudicelli, Y. Opposite effects of androgens and estrogens on adipogenesis in rat preadipocytes: evidence for sex and site-related specificities and possible involvement of insulin-like growth factor 1 receptor and peroxisome proliferator-activated receptor gamma2. Endocrinology 141, 649–656 (2000).

    CAS  PubMed  Google Scholar 

  87. Anderson, L. A., McTernan, P. G., Barnett, A. H. & Kumar, S. The effects of androgens and estrogens on preadipocyte proliferation in human adipose tissue: influence of gender and site. J. Clin. Endocrinol. Metab. 86, 5045–5051 (2001).

    CAS  PubMed  Google Scholar 

  88. Cox-York, K. A., Erickson, C. B., Pereira, R. I., Bessesen, D. H. & Van Pelt, R. E. Region-specific effects of oestradiol on adipose-derived stem cell differentiation in post-menopausal women. J. Cell Mol. Med. 21, 677–684 (2017).

    CAS  PubMed  Google Scholar 

  89. Salpeter, S. R. et al. Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes. Metab. 8, 538–554 (2006).

    CAS  PubMed  Google Scholar 

  90. Ihunnah, C. A. et al. Estrogen sulfotransferase/SULT1E1 promotes human adipogenesis. Mol. Cell Biol. 34, 1682–1694 (2014).

    PubMed  PubMed Central  Google Scholar 

  91. Mauvais-Jarvis, F., Clegg, D. J. & Hevener, A. L. The role of estrogens in control of energy balance and glucose homeostasis. Endocr. Rev. 34, 309–338 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Garaulet, M. et al. Body fat distribution in pre-and post-menopausal women: metabolic and anthropometric variables. J. Nutr. Health Aging 6, 123–126 (2002).

    CAS  PubMed  Google Scholar 

  93. Taylor, R. W., Grant, A. M., Williams, S. M. & Goulding, A. Sex differences in regional body fat distribution from pre- to postpuberty. Obesity 18, 1410–1416 (2010).

    PubMed  Google Scholar 

  94. Tran, T. T. & Kahn, C. R. Transplantation of adipose tissue and stem cells: role in metabolism and disease. Nat. Rev. Endocrinol. 6, 195–213 (2010).

    PubMed  PubMed Central  Google Scholar 

  95. Heid, I. M. et al. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat. Genet. 42, 949–960 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Lindgren, C. M. et al. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genet. 5, e1000508 (2009).

    PubMed  PubMed Central  Google Scholar 

  97. Pinnick, K. E. et al. Distinct developmental profile of lower-body adipose tissue defines resistance against obesity-associated metabolic complications. Diabetes 63, 3785–3797 (2014).

    CAS  PubMed  Google Scholar 

  98. Grove, K. L., Fried, S. K., Greenberg, A. S., Xiao, X. Q. & Clegg, D. J. A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice. Int. J. Obes. 34, 989–1000 (2010).

    CAS  Google Scholar 

  99. van Nas, A. et al. Elucidating the role of gonadal hormones in sexually dimorphic gene coexpression networks. Endocrinology 150, 1235–1249 (2009).

    PubMed  Google Scholar 

  100. Gesta, S. et al. Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proc. Natl Acad. Sci. USA 103, 6676–6681 (2006).

    CAS  PubMed  Google Scholar 

  101. Zore, T., Palafox, M. & Reue, K. Sex differences in obesity, lipid metabolism, and inflammation–a role for the sex chromosomes? Mol. Metab. 15, 35–44 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Lempesis I. G., van Meijel R. L. J., Manolopoulos K. N. & Goossens G. H. Oxygenation of adipose tissue: a human perspective. Acta Physiol. 2019, e13298.

  103. Stinkens, R., Goossens, G. H., Jocken, J. W. & Blaak, E. E. Targeting fatty acid metabolism to improve glucose metabolism. Obes. Rev. 16, 715–757 (2015).

    CAS  PubMed  Google Scholar 

  104. Goossens, G. H. The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol. Behav. 94, 206–218 (2008).

    CAS  PubMed  Google Scholar 

  105. Rosen, E. D. & Spiegelman, B. M. What we talk about when we talk about fat. Cell 156, 20–44 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Fuster, J. J., Ouchi, N., Gokce, N. & Walsh, K. Obesity-induced changes in adipose tissue microenvironment and their impact on cardiovascular disease. Circ. Res. 118, 1786–1807 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Goossens, G. H. & Blaak, E. E. Adipose tissue dysfunction and impaired metabolic health in human obesity: a matter of oxygen? Front. Endocrinol. 6, 55 (2015).

    Google Scholar 

  108. Fonseca, V. Effect of thiazolidinediones on body weight in patients with diabetes mellitus. Am. J. Med. 115 (Suppl. 8A), 42S–48S (2003).

    CAS  PubMed  Google Scholar 

  109. Johnson, J. A., Fried, S. K., Pi-Sunyer, F. X. & Albu, J. B. Impaired insulin action in subcutaneous adipocytes from women with visceral obesity. Am. J. Physiol. Endocrinol. Metab. 280, E40–E49 (2001).

    CAS  PubMed  Google Scholar 

  110. Michaud, A. et al. Abdominal adipocyte populations in women with visceral obesity. Eur. J. Endocrinol. 174, 227–239 (2016).

    CAS  PubMed  Google Scholar 

  111. Veilleux, A., Caron-Jobin, M., Noel, S., Laberge, P. Y. & Tchernof, A. Visceral adipocyte hypertrophy is associated with dyslipidemia independent of body composition and fat distribution in women. Diabetes 60, 1504–1511 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Verboven, K. et al. Abdominal subcutaneous and visceral adipocyte size, lipolysis and inflammation relate to insulin resistance in male obese humans. Sci. Rep. 8, 4677 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Uranga, A. P., Levine, J. & Jensen, M. Isotope tracer measures of meal fatty acid metabolism: reproducibility and effects of the menstrual cycle. Am. J. Physiol. Endocrinol. Metab. 288, E547–E555 (2005).

    CAS  PubMed  Google Scholar 

  114. Romanski, S. A., Nelson, R. M. & Jensen, M. D. Meal fatty acid uptake in adipose tissue: gender effects in nonobese humans. Am. J. Physiol. Endocrinol. Metab. 279, E455–E462 (2000).

    CAS  PubMed  Google Scholar 

  115. Votruba, S. B. & Jensen, M. D. Sex-specific differences in leg fat uptake are revealed with a high-fat meal. Am. J. Physiol. Endocrinol. Metab. 291, E1115–E1123 (2006).

    CAS  PubMed  Google Scholar 

  116. Votruba, S. B. & Jensen, M. D. Sex differences in abdominal, gluteal, and thigh LPL activity. Am. J. Physiol. Endocrinol. Metab. 292, E1823–E1828 (2007).

    CAS  PubMed  Google Scholar 

  117. Santosa, S., Hensrud, D. D., Votruba, S. B. & Jensen, M. D. The influence of sex and obesity phenotype on meal fatty acid metabolism before and after weight loss. Am. J. Clin. Nutr. 88, 1134–1141 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Nguyen, T. T., Hernandez Mijares, A., Johnson, C. M. & Jensen, M. D. Postprandial leg and splanchnic fatty acid metabolism in nonobese men and women. Am. J. Physiol. 271, E965–E972 (1996).

    CAS  PubMed  Google Scholar 

  119. Fried, S. K. & Kral, J. G. Sex differences in regional distribution of fat cell size and lipoprotein lipase activity in morbidly obese patients. Int. J. Obes. 11, 129–140 (1987).

    CAS  PubMed  Google Scholar 

  120. Edens, N. K., Fried, S. K., Kral, J. G., Hirsch, J. & Leibel, R. L. In vitro lipid synthesis in human adipose tissue from three abdominal sites. Am. J. Physiol. 265, E374–E379 (1993).

    CAS  PubMed  Google Scholar 

  121. Macotela, Y., Boucher, J., Tran, T. T. & Kahn, C. R. Sex and depot differences in adipocyte insulin sensitivity and glucose metabolism. Diabetes 58, 803–812 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Homma, H. et al. Estrogen suppresses transcription of lipoprotein lipase gene. Existence of a unique estrogen response element on the lipoprotein lipase promoter. J. Biol. Chem. 275, 11404–11411 (2000).

    CAS  PubMed  Google Scholar 

  123. Pedersen, S. B., Kristensen, K., Hermann, P. A., Katzenellenbogen, J. A. & Richelsen, B. Estrogen controls lipolysis by up-regulating α2A-adrenergic receptors directly in human adipose tissue through the estrogen receptor α. Implications for the female fat distribution. J. Clin. Endocrinol. Metab. 89, 1869–1878 (2004).

    CAS  PubMed  Google Scholar 

  124. Price, T. M. et al. Estrogen regulation of adipose tissue lipoprotein lipase–possible mechanism of body fat distribution. Am. J. Obstet. Gynecol. 178, 101–107 (1998).

    CAS  PubMed  Google Scholar 

  125. D’Eon, T. M. et al. Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. J. Biol. Chem. 280, 35983–35991 (2005).

    PubMed  Google Scholar 

  126. Lundholm, L. et al. Key lipogenic gene expression can be decreased by estrogen in human adipose tissue. Fertil. Steril. 90, 44–48 (2008).

    CAS  PubMed  Google Scholar 

  127. Shadid, S., Koutsari, C. & Jensen, M. D. Direct free fatty acid uptake into human adipocytes in vivo: relation to body fat distribution. Diabetes 56, 1369–1375 (2007).

    CAS  PubMed  Google Scholar 

  128. McQuaid, S. E. et al. Femoral adipose tissue may accumulate the fat that has been recycled as VLDL and nonesterified fatty acids. Diabetes 59, 2465–2473 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Koutsari, C., Mundi, M. S., Ali, A. H. & Jensen, M. D. Storage rates of circulating free fatty acid into adipose tissue during eating or walking in humans. Diabetes 61, 329–338 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Kusminski, C. M. & Scherer, P. E. Mitochondrial dysfunction in white adipose tissue. Trends Endocrinol. Metab. 23, 435–443 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Rodriguez-Cuenca, S. et al. Sex-dependent thermogenesis, differences in mitochondrial morphology and function, and adrenergic response in brown adipose tissue. J. Biol. Chem. 277, 42958–42963 (2002).

    CAS  PubMed  Google Scholar 

  132. Nookaew, I. et al. Adipose tissue resting energy expenditure and expression of genes involved in mitochondrial function are higher in women than in men. J. Clin. Endocrinol. Metab. 98, E370–E378 (2013).

    CAS  PubMed  Google Scholar 

  133. Karpe, F., Dickmann, J. R. & Frayn, K. N. Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes 60, 2441–2449 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Browning, J. D., Baxter, J., Satapati, S. & Burgess, S. C. The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men. J. Lipid Res. 53, 577–586 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Merimee, T. J., Misbin, R. I. & Pulkkinen, A. J. Sex variations in free fatty acids and ketones during fasting: evidence for a role of glucagon. J. Clin. Endocrinol. Metab. 46, 414–419 (1978).

    CAS  PubMed  Google Scholar 

  136. Jensen, M. D. & Johnson, C. M. Contribution of leg and splanchnic free fatty acid (FFA) kinetics to postabsorptive FFA flux in men and women. Metabolism 45, 662–666 (1996).

    CAS  PubMed  Google Scholar 

  137. Horton, T. J., Dow, S., Armstrong, M. & Donahoo, W. T. Greater systemic lipolysis in women compared with men during moderate-dose infusion of epinephrine and/or norepinephrine. J. Appl. Physiol. 107, 200–210 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Mittendorfer, B., Patterson, B. W. & Klein, S. Effect of sex and obesity on basal VLDL-triacylglycerol kinetics. Am. J. Clin. Nutr. 77, 573–579 (2003).

    CAS  PubMed  Google Scholar 

  139. Mittendorfer, B., Magkos, F., Fabbrini, E., Mohammed, B. S. & Klein, S. Relationship between body fat mass and free fatty acid kinetics in men and women. Obesity 17, 1872–1877 (2009).

    CAS  PubMed  Google Scholar 

  140. Nielsen, S. et al. Energy expenditure, sex, and endogenous fuel availability in humans. J. Clin. Invest. 111, 981–988 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Jensen, M. D. Gender differences in regional fatty acid metabolism before and after meal ingestion. J. Clin. Invest. 96, 2297–2303 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Guo, Z., Hensrud, D. D., Johnson, C. M. & Jensen, M. D. Regional postprandial fatty acid metabolism in different obesity phenotypes. Diabetes 48, 1586–1592 (1999).

    CAS  PubMed  Google Scholar 

  143. Lonnqvist, F., Thorne, A., Large, V. & Arner, P. Sex differences in visceral fat lipolysis and metabolic complications of obesity. Arterioscler. Thromb. Vasc. Biol. 17, 1472–1480 (1997).

    CAS  PubMed  Google Scholar 

  144. Rebuffe-Scrive, M., Andersson, B., Olbe, L. & Bjorntorp, P. Metabolism of adipose tissue in intraabdominal depots of nonobese men and women. Metabolism 38, 453–458 (1989).

    CAS  PubMed  Google Scholar 

  145. Jensen, M. D., Cryer, P. E., Johnson, C. M. & Murray, M. J. Effects of epinephrine on regional free fatty acid and energy metabolism in men and women. Am. J. Physiol. 270, E259–E264 (1996).

    CAS  PubMed  Google Scholar 

  146. Horton, T. J., Pagliassotti, M. J., Hobbs, K. & Hill, J. O. Fuel metabolism in men and women during and after long-duration exercise. J. Appl. Physiol. 85, 1823–1832 (1998).

    CAS  PubMed  Google Scholar 

  147. Arner, P., Kriegholm, E., Engfeldt, P. & Bolinder, J. Adrenergic regulation of lipolysis in situ at rest and during exercise. J. Clin. Invest. 85, 893–898 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Burguera, B. et al. Leg free fatty acid kinetics during exercise in men and women. Am. J. Physiol. Endocrinol. Metab. 278, E113–E117 (2000).

    CAS  PubMed  Google Scholar 

  149. Schmidt, S. L. et al. Adrenergic control of lipolysis in women compared with men. J. Appl. Physiol. 117, 1008–1019 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Wahrenberg, H., Lonnqvist, F. & Arner, P. Mechanisms underlying regional differences in lipolysis in human adipose tissue. J. Clin. Invest. 84, 458–467 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Ryden, M., Gao, H. & Arner, P. Influence of aging and menstrual status on subcutaneous fat cell lipolysis. J. Clin. Endocrinol. Metab. 105, dgz245 (2020).

    PubMed  Google Scholar 

  152. Samaras, K., Botelho, N. K., Chisholm, D. J. & Lord, R. V. Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity 18, 884–889 (2010).

    CAS  PubMed  Google Scholar 

  153. Linder, K., Arner, P., Flores-Morales, A., Tollet-Egnell, P. & Norstedt, G. Differentially expressed genes in visceral or subcutaneous adipose tissue of obese men and women. J. Lipid Res. 45, 148–154 (2004).

    CAS  PubMed  Google Scholar 

  154. Vohl, M. C. et al. A survey of genes differentially expressed in subcutaneous and visceral adipose tissue in men. Obes. Res. 12, 1217–1222 (2004).

    CAS  PubMed  Google Scholar 

  155. Vidal, H. Gene expression in visceral and subcutaneous adipose tissues. Ann. Med. 33, 547–555 (2001).

    CAS  PubMed  Google Scholar 

  156. Lefebvre, A. M. et al. Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes 47, 98–103 (1998).

    CAS  PubMed  Google Scholar 

  157. Montague, C. T. et al. Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes 47, 1384–1391 (1998).

    CAS  PubMed  Google Scholar 

  158. Fried, S. K., Bunkin, D. A. & Greenberg, A. S. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J. Clin. Endocrinol. Metab. 83, 847–850 (1998).

    CAS  PubMed  Google Scholar 

  159. Vasconcelos, R. P. et al. Sex differences in subcutaneous adipose tissue redox homeostasis and inflammation markers in control and high-fat diet fed rats. Appl. Physiol. Nutr. Metab. 44, 720–726 (2019).

    CAS  PubMed  Google Scholar 

  160. Griffin, C., Lanzetta, N., Eter, L. & Singer, K. Sexually dimorphic myeloid inflammatory and metabolic responses to diet-induced obesity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 311, R211–R216 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Davis, K. E. et al. The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis. Mol. Metab. 2, 227–242 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Kosteli, A. et al. Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. J. Clin. Invest. 120, 3466–3479 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Varghese, M. et al. Sex differences in inflammatory responses to adipose tissue lipolysis in diet-induced obesity. Endocrinology 160, 293–312 (2019).

    CAS  PubMed  Google Scholar 

  164. Demerath, E. W. et al. Serum leptin concentration, body composition, and gonadal hormones during puberty. Int. J. Obes. Relat. Metab. Disord. 23, 678–685 (1999).

    CAS  PubMed  Google Scholar 

  165. Havel, P. J., Kasim-Karakas, S., Dubuc, G. R., Mueller, W. & Phinney, S. D. Gender differences in plasma leptin concentrations. Nat. Med. 2, 949–950 (1996).

    CAS  PubMed  Google Scholar 

  166. Pineiro, V. et al. Dihydrotestosterone, stanozolol, androstenedione and dehydroepiandrosterone sulphate inhibit leptin secretion in female but not in male samples of omental adipose tissue in vitro: lack of effect of testosterone. J. Endocrinol. 160, 425–432 (1999).

    CAS  PubMed  Google Scholar 

  167. Casabiell, X. et al. Gender differences in both spontaneous and stimulated leptin secretion by human omental adipose tissue in vitro: dexamethasone and estradiol stimulate leptin release in women, but not in men. J. Clin. Endocrinol. Metab. 83, 2149–2155 (1998).

    CAS  PubMed  Google Scholar 

  168. Rosenbaum, M. et al. Effects of gender, body composition, and menopause on plasma concentrations of leptin. J. Clin. Endocrinol. Metab. 81, 3424–3427 (1996).

    CAS  PubMed  Google Scholar 

  169. Steinberg, G. R., Rush, J. W. & Dyck, D. J. AMPK expression and phosphorylation are increased in rodent muscle after chronic leptin treatment. Am. J. Physiol. Endocrinol. Metab. 284, E648–E654 (2003).

    CAS  PubMed  Google Scholar 

  170. Petersen, K. F. et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J. Clin. Invest. 109, 1345–1350 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Hoeg, L. D. et al. Adiponectin concentration is associated with muscle insulin sensitivity, AMPK phosphorylation, and ceramide content in skeletal muscles of men but not women. J. Appl. Physiol. 114, 592–601 (2013).

    CAS  PubMed  Google Scholar 

  172. Salas-Salvado, J. et al. Plasma adiponectin distribution in a Mediterranean population and its association with cardiovascular risk factors and metabolic syndrome. Metabolism 56, 1486–1492 (2007).

    CAS  PubMed  Google Scholar 

  173. Cnop, M. et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 46, 459–469 (2003).

    CAS  PubMed  Google Scholar 

  174. Yamamoto, Y. et al. Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japanese population. Clin. Sci. 103, 137–142 (2002).

    CAS  Google Scholar 

  175. Xu, A. et al. Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. J. Biol. Chem. 280, 18073–18080 (2005).

    CAS  PubMed  Google Scholar 

  176. Ouchi, N. & Walsh, K. Adiponectin as an anti-inflammatory factor. Clin. Chim. Acta 380, 24–30 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  177. Combs, T. P. et al. Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes 52, 268–276 (2003).

    CAS  PubMed  Google Scholar 

  178. Pinnick, K. E. et al. Gluteofemoral adipose tissue plays a major role in production of the lipokine palmitoleate in humans. Diabetes 61, 1399–1403 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Lundsgaard, A. M. & Kiens, B. Gender differences in skeletal muscle substrate metabolism – molecular mechanisms and insulin sensitivity. Front. Endocrinol. 5, 195 (2014).

    Google Scholar 

  180. Paula, F. J. et al. Sex-related differences in peripheral glucose metabolism in normal subjects. Diabete Metab. 16, 234–239 (1990).

    CAS  PubMed  Google Scholar 

  181. Desmeules, A. et al. Post-heparin lipolytic enzyme activities, sex hormones and sex hormone-binding globulin (SHBG) in men and women: the HERITAGE family study. Atherosclerosis 171, 343–350 (2003).

    CAS  PubMed  Google Scholar 

  182. Kiens, B. et al. Lipid-binding proteins and lipoprotein lipase activity in human skeletal muscle: influence of physical activity and gender. J. Appl. Physiol. 97, 1209–1218 (2004).

    CAS  PubMed  Google Scholar 

  183. Smith, I. J., Huffman, K. M., Durheim, M. T., Duscha, B. D. & Kraus, W. E. Sex-specific alterations in mRNA level of key lipid metabolism enzymes in skeletal muscle of overweight and obese subjects following endurance exercise. Physiol. Genomics 36, 149–157 (2009).

    CAS  PubMed  Google Scholar 

  184. Ellis, G. S., Lanza-Jacoby, S., Gow, A. & Kendrick, Z. V. Effects of estradiol on lipoprotein lipase activity and lipid availability in exercised male rats. J. Appl. Physiol. 77, 209–215 (1994).

    CAS  PubMed  Google Scholar 

  185. Fu, M. H., Maher, A. C., Hamadeh, M. J., Ye, C. & Tarnopolsky, M. A. Exercise, sex, menstrual cycle phase, and 17β-estradiol influence metabolism-related genes in human skeletal muscle. Physiol. Genomics 40, 34–47 (2009).

    CAS  PubMed  Google Scholar 

  186. Devries, M. C., Lowther, S. A., Glover, A. W., Hamadeh, M. J. & Tarnopolsky, M. A. IMCL area density, but not IMCL utilization, is higher in women during moderate-intensity endurance exercise, compared with men. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293, R2336–R2342 (2007).

    CAS  PubMed  Google Scholar 

  187. Tarnopolsky, M. A. et al. Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, R1271–R1278 (2007).

    CAS  PubMed  Google Scholar 

  188. Roepstorff, C. et al. Sex differences in hormone-sensitive lipase expression, activity, and phosphorylation in skeletal muscle at rest and during exercise. Am. J. Physiol. Endocrinol. Metab. 291, E1106–E1114 (2006).

    CAS  PubMed  Google Scholar 

  189. Steffensen, C. H., Roepstorff, C., Madsen, M. & Kiens, B. Myocellular triacylglycerol breakdown in females but not in males during exercise. Am. J. Physiol. Endocrinol. Metab. 282, E634–E642 (2002).

    CAS  PubMed  Google Scholar 

  190. Roepstorff, C. et al. Gender differences in substrate utilization during submaximal exercise in endurance-trained subjects. Am. J. Physiol. Endocrinol. Metab. 282, E435–E447 (2002).

    CAS  PubMed  Google Scholar 

  191. Tarnopolsky, M. A. Sex differences in exercise metabolism and the role of 17-beta estradiol. Med. Sci. Sports Exerc. 40, 648–654 (2008).

    CAS  PubMed  Google Scholar 

  192. Goodpaster, B. H., He, J., Watkins, S. & Kelley, D. E. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J. Clin. Endocrinol. Metab. 86, 5755–5761 (2001).

    CAS  PubMed  Google Scholar 

  193. Essen, B., Jansson, E., Henriksson, J., Taylor, A. W. & Saltin, B. Metabolic characteristics of fibre types in human skeletal muscle. Acta Physiol. Scand. 95, 153–165 (1975).

    CAS  PubMed  Google Scholar 

  194. Roepstorff, C. et al. Higher skeletal muscle α2AMPK activation and lower energy charge and fat oxidation in men than in women during submaximal exercise. J. Physiol. 574, 125–138 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  195. Ribas, V. et al. Skeletal muscle action of estrogen receptor α is critical for the maintenance of mitochondrial function and metabolic homeostasis in females. Sci. Transl Med. 8, 334ra54 (2016).

    PubMed  PubMed Central  Google Scholar 

  196. Moro, C. et al. Influence of gender, obesity, and muscle lipase activity on intramyocellular lipids in sedentary individuals. J. Clin. Endocrinol. Metab. 94, 3440–3447 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  197. Peters, S. J. et al. Perilipin family (PLIN) proteins in human skeletal muscle: the effect of sex, obesity, and endurance training. Appl. Physiol. Nutr. Metab. 37, 724–735 (2012).

    CAS  PubMed  Google Scholar 

  198. Covington, J. D. et al. Skeletal muscle perilipin 3 and coatomer proteins are increased following exercise and are associated with fat oxidation. PLoS ONE 9, e91675 (2014).

    PubMed  PubMed Central  Google Scholar 

  199. Granneman, J. G., Moore, H. P., Mottillo, E. P., Zhu, Z. & Zhou, L. Interactions of perilipin-5 (Plin5) with adipose triglyceride lipase. J. Biol. Chem. 286, 5126–5135 (2011).

    CAS  PubMed  Google Scholar 

  200. Wang, H. et al. Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria. J. Lipid Res. 52, 2159–2168 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  201. Koutsari, C. et al. Nonoxidative free fatty acid disposal is greater in young women than men. J. Clin. Endocrinol. Metab. 96, 541–547 (2011).

    CAS  PubMed  Google Scholar 

  202. Levadoux, E. et al. Reduced whole-body fat oxidation in women and in the elderly. Int. J. Obes. Relat. Metab. Disord. 25, 39–44 (2001).

    CAS  PubMed  Google Scholar 

  203. Barros, R. P., Machado, U. F., Warner, M. & Gustafsson, J. A. Muscle GLUT4 regulation by estrogen receptors ERβ and ERα. Proc. Natl Acad. Sci. USA 103, 1605–1608 (2006).

    CAS  PubMed  Google Scholar 

  204. Bryzgalova, G. et al. Evidence that oestrogen receptor-α plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver. Diabetologia 49, 588–597 (2006).

    CAS  PubMed  Google Scholar 

  205. Dieli-Conwright, C. M., Spektor, T. M., Rice, J. C. & Todd Schroeder, E. Oestradiol and SERM treatments influence oestrogen receptor coregulator gene expression in human skeletal muscle cells. Acta Physiol. 197, 187–196 (2009).

    CAS  Google Scholar 

  206. Ordonez, P. et al. 17β-Estradiol and/or progesterone protect from insulin resistance in STZ-induced diabetic rats. J. Steroid Biochem. Mol. Biol. 111, 287–294 (2008).

    CAS  PubMed  Google Scholar 

  207. Riant, E. et al. Estrogens protect against high-fat diet-induced insulin resistance and glucose intolerance in mice. Endocrinology 150, 2109–2117 (2009).

    CAS  PubMed  Google Scholar 

  208. Ribas, V. et al. Impaired oxidative metabolism and inflammation are associated with insulin resistance in ERα-deficient mice. Am. J. Physiol. Endocrinol. Metab. 298, E304–E319 (2010).

    CAS  PubMed  Google Scholar 

  209. Rogers, N. H., Witczak, C. A., Hirshman, M. F., Goodyear, L. J. & Greenberg, A. S. Estradiol stimulates Akt, AMP-activated protein kinase (AMPK) and TBC1D1/4, but not glucose uptake in rat soleus. Biochem. Biophys. Res. Commun. 382, 646–650 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  210. Salehzadeh, F., Rune, A., Osler, M. & Al-Khalili, L. Testosterone or 17β-estradiol exposure reveals sex-specific effects on glucose and lipid metabolism in human myotubes. J. Endocrinol. 210, 219–229 (2011).

    CAS  PubMed  Google Scholar 

  211. Hevener, A. L., Zhou, Z., Moore, T. M., Drew, B. G. & Ribas, V. The impact of ERα action on muscle metabolism and insulin sensitivity – strong enough for a man, made for a woman. Mol. Metab. 15, 20–34 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  212. Venables, M. C., Achten, J. & Jeukendrup, A. E. Determinants of fat oxidation during exercise in healthy men and women: a cross-sectional study. J. Appl. Physiol. 98, 160–167 (2005).

    PubMed  Google Scholar 

  213. Cheneviere, X., Borrani, F., Sangsue, D., Gojanovic, B. & Malatesta, D. Gender differences in whole-body fat oxidation kinetics during exercise. Appl. Physiol. Nutr. Metab. 36, 88–95 (2011).

    CAS  PubMed  Google Scholar 

  214. Haugaard, S. B., Madsbad, S., Mu, H. & Vaag, A. Desaturation of excess intramyocellular triacylglycerol in obesity: implications for glycemic control. Int. J. Obes. 34, 500–510 (2010).

    CAS  Google Scholar 

  215. Warensjo, E., Ohrvall, M. & Vessby, B. Fatty acid composition and estimated desaturase activities are associated with obesity and lifestyle variables in men and women. Nutr. Metab. Cardiovasc. Dis. 16, 128–136 (2006).

    PubMed  Google Scholar 

  216. Rune, A. et al. Evidence against a sexual dimorphism in glucose and fatty acid metabolism in skeletal muscle cultures from age-matched men and post-menopausal women. Acta Physiol. 197, 207–215 (2009).

    CAS  Google Scholar 

  217. Eichmann, T. O. et al. Studies on the substrate and stereo/regioselectivity of adipose triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O-acyltransferases. J. Biol. Chem. 287, 41446–41457 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  218. Berthon, P. M., Howlett, R. A., Heigenhauser, G. J. & Spriet, L. L. Human skeletal muscle carnitine palmitoyltransferase I activity determined in isolated intact mitochondria. J. Appl. Physiol. 85, 148–153 (1998).

    CAS  PubMed  Google Scholar 

  219. Costill, D. L., Fink, W. J., Getchell, L. H., Ivy, J. L. & Witzmann, F. A. Lipid metabolism in skeletal muscle of endurance-trained males and females. J. Appl. Physiol. Respir. Env. Exerc. Physiol. 47, 787–791 (1979).

    CAS  Google Scholar 

  220. Nye, G. A., Sakellariou, G. K., Degens, H. & Lightfoot, A. P. Muscling in on mitochondrial sexual dimorphism; role of mitochondrial dimorphism in skeletal muscle health and disease. Clin. Sci. 131, 1919–1922 (2017).

    Google Scholar 

  221. Miotto, P. M., McGlory, C., Holloway, T. M., Phillips, S. M. & Holloway, G. P. Sex differences in mitochondrial respiratory function in human skeletal muscle. Am. J. Physiol. Regul. Integr. Comp. Physiol. 314, R909–R915 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  222. Milanesi, L., Russo de Boland, A. & Boland, R. Expression and localization of estrogen receptor α in the C2C12 murine skeletal muscle cell line. J. Cell Biochem. 104, 1254–1273 (2008).

    CAS  PubMed  Google Scholar 

  223. Campbell, S. E., Mehan, K. A., Tunstall, R. J., Febbraio, M. A. & Cameron-Smith, D. 17beta-estradiol upregulates the expression of peroxisome proliferator-activated receptor alpha and lipid oxidative genes in skeletal muscle. J. Mol. Endocrinol. 31, 37–45 (2003).

    CAS  PubMed  Google Scholar 

  224. Maher, A. C., Akhtar, M. & Tarnopolsky, M. A. Men supplemented with 17β-estradiol have increased β-oxidation capacity in skeletal muscle. Physiol. Genomics 42, 342–347 (2010).

    CAS  PubMed  Google Scholar 

  225. Gordon, T., Kannel, W. B., Hjortland, M. C. & McNamara, P. M. Menopause and coronary heart disease. The Framingham Study. Ann. Intern. Med. 89, 157–161 (1978).

    CAS  PubMed  Google Scholar 

  226. Liu, Y. et al. Adiponectin corrects high-fat diet-induced disturbances in muscle metabolomic profile and whole-body glucose homeostasis. Diabetes 62, 743–752 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  227. Yamauchi, T. et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med. 8, 1288–1295 (2002).

    CAS  PubMed  Google Scholar 

  228. Yamauchi, T. et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 7, 941–946 (2001).

    CAS  PubMed  Google Scholar 

  229. Tomas, E. et al. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc. Natl Acad. Sci. USA 99, 16309–16313 (2002).

    CAS  PubMed  Google Scholar 

  230. van der Kolk, B. W. et al. Plasma lipid profiling of tissue-specific insulin resistance in human obesity. Int. J. Obes. 43, 989–998 (2019).

    Google Scholar 

  231. Ter Horst, K. W. et al. Sexual dimorphism in hepatic, adipose tissue, and peripheral tissue insulin sensitivity in obese humans. Front. Endocrinol. 6, 182 (2015).

    Google Scholar 

  232. Vogelzangs, N. et al. Metabolic profiling of tissue-specific insulin resistance in human obesity: results from the Diogenes study and the Maastricht study. Int. J. Obes. 44, 1376–1386 (2020).

    CAS  Google Scholar 

  233. Vernon, G., Baranova, A. & Younossi, Z. M. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment. Pharmacol. Ther. 34, 274–285 (2011).

    CAS  PubMed  Google Scholar 

  234. Power, M. L. & Schulkin, J. Sex differences in fat storage, fat metabolism, and the health risks from obesity: possible evolutionary origins. Br. J. Nutr. 99, 931–940 (2008).

    CAS  PubMed  Google Scholar 

  235. Browning, J. D. et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40, 1387–1395 (2004).

    PubMed  Google Scholar 

  236. de Alwis, N. M. & Day, C. P. Non-alcoholic fatty liver disease: the mist gradually clears. J. Hepatol. 48, S104–S112 (2008).

    PubMed  Google Scholar 

  237. Clark, J. M., Brancati, F. L. & Diehl, A. M. Nonalcoholic fatty liver disease. Gastroenterology 122, 1649–1657 (2002).

    Google Scholar 

  238. McKenzie, J. et al. Effects of HRT on liver enzyme levels in women with type 2 diabetes: a randomized placebo-controlled trial. Clin. Endocrinol. 65, 40–44 (2006).

    CAS  Google Scholar 

  239. Galmes-Pascual, B. M. et al. 17β-estradiol improves hepatic mitochondrial biogenesis and function through PGC1B. J. Endocrinol. 232, 297–308 (2017).

    CAS  PubMed  Google Scholar 

  240. Zhu, L. et al. Estrogen treatment after ovariectomy protects against fatty liver and may improve pathway-selective insulin resistance. Diabetes 62, 424–434 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  241. Zhu, L., Martinez, M. N., Emfinger, C. H., Palmisano, B. T. & Stafford, J. M. Estrogen signaling prevents diet-induced hepatic insulin resistance in male mice with obesity. Am. J. Physiol. Endocrinol. Metab. 306, E1188–E1197 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  242. Marinou, K. et al. Young women partition fatty acids towards ketone body production rather than VLDL-TAG synthesis, compared with young men. Br. J. Nutr. 105, 857–865 (2011).

    CAS  PubMed  Google Scholar 

  243. Halkes, C. J. et al. Gender differences in postprandial ketone bodies in normolipidemic subjects and in untreated patients with familial combined hyperlipidemia. Arterioscler. Thromb. Vasc. Biol. 23, 1875–1880 (2003).

    CAS  PubMed  Google Scholar 

  244. Hodson, L. et al. The contribution of splanchnic fat to VLDL triglyceride is greater in insulin-resistant than insulin-sensitive men and women: studies in the postprandial state. Diabetes 56, 2433–2441 (2007).

    CAS  PubMed  Google Scholar 

  245. Pramfalk, C. et al. Sex-specific differences in hepatic fat oxidation and synthesis may explain the higher propensity for NAFLD in men. J. Clin. Endocrinol. Metab. 100, 4425–4433 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  246. Santosa, S. & Jensen, M. D. The sexual dimorphism of lipid kinetics in humans. Front. Endocrinol. 6, 103 (2015).

    Google Scholar 

  247. Gormsen, L. C. et al. Energy expenditure, insulin, and VLDL-triglyceride production in humans. J. Lipid Res. 47, 2325–2332 (2006).

    CAS  PubMed  Google Scholar 

  248. Magkos, F. et al. Estrogen deficiency after menopause does not result in male very-low-density lipoprotein metabolism phenotype. J. Clin. Endocrinol. Metab. 95, 3377–3384 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  249. Arita, Y. et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem. Biophys. Res. Commun. 257, 79–83 (1999).

    CAS  PubMed  Google Scholar 

  250. Combs, T. P., Berg, A. H., Obici, S., Scherer, P. E. & Rossetti, L. Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J. Clin. Invest. 108, 1875–1881 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  251. Tishinsky, J. M., Robinson, L. E. & Dyck, D. J. Insulin-sensitizing properties of adiponectin. Biochimie 94, 2131–2136 (2012).

    CAS  PubMed  Google Scholar 

  252. Garaulet, M., Perex-Llamas, F., Fuente, T., Zamora, S. & Tebar, F. J. Anthropometric, computed tomography and fat cell data in an obese population: relationship with insulin, leptin, tumor necrosis factor-alpha, sex hormone-binding globulin and sex hormones. Eur. J. Endocrinol. 143, 657–666 (2000).

    CAS  PubMed  Google Scholar 

  253. Yadav, A., Kataria, M. A., Saini, V. & Yadav, A. Role of leptin and adiponectin in insulin resistance. Clin. Chim. Acta 417, 80–84 (2013).

    CAS  PubMed  Google Scholar 

  254. Kim, S. H. & Reaven, G. Sex differences in insulin resistance and cardiovascular disease risk. J. Clin. Endocrinol. Metab. 98, E1716–E1721 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  255. Soldin, O. P. & Mattison, D. R. Sex differences in pharmacokinetics and pharmacodynamics. Clin. Pharmacokinet. 48, 143–157 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  256. Christensen, P. et al. Men and women respond differently to rapid weight loss: metabolic outcomes of a multi-centre intervention study after a low-energy diet in 2500 overweight, individuals with pre-diabetes (PREVIEW). Diabetes Obes. Metab. 20, 2840–2851 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  257. Ramos-Lopez, O. et al. Modeling of an integrative prototype based on genetic, phenotypic, and environmental information for personalized prescription of energy-restricted diets in overweight/obese subjects. Am. J. Clin. Nutr. 111, 459–470 (2019).

    Google Scholar 

  258. Bray, G. A. et al. Markers of dietary protein intake are associated with successful weight loss in the POUNDS Lost trial. Clin. Obes. 7, 166–175 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  259. Navas-Carretero, S. et al. The impact of gender and protein intake on the success of weight maintenance and associated cardiovascular risk benefits, independent of the mode of food provision: the DiOGenes randomized trial. J. Am. Coll. Nutr. 35, 20–30 (2016).

    CAS  PubMed  Google Scholar 

  260. Berger, S. E., Huggins, G. S., McCaffery, J. M., Jacques, P. F. & Lichtenstein, A. H. Change in cardiometabolic risk factors associated with magnitude of weight regain 3 years after a 1-year intensive lifestyle intervention in type 2 diabetes mellitus: the Look AHEAD trial. J. Am. Heart Assoc. 8, e010951 (2019).

    PubMed  PubMed Central  Google Scholar 

  261. Bedard, A., Corneau, L., Lamarche, B., Dodin, S. & Lemieux, S. Sex differences in the impact of the Mediterranean diet on LDL particle size distribution and oxidation. Nutrients 7, 3705–3723 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  262. Bedard, A., Riverin, M., Dodin, S., Corneau, L. & Lemieux, S. Sex differences in the impact of the Mediterranean diet on cardiovascular risk profile. Br. J. Nutr. 108, 1428–1434 (2012).

    CAS  PubMed  Google Scholar 

  263. Bedard, A. et al. Effects of the traditional Mediterranean diet on adiponectin and leptin concentrations in men and premenopausal women: do sex differences exist? Eur. J. Clin. Nutr. 68, 561–566 (2014).

    CAS  PubMed  Google Scholar 

  264. Leblanc, V. et al. Gender differences in the long-term effects of a nutritional intervention program promoting the Mediterranean diet: changes in dietary intakes, eating behaviors, anthropometric and metabolic variables. Nutr. J. 13, 107 (2014).

    PubMed  PubMed Central  Google Scholar 

  265. Hjorth, M. F. et al. Pretreatment fasting glucose and insulin as determinants of weight loss on diets varying in macronutrients and dietary fibers–the POUNDS LOST study. Nutrients 11, 586 (2019).

    CAS  PubMed Central  Google Scholar 

  266. Hjorth, M. F., Due, A., Larsen, T. M. & Astrup, A. Pretreatment fasting plasma glucose modifies dietary weight loss maintenance success: results from a stratified RCT. Obesity 25, 2045–2048 (2017).

    CAS  PubMed  Google Scholar 

  267. Hjorth, M. F. et al. Pretreatment fasting plasma glucose and insulin modify dietary weight loss success: results from 3 randomized clinical trials. Am. J. Clin. Nutr. 106, 499–505 (2017).

    CAS  PubMed  Google Scholar 

  268. Blanco-Rojo, R. et al. The insulin resistance phenotype (muscle or liver) interacts with the type of diet to determine changes in disposition index after 2 years of intervention: the CORDIOPREV-DIAB randomised clinical trial. Diabetologia 59, 67–76 (2016).

    CAS  PubMed  Google Scholar 

  269. Tierney, A. C. et al. Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome–LIPGENE: a European randomized dietary intervention study. Int. J. Obes. 35, 800–809 (2011).

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, Netherlands

    Gijs H. Goossens, Johan W. E. Jocken & Ellen E. Blaak

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  1. Gijs H. Goossens
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Glossary

Obesity

Abnormal or excessive adipose accumulation, also called adiposity, that presents a risk to health; a crude measure of obesity is the BMI, with a BMI ≥25 kg/m2 considered overweight, and a BMI ≥30 kg/m2 defined as obesity.

Insulin resistance

A diminished ability of cells to respond to the physiological action of insulin.

BMI

A person’s weight (in kilograms) divided by the square of their height (in metres).

Subcutaneous adipose tissue

Adipose tissue stored directly underneath the skin.

Visceral adipose tissue

Adipose tissue dispersed between the abdominal organs (intra-abdominal adipose tissue).

Lower body adipose tissue

Adipose tissue stored in the legs and around the hips, including femoral and gluteal adipose tissue.

Ectopic lipid deposition

Storage of lipids in tissues other than adipose tissue, which normally contain only small amounts of lipids such as the liver, skeletal muscle, pancreas and heart.

Preadipocytes

Adipose tissue progenitor cells with a fibroblastic appearance that are committed to adipocyte cell fate and express early markers of adipocyte differentiation.

Adipogenic potential

The capacity of adipose progenitor cells to differentiate into mature adipocytes (adipogenesis).

Femoral adipose tissue

Subcutaneous adipose tissue stored in the upper leg and/or thighs.

Abdominal adipose tissue

Adipose tissue stored in and around the abdomen.

Gluteal subcutaneous adipose tissue

Subcutaneous adipose tissue stored in the buttocks and/or hips.

Lipolysis

The breakdown of triacylglycerol and other lipids by hydrolysis to fatty acids and glycerol.

Upper body adipose tissue

Adipose tissue stored in the abdominal and trunk region, including subcutaneous and visceral adipose tissue.

Lipogenesis

The synthesis of fatty acids and triacylglycerol (lipids) from non-lipid precursors.

Adipose tissue expandability

The capacity of adipose tissue to accommodate excess lipid by dynamically changing the number and size of mature adipocytes; the maximum capacity for adipose expansion is determined by genetic and environmental factors, when the maximum capacity is reached, lipid spillover into the circulation contributes to ectopic lipid deposition.

Intramyocellular triacylglycerol content

Lipids stored in intracellular lipid droplets in myocytes (skeletal muscle cells).

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Goossens, G.H., Jocken, J.W.E. & Blaak, E.E. Sexual dimorphism in cardiometabolic health: the role of adipose tissue, muscle and liver. Nat Rev Endocrinol 17, 47–66 (2021). https://doi.org/10.1038/s41574-020-00431-8

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