Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Biology of upper-body and lower-body adipose tissue—link to whole-body phenotypes

Nature Reviews Endocrinology volume 11, pages 90–100 (2015)Cite this article

Subjects

Key Points

  • Upper-body and lower-body fat accumulation exhibits opposing associations with risk of cardiovascular disease and type 2 diabetes mellitus; lower-body fat seems to have a protective role

  • The abdominal fat depots have high lipid turnover and demonstrate a vigorous lipolytic response to stress hormones

  • The gluteofemoral fat depots sequester lipids that would otherwise be destined for ectopic fat depots

  • The characteristic functional differences between adipocytes in the upper body and lower body are probably regulated by site-specific expression of a set of developmental genes that are under epigenetic control

Abstract

The distribution of adipose tissue in the body has wide-ranging and reproducible associations with health and disease. Accumulation of adipose tissue in the upper body (abdominal obesity) is associated with the development of cardiovascular disease, insulin resistance, type 2 diabetes mellitus and even all-cause mortality. Conversely, accumulation of fat in the lower body (gluteofemoral obesity) shows opposite associations with cardiovascular disease and type 2 diabetes mellitus when adjusted for overall fat mass. The abdominal depots are characterized by rapid uptake of predominantly diet-derived fat and a high lipid turnover that is easily stimulated by adrenergic receptor activation. The lower-body fat stores have a reduced lipid turnover with a capacity to accommodate fat undergoing redistribution. Lower-body adipose tissue also seems to retain the capacity to recruit additional adipocytes as a result of weight gain and demonstrates fewer signs of inflammatory insult. New data suggest that the profound functional differences between the upper-body and lower-body tissues are controlled by site-specific sets of developmental genes, such as HOXA6, HOXA5, HOXA3, IRX2 and TBX5 in subcutaneous abdominal adipose tissue and HOTAIR, SHOX2 and HOXC11 in gluteofemoral adipose tissue, which are under epigenetic control. This Review discusses the developmental and functional differences between upper-body and lower-body fat depots and provides mechanistic insight into the disease-protective effects of lower-body fat.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Opposing association between lower-body fat accumulation and metabolically healthy obesity.
Figure 2: Functional differences between adipose tissue depots.

Similar content being viewed by others

References

  1. Snijder, M. B. et al. Independent and opposite associations of waist and hip circumferences with diabetes, hypertension and dyslipidemia: the AusDiab Study. Int. J. Obes. Relat. Metab. Disord. 28, 402–409 (2004).

    CAS  PubMed  Google Scholar 

  2. Yusuf, S. et al. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case–control study. Lancet 366, 1640–1649 (2005).

    PubMed  Google Scholar 

  3. Tchkonia, T. et al. Mechanisms and metabolic implications of regional differences among fat depots. Cell Metab. 17, 644–656 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Wells, J. C. Sexual dimorphism of body composition. Best Pract. Res. Clin. Endocrinol. Metab. 21, 415–430 (2007).

    PubMed  Google Scholar 

  5. Horber, F. F. et al. Altered body fat distribution in patients with glucocorticoid treatment and in patients on long-term dialysis. Am. J. Clin. Nutr. 43, 758–769 (1986).

    CAS  PubMed  Google Scholar 

  6. Stunkard, A. J., Foch, T. T. & Hrubec, Z. A twin study of human obesity. JAMA 256, 51–54 (1986).

    CAS  PubMed  Google Scholar 

  7. Malis, C. et al. Total and regional fat distribution is strongly influenced by genetic factors in young and elderly twins. Obes. Res. 13, 2139–2145 (2005).

    PubMed  Google Scholar 

  8. Lehtovirta, M. et al. Insulin sensitivity and insulin secretion in monozygotic and dizygotic twins. Diabetologia 43, 285–293 (2000).

    CAS  PubMed  Google Scholar 

  9. Agarwal, A. K. & Garg, A. Genetic basis of lipodystrophies and management of metabolic complications. Annu. Rev. Med. 57, 297–311 (2006).

    CAS  PubMed  Google Scholar 

  10. Vigouroux, C., Caron-Debarle, M., Le Dour, C., Magre, J. & Capeau, J. Molecular mechanisms of human lipodystrophies: from adipocyte lipid droplet to oxidative stress and lipotoxicity. Int. J. Biochem. Cell Biol. 43, 862–876 (2011).

    CAS  PubMed  Google Scholar 

  11. 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 

  12. Fox, C. S. et al. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS Genet. 8, e1002695 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. White, U. A. & Tchoukalova, Y. D. Sex dimorphism and depot differences in adipose tissue function. Biochim. Biophys. Acta 1842, 377–392 (2014).

    CAS  PubMed  Google Scholar 

  14. Lee, K. Y. et al. Shox2 is a molecular determinant of depot-specific adipocyte function. Proc. Natl Acad. Sci. USA 110, 11409–11414 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Pinnick, K. E. et al. Distinct developmental profile of lower-body adipose tissue defines resistance against obesity-associated metabolic complications. Diabetes http://dx.doi.org/10.2337/db14-0385.

  16. Bluher, M. Mechanisms in endocrinology: are metabolically healthy obese individuals really healthy? Eur. J. Endocrinol. http://dx.doi.org/10.1530/EJE-14-0540.

  17. Van Vliet-Ostaptchouk, J. V. et al. The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies. BMC Endocr. Disord. 14, 9 (2014).

    PubMed  PubMed Central  Google Scholar 

  18. Stefan, N., Haring, H. U., Hu, F. B. & Schulze, M. B. Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications. Lancet Diabetes Endocrinol. 1, 152–162 (2013).

    PubMed  Google Scholar 

  19. Koster, A. et al. Body fat distribution and inflammation among obese older adults with and without metabolic syndrome. Obesity (Silver Spring) 18, 2354–2361 (2010).

    CAS  Google Scholar 

  20. Appleton, S. L. et al. Diabetes and cardiovascular disease outcomes in the metabolically healthy obese phenotype: a cohort study. Diabetes Care 36, 2388–2394 (2013).

    PubMed  PubMed Central  Google Scholar 

  21. Oxford BioBank [online], (2014).

  22. Kloting, N. et al. Insulin-sensitive obesity. Am. J. Physiol. Endocrinol. Metab. 299, E506–E515 (2010).

    PubMed  Google Scholar 

  23. Danforth, E. Jr. Failure of adipocyte differentiation causes type II diabetes mellitus? Nat. Genet. 26, 13 (2000).

    CAS  PubMed  Google Scholar 

  24. Gray, S. L. & Vidal-Puig, A. J. Adipose tissue expandability in the maintenance of metabolic homeostasis. Nutr. Rev. 65, S7–S12 (2007).

    PubMed  Google Scholar 

  25. Knittle, J. L., Timmers, K., Ginsberg-Fellner, F., Brown, R. E. & Katz, D. P. The growth of adipose tissue in children and adolescents. Cross-sectional and longitudinal studies of adipose cell number and size. J. Clin. Invest. 63, 239–246 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Salans, L. B., Cushman, S. W. & Weismann, R. E. Studies of human adipose tissue. Adipose cell size and number in nonobese and obese patients. J. Clin. Invest. 52, 929–941 (1973).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 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  PubMed Central  Google Scholar 

  28. Spalding, K. L. et al. Dynamics of fat cell turnover in humans. Nature 453, 783–787 (2008).

    CAS  PubMed  Google Scholar 

  29. Billon, N. & Dani, C. Developmental origins of the adipocyte lineage: new insights from genetics and genomics studies. Stem Cell Rev. 8, 55–66 (2012).

    CAS  Google Scholar 

  30. Chau, Y. Y. et al. Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source. Nat. Cell Biol. 16, 367–375 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Billon, N. et al. The generation of adipocytes by the neural crest. Development 134, 2283–2292 (2007).

    CAS  PubMed  Google Scholar 

  32. Tang, W. et al. White fat progenitor cells reside in the adipose vasculature. Science 322, 583–586 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Majka, S. M. et al. De novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific. Proc. Natl Acad. Sci. USA 107, 14781–14786 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Hauner, H. & Entenmann, G. Regional variation of adipose differentiation in cultured stromal-vascular cells from the abdominal and femoral adipose tissue of obese women. Int. J. Obes. 15, 121–126 (1991).

    CAS  PubMed  Google Scholar 

  35. Niesler, C. U., Siddle, K. & Prins, J. B. Human preadipocytes display a depot-specific susceptibility to apoptosis. Diabetes 47, 1365–1368 (1998).

    CAS  PubMed  Google Scholar 

  36. Tchkonia, T. et al. Fat depot origin affects adipogenesis in primary cultured and cloned human preadipocytes. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282, R1286–R1296 (2002).

    CAS  PubMed  Google Scholar 

  37. Van Harmelen, V., Rohrig, K. & Hauner, H. Comparison of proliferation and differentiation capacity of human adipocyte precursor cells from the omental and subcutaneous adipose tissue depot of obese subjects. Metabolism 53, 632–637 (2004).

    CAS  PubMed  Google Scholar 

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

    Google Scholar 

  39. 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 

  40. Tchkonia, T. et al. Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns. Am. J. Physiol. Endocrinol. Metab. 292, E298–E307 (2007).

    CAS  PubMed  Google Scholar 

  41. Sevastianova, K. et al. Comparison of dorsocervical with abdominal subcutaneous adipose tissue in patients with and without antiretroviral therapy-associated lipodystrophy. Diabetes 60, 1894–1900 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Lau, F. H. et al. Pattern specification and immune response transcriptional signatures of pericardial and subcutaneous adipose tissue. PLoS ONE 6, e26092 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 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 

  44. 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  PubMed Central  Google Scholar 

  45. Yamamoto, Y. et al. Adipose depots possess unique developmental gene signatures. Obesity (Silver Spring) 18, 872–878 (2010).

    CAS  Google Scholar 

  46. Walden, T. B., Hansen, I. R., Timmons, J. A., Cannon, B. & Nedergaard, J. Recruited vs. nonrecruited molecular signatures of brown, “brite,” and white adipose tissues. Am. J. Physiol. Endocrinol. Metab. 302, E19–E31 (2012).

    Article  CAS  PubMed  Google Scholar 

  47. Gesta, S. et al. Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration. Proc. Natl Acad. Sci. USA 108, 2771–2776 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Gburcik, V., Cawthorn, W. P., Nedergaard, J., Timmons, J. A. & Cannon, B. An essential role for Tbx15 in the differentiation of brown and “brite” but not white adipocytes. Am. J. Physiol. Endocrinol. Metab. 303, E1053–E1060 (2012).

    CAS  PubMed  Google Scholar 

  49. Divoux, A. et al. Identification of a novel lncRNA in gluteal adipose tissue and evidence for its positive effect on preadipocyte differentiation. Obesity (Silver Spring) 22, 1781–1785 (2014).

    CAS  Google Scholar 

  50. Chang, H. Y. Anatomic demarcation of cells: genes to patterns. Science 326, 1206–1207 (2009).

    CAS  PubMed  Google Scholar 

  51. Bradfield, J. P. et al. A genome-wide association meta-analysis identifies new childhood obesity loci. Nat. Genet. 44, 526–531 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Dankel, S. N. et al. Switch from stress response to homeobox transcription factors in adipose tissue after profound fat loss. PLoS ONE 5, e11033 (2010).

    PubMed  PubMed Central  Google Scholar 

  53. Cowherd, R. M., Lyle, R. E., Miller, C. P. & McGehee, R. E. Jr. Developmental profile of homeobox gene expression during 3T3-L1 adipogenesis. Biochem. Biophys. Res. Commun. 237, 470–475 (1997).

    CAS  PubMed  Google Scholar 

  54. Schleinitz, D. et al. Fat depot-specific mRNA expression of novel loci associated with waist–hip ratio. Int. J. Obes. (Lond.) 38, 120–125 (2014).

    CAS  Google Scholar 

  55. Basson, C. T. et al. Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome. Nat. Genet. 15, 30–35 (1997).

    CAS  PubMed  Google Scholar 

  56. Macotela, Y. et al. Intrinsic differences in adipocyte precursor cells from different white fat depots. Diabetes 61, 1691–1699 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Tchkonia, T. et al. Fat depot-specific characteristics are retained in strains derived from single human preadipocytes. Diabetes 55, 2571–2578 (2006).

    CAS  PubMed  Google Scholar 

  58. 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 

  59. Cao, H. et al. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 134, 933–944 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Dick, K. J. et al. DNA methylation and body-mass index: a genome-wide analysis. Lancet 383, 1990–1998 (2014).

    CAS  PubMed  Google Scholar 

  61. Gehrke, S. et al. Epigenetic regulation of depot-specific gene expression in adipose tissue. PLoS ONE 8, e82516 (2013).

    PubMed  PubMed Central  Google Scholar 

  62. Soshnikova, N. & Duboule, D. Epigenetic regulation of vertebrate Hox genes: a dynamic equilibrium. Epigenetics 4, 537–540 (2009).

    CAS  PubMed  Google Scholar 

  63. Rinn, J. L. et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129, 1311–1323 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Hilton, C., Neville, M. J. & Karpe, F. MicroRNAs in adipose tissue: their role in adipogenesis and obesity. Int. J. Obes. (Lond.) 37, 325–332 (2013).

    CAS  Google Scholar 

  65. Rantalainen, M. et al. MicroRNA expression in abdominal and gluteal adipose tissue is associated with mRNA expression levels and partly genetically driven. PLoS ONE 6, e27338 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Martin, M. L. & Jensen, M. D. Effects of body fat distribution on regional lipolysis in obesity. J. Clin. Invest. 88, 609–613 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 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 

  68. 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 

  69. 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 

  70. Manolopoulos, K. N., Karpe, F. & Frayn, K. N. Marked resistance of femoral adipose tissue blood flow and lipolysis to adrenaline in vivo. Diabetologia 55, 3029–3037 (2012).

    CAS  PubMed  Google Scholar 

  71. Marin, P., Rebuffe-Scrive, M., Smith, U. & Bjorntorp, P. Glucose uptake in human adipose tissue. Metabolism 36, 1154–1160 (1987).

    CAS  PubMed  Google Scholar 

  72. Gjedsted, J. et al. Effects of a 3-day fast on regional lipid and glucose metabolism in human skeletal muscle and adipose tissue. Acta Physiol. (Oxf.) 191, 205–216 (2007).

    CAS  Google Scholar 

  73. McQuaid, S. E. et al. Development of an arterio–venous difference method to study the metabolic physiology of the femoral adipose tissue depot. Obesity (Silver Spring) 18, 1055–1058 (2010).

    Google Scholar 

  74. Guo, Z., Johnson, C. M. & Jensen, M. D. Regional lipolytic responses to isoproterenol in women. Am. J. Physiol. 273, E108–E112 (1997).

    CAS  PubMed  Google Scholar 

  75. Frayn, K. N., Coppack, S. W. & Humphreys, S. M. Subcutaneous adipose tissue metabolism studied by local catheterization. Int. J. Obes. Relat. Metab. Disord. 17 (Suppl. 3), S18–S21 (1993).

    PubMed  Google Scholar 

  76. Marinou, K. et al. Structural and functional properties of deep abdominal subcutaneous adipose tissue explain its association with insulin resistance and cardiovascular risk in men. Diabetes Care 37, 821–829 (2014).

    PubMed  Google Scholar 

  77. 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 

  78. Lafontan, M., Dang-Tran, L. & Berlan, M. α-adrenergic antilipolytic effect of adrenaline in human fat cells of the thigh: comparison with adrenaline responsiveness of different fat deposits. Eur. J. Clin. Invest. 9, 261–266 (1979).

    CAS  PubMed  Google Scholar 

  79. 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 

  80. Gravholt, C. H., Dall, R., Christiansen, J. S., Moller, N. & Schmitz, O. Preferential stimulation of abdominal subcutaneous lipolysis after prednisolone exposure in humans. Obes. Res. 10, 774–781 (2002).

    CAS  PubMed  Google Scholar 

  81. Djurhuus, C. B. et al. Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans. Am. J. Physiol. Endocrinol. Metab. 283, E172–E177 (2002).

    CAS  PubMed  Google Scholar 

  82. Djurhuus, C. B. et al. Additive effects of cortisol and growth hormone on regional and systemic lipolysis in humans. Am. J. Physiol. Endocrinol. Metab. 286, E488–E494 (2004).

    CAS  PubMed  Google Scholar 

  83. Stefan, N. et al. Inhibition of 11β-HSD1 with RO5093151 for non-alcoholic fatty liver disease: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2, 406–416 (2014).

    CAS  PubMed  Google Scholar 

  84. Albu, J. B. et al. Metabolic changes following a 1-year diet and exercise intervention in patients with type 2 diabetes. Diabetes 59, 627–633 (2010).

    CAS  PubMed  Google Scholar 

  85. Okura, T., Nakata, Y., Yamabuki, K. & Tanaka, K. Regional body composition changes exhibit opposing effects on coronary heart disease risk factors. Arterioscler. Thromb. Vasc. Biol. 24, 923–929 (2004).

    CAS  PubMed  Google Scholar 

  86. Berentzen, T. & Sorensen, T. I. Effects of intended weight loss on morbidity and mortality: possible explanations of controversial results. Nutr. Rev. 64, 502–507 (2006).

    PubMed  Google Scholar 

  87. Ahlborg, G., Felig, P., Hagenfeldt, L., Hendler, R. & Wahren, J. Substrate turnover during prolonged exercise in man. Splanchnic and leg metabolism of glucose, free fatty acids, and amino acids. J. Clin. Invest. 53, 1080–1090 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. 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 

  89. Moro, C. et al. Exercise-induced lipid mobilization in subcutaneous adipose tissue is mainly related to natriuretic peptides in overweight men. Am. J. Physiol. Endocrinol. Metab. 295, E505–E513 (2008).

    CAS  PubMed  Google Scholar 

  90. Thompson, D., Karpe, F., Lafontan, M. & Frayn, K. Physical activity and exercise in the regulation of human adipose tissue physiology. Physiol. Rev. 92, 157–191 (2012).

    CAS  PubMed  Google Scholar 

  91. Marin, P., Rebuffe-Scrive, M. & Bjorntorp, P. Uptake of triglyceride fatty acids in adipose tissue in vivo in man. Eur. J. Clin. Invest. 20, 158–165 (1990).

    CAS  PubMed  Google Scholar 

  92. 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 

  93. Bickerton, A. S. et al. Preferential uptake of dietary fatty acids in adipose tissue and muscle in the postprandial period. Diabetes 56, 168–176 (2007).

    CAS  PubMed  Google Scholar 

  94. Koutsari, C., Snozek, C. L. & Jensen, M. D. Plasma NEFA storage in adipose tissue in the postprandial state: sex-related and regional differences. Diabetologia 51, 2041–2048 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Koutsari, C., Ali, A. H., Mundi, M. S. & Jensen, M. D. Storage of circulating free fatty acid in adipose tissue of postabsorptive humans: quantitative measures and implications for body fat distribution. Diabetes 60, 2032–2040 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. 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 

  97. Strawford, A., Antelo, F., Christiansen, M. & Hellerstein, M. K. Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation in humans measured with 2H2O. Am. J. Physiol. Endocrinol. Metab. 286, E577–E588 (2004).

    CAS  PubMed  Google Scholar 

  98. Capeau, J. et al. Human lipodystrophies: genetic and acquired diseases of adipose tissue. Endocr. Dev. 19, 1–20 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Majithia, A. R. et al. Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes. Proc. Natl Acad. Sci. USA 111, 13127–13132 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Gerstein, H. C. et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 368, 1096–1105 (2006).

    CAS  PubMed  Google Scholar 

  101. Kelly, I. E., Han, T. S., Walsh, K. & Lean, M. E. Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes. Diabetes Care 22, 288–293 (1999).

    CAS  PubMed  Google Scholar 

  102. Miyazaki, Y. et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J. Clin. Endocrinol. Metab. 87, 2784–2791 (2002).

    CAS  PubMed  Google Scholar 

  103. Mori, Y. et al. Effect of troglitazone on body fat distribution in type 2 diabetic patients. Diabetes Care 22, 908–912 (1999).

    CAS  PubMed  Google Scholar 

  104. Hwang, Y. C. et al. Effects of rosiglitazone on body fat distribution and insulin sensitivity in Korean type 2 diabetes mellitus patients. Metabolism 57, 479–487 (2008).

    CAS  PubMed  Google Scholar 

  105. McLaughlin, T. M. et al. Pioglitazone increases the proportion of small cells in human abdominal subcutaneous adipose tissue. Obesity (Silver Spring) 18, 926–931 (2010).

    CAS  Google Scholar 

  106. Shadid, S. & Jensen, M. D. Effects of pioglitazone versus diet and exercise on metabolic health and fat distribution in upper body obesity. Diabetes Care 26, 3148–3152 (2003).

    CAS  PubMed  Google Scholar 

  107. Punthakee, Z. et al. Impact of rosiglitazone on body composition, hepatic fat, fatty acids, adipokines and glucose in persons with impaired fasting glucose or impaired glucose tolerance: a sub-study of the DREAM trial. Diabet. Med. 31, 1086–1092 (2014).

    CAS  PubMed  Google Scholar 

  108. Malisova, L. et al. Expression of inflammation-related genes in gluteal and abdominal subcutaneous adipose tissue during weight-reducing dietary intervention in obese women. Physiol. Res. 63, 73–82 (2014).

    CAS  PubMed  Google Scholar 

  109. Apovian, C. M. et al. Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects. Arterioscler. Thromb. Vasc. Biol. 28, 1654–1659 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Wentworth, J. M. et al. Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes 59, 1648–1656 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Klimcakova, E. et al. Worsening of obesity and metabolic status yields similar molecular adaptations in human subcutaneous and visceral adipose tissue: decreased metabolism and increased immune response. J. Clin. Endocrinol. Metab. 96, E73–E82 (2011).

    CAS  PubMed  Google Scholar 

  112. Sun, S., Ji, Y., Kersten, S. & Qi, L. Mechanisms of inflammatory responses in obese adipose tissue. Annu. Rev. Nutr. 32, 261–286 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Nielsen, N. B. et al. Interstitial concentrations of adipokines in subcutaneous abdominal and femoral adipose tissue. Regul. Pept. 155, 39–45 (2009).

    CAS  PubMed  Google Scholar 

  114. Cantile, M., Procino, A., D'Armiento, M., Cindolo, L. & Cillo, C. HOX gene network is involved in the transcriptional regulation of in vivo human adipogenesis. J. Cell. Physiol. 194, 225–236 (2003).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

F.K. and K.E.P. acknowledge funding support from The Wellcome Trust, The British Heart Foundation, Heart Research UK and The European Union (EU FP6 MolPAGE [LSHG/512,066] and EU FP7 LipidomicNet [#202,272]). F.K. and K.E.P. also wish to thank the NIHR Oxford Biomedical Research Centre for supporting the Oxford BioBank and clinical fellows K. Manolopoulos and S. McQuaid and research nurses J. Cheeseman and L. Dennis for excellent support in collecting and analysing human material for the research discussed in this Review as unpublished work.

Author information

Authors and Affiliations

  1. Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington, OX3 7LE, UK

    Fredrik Karpe & Katherine E. Pinnick

  2. NIHR Oxford Biomedical Research Centre, OUH Trust, Churchill Hospital, Headington, OX3 7LE, UK

    Fredrik Karpe

Authors
  1. Fredrik Karpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katherine E. Pinnick
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors researched data for the article, provided substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

Corresponding authors

Correspondence to Fredrik Karpe or Katherine E. Pinnick.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karpe, F., Pinnick, K. Biology of upper-body and lower-body adipose tissue—link to whole-body phenotypes. Nat Rev Endocrinol 11, 90–100 (2015). https://doi.org/10.1038/nrendo.2014.185

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2014.185

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing