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:

The role of adipose tissue in cardiovascular health and disease

Abstract

Accumulating knowledge on the biology and function of the adipose tissue has led to a major shift in our understanding of its role in health and disease. The adipose tissue is now recognized as a crucial regulator of cardiovascular health, mediated by the secretion of several bioactive products, including adipocytokines, microvesicles and gaseous messengers, with a wide range of endocrine and paracrine effects on the cardiovascular system. The adipose tissue function and secretome are tightly controlled by complex homeostatic mechanisms and local cell–cell interactions, which can become dysregulated in obesity. Systemic or local inflammation and insulin resistance lead to a shift in the adipose tissue secretome from anti-inflammatory and anti-atherogenic towards a pro-inflammatory and pro-atherogenic profile. Moreover, the interplay between the adipose tissue and the cardiovascular system is bidirectional, with vascular-derived and heart-derived signals directly affecting adipose tissue biology. In this Review, we summarize the current knowledge of the biology and regional variability of adipose tissue in humans, deciphering the complex molecular mechanisms controlling the crosstalk between the adipose tissue and the cardiovascular system, and their possible clinical translation. In addition, we highlight the latest developments in adipose tissue imaging for cardiovascular risk stratification and discuss how therapeutic targeting of the adipose tissue can improve prevention and treatment of cardiovascular disease.

Key points

  • The adipose tissue is a crucial regulator of cardiovascular health and exerts both protective and deleterious effects on the cardiovascular system.

  • The biological profile of the adipose tissue largely depends on its expansion, body distribution and quality and differences in local biology.

  • The adipose tissue can affect local cardiovascular biology through the secretion of adipocytokines with endocrine and/or paracrine effects.

  • Conversely, pro-inflammatory and oxidative stimuli in diseased vessels and/or myocardium can modify adipose tissue biology, suggesting a bidirectional interplay between the adipose tissue and the cardiovascular system.

  • Several traditional and experimental imaging modalities can be exploited to characterize both quantitative and qualitative adipose tissue features with important implications in cardiometabolic risk stratification.

  • The adipose tissue is a promising therapeutic target in cardiovascular therapeutics and might mediate the cardiovascular benefit observed with different pharmacological, lifestyle and other types of interventions.

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

Access options

Buy this article

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

Fig. 1: Effects of the adipose tissue in the cardiovascular system.
Fig. 2: Interplay between the adipose tissue and the vascular wall.
Fig. 3: Interplay between the adipose tissue and the myocardium.
Fig. 4: Noninvasive imaging for adipose tissue phenotyping.

Similar content being viewed by others

References

  1. Benjamin, E. J. et al. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation 135, e146–e603 (2017).

    PubMed  PubMed Central  Google Scholar 

  2. Rimm, E. B. et al. Body size and fat distribution as predictors of coronary heart disease among middle-aged and older US men. Am. J. Epidemiol. 141, 1117–1127 (1995).

    CAS  PubMed  Google Scholar 

  3. Hartz, A. J., Rupley, D. C. Jr., Kalkhoff, R. D. & Rimm, A. A. Relationship of obesity to diabetes: influence of obesity level and body fat distribution. Prev. Med. 12, 351–357 (1983).

    CAS  PubMed  Google Scholar 

  4. Aune, D. et al. BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants. BMJ 353, i2156 (2016).

    PubMed  PubMed Central  Google Scholar 

  5. Powell-Wiley, T. M. et al. Impact of body mass index on heart failure by race/ethnicity from get with the guidelines-heart failure (GWTG-HF) registry. JACC Heart Fail 6, 233–242 (2018).

    PubMed  PubMed Central  Google Scholar 

  6. Britton, K. A. et al. Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality. J. Am. Coll. Cardiol. 62, 921–925 (2013).

    PubMed  PubMed Central  Google Scholar 

  7. Silva, K. R. et al. Characterization of stromal vascular fraction and adipose stem cells from subcutaneous, preperitoneal and visceral morbidly obese human adipose tissue depots. PLOS ONE 12, e0174115 (2017).

    PubMed  PubMed Central  Google Scholar 

  8. 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 

  9. 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 

  10. Flier, J. S., Cook, K. S., Usher, P. & Spiegelman, B. M. Severely impaired adipsin expression in genetic and acquired obesity. Science 237, 405–408 (1987).

    CAS  PubMed  Google Scholar 

  11. Akoumianakis, I. & Antoniades, C. The interplay between adipose tissue and the cardiovascular system: is fat always bad? Cardiovasc. Res. 113, 999–1008 (2017).

    CAS  PubMed  Google Scholar 

  12. Wajchenberg, B. L. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr. Rev. 21, 697–738 (2000).

    CAS  PubMed  Google Scholar 

  13. Iacobellis, G. Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat. Rev. Endocrinol. 11, 363–371 (2015).

    CAS  PubMed  Google Scholar 

  14. 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 

  15. Salgado-Somoza, A., Teijeira-Fernandez, E., Fernandez, A. L., Gonzalez-Juanatey, J. R. & Eiras, S. Proteomic analysis of epicardial and subcutaneous adipose tissue reveals differences in proteins involved in oxidative stress. Am. J. Physiol. Heart Circ. Physiol. 299, H202–H209 (2010).

    CAS  PubMed  Google Scholar 

  16. Passaro, A. et al. Gene expression regional differences in human subcutaneous adipose tissue. BMC Genomics 18, 202 (2017).

    PubMed  PubMed Central  Google Scholar 

  17. Gaborit, B. et al. Human epicardial adipose tissue has a specific transcriptomic signature depending on its anatomical peri-atrial, peri-ventricular, or peri-coronary location. Cardiovasc. Res. 108, 62–73 (2015).

    CAS  PubMed  Google Scholar 

  18. Leitner, B. P. et al. Mapping of human brown adipose tissue in lean and obese young men. Proc. Natl Acad. Sci. USA 114, 8649–8654 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Harms, M. & Seale, P. Brown and beige fat: development, function and therapeutic potential. Nat. Med. 19, 1252–1263 (2013).

    CAS  PubMed  Google Scholar 

  20. Villarroya, F., Cereijo, R., Villarroya, J. & Giralt, M. Brown adipose tissue as a secretory organ. Nat. Rev. Endocrinol. 13, 26–35 (2017).

    CAS  PubMed  Google Scholar 

  21. Stanford, K. I. et al. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J. Clin. Invest. 123, 215–223 (2013).

    CAS  PubMed  Google Scholar 

  22. Gronthos, S. et al. Surface protein characterization of human adipose tissue-derived stromal cells. J. Cell. Physiol. 189, 54–63 (2001).

    CAS  PubMed  Google Scholar 

  23. Antonopoulos, A. S. et al. Reciprocal effects of systemic inflammation and brain natriuretic peptide on adiponectin biosynthesis in adipose tissue of patients with ischemic heart disease. Arterioscler Thromb. Vasc. Biol. 34, 2151–2159 (2014).

    CAS  PubMed  Google Scholar 

  24. Srikakulapu, P. et al. Perivascular adipose tissue harbors atheroprotective IgM-producing B cells. Front. Physiol. 8, 719 (2017).

    PubMed  PubMed Central  Google Scholar 

  25. Withers, S. B. et al. Eosinophils are key regulators of perivascular adipose tissue and vascular functionality. Sci. Rep. 7, 44571 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Zuk, P. A. et al. Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell 13, 4279–4295 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Tilg, H. & Moschen, A. R. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat. Rev. Immunol. 6, 772–783 (2006).

    CAS  PubMed  Google Scholar 

  28. Chusyd, D. E., Wang, D., Huffman, D. M. & Nagy, T. R. Relationships between rodent white adipose fat pads and human white adipose fat depots. Front. Nutr. 3, 10 (2016).

    PubMed  PubMed Central  Google Scholar 

  29. 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 

  30. Krotkiewski, M., Bjorntorp, P., Sjostrom, L. & Smith, U. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J. Clin. Invest. 72, 1150–1162 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Salans, L. B., Knittle, J. L. & Hirsch, J. The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity. J. Clin. Invest. 47, 153–165 (1968).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Rutkowski, J. M., Stern, J. H. & Scherer, P. E. The cell biology of fat expansion. J. Cell Biol. 208, 501–512 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Kursawe, R. et al. Cellularity and adipogenic profile of the abdominal subcutaneous adipose tissue from obese adolescents: association with insulin resistance and hepatic steatosis. Diabetes 59, 2288–2296 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Guzik, T. J., Skiba, D. S., Touyz, R. M. & Harrison, D. G. The role of infiltrating immune cells in dysfunctional adipose tissue. Cardiovasc. Res. 113, 1009–1023 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Weisberg, S. P. et al. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796–1808 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Cildir, G., Akincilar, S. C. & Tergaonkar, V. Chronic adipose tissue inflammation: all immune cells on the stage. Trends Mol. Med. 19, 487–500 (2013).

    CAS  PubMed  Google Scholar 

  37. Caer, C. et al. Immune cell-derived cytokines contribute to obesity-related inflammation, fibrogenesis and metabolic deregulation in human adipose tissue. Sci. Rep. 7, 3000 (2017).

    PubMed  PubMed Central  Google Scholar 

  38. Lumeng, C. N., Bodzin, J. L. & Saltiel, A. R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117, 175–184 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Fujisaka, S. et al. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58, 2574–2582 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Onogi, Y. et al. PDGFRbeta regulates adipose tissue expansion and glucose metabolism via vascular remodeling in diet-induced obesity. Diabetes 66, 1008–1021 (2017).

    CAS  PubMed  Google Scholar 

  41. Pasarica, M. et al. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 58, 718–725 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Chadderdon, S. M. et al. Proinflammatory endothelial activation detected by molecular imaging in obese nonhuman primates coincides with onset of insulin resistance and progressively increases with duration of insulin resistance. Circulation 129, 471–478 (2014).

    CAS  PubMed  Google Scholar 

  43. Halberg, N. et al. Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Mol. Cell. Biol. 29, 4467–4483 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Escobedo, N. et al. Restoration of lymphatic function rescues obesity in Prox1-haploinsufficient mice. JCI Insight 1, e85096 (2016).

    PubMed  PubMed Central  Google Scholar 

  45. Li, G. et al. Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota. Cell Metab. 26, 672–685 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Franssens, B. T., Hoogduin, H., Leiner, T., van der Graaf, Y. & Visseren, F. L. J. Relation between brown adipose tissue and measures of obesity and metabolic dysfunction in patients with cardiovascular disease. J. Magn. Reson. Imag. 46, 497–504 (2017).

    Google Scholar 

  47. Chechi, K. et al. Functional characterization of the Ucp1-associated oxidative phenotype of human epicardial adipose tissue. Sci. Rep. 7, 15566 (2017).

    PubMed  PubMed Central  Google Scholar 

  48. Oikonomou, E. K. & Antoniades, C. Immunometabolic regulation of vascular redox state: the role of adipose tissue. Antioxid. Redox Signal 29, 313–336 (2017).

    PubMed  Google Scholar 

  49. Sun, Q. et al. Plasma retinol-binding protein 4 (RBP4) levels and risk of coronary heart disease a prospective analysis among women in the Nurses’ Health Study. Circulation 127, 1938–1947 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Jacques, C. et al. Proinflammatory actions of visfatin/nicotinamide phosphoribosyltransferase (Nampt) involve regulation of insulin signaling pathway and nampt enzymatic activity. J. Biol. Chem. 287, 15100–15108 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Weng, C. et al. Effects of chemerin/CMKLR1 in obesity-induced hypertension and potential mechanism. Am. J. Transl Res. 9, 3096–3104 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Feng, R. et al. Higher vaspin levels in subjects with obesity and type 2 diabetes mellitus: a meta-analysis. Diabetes Res. Clin. Pract. 106, 88–94 (2014).

    CAS  PubMed  Google Scholar 

  53. Fontana, A. et al. Association between resistin levels and all-cause and cardiovascular mortality: a new study and a systematic review and meta-analysis. PLOS ONE 10, e0120419 (2015).

    PubMed  PubMed Central  Google Scholar 

  54. Narumi, T. et al. Impact of serum omentin-1 levels on cardiac prognosis in patients with heart failure. Eur. Heart J. 35, 221–222 (2014).

    Google Scholar 

  55. Wu, Z. J., Cheng, Y. J., Gu, W. J. & Aung, L. H. Adiponectin is associated with increased mortality in patients with already established cardiovascular disease: a systematic review and meta-analysis. Metabolism 63, 1157–1166 (2014).

    CAS  PubMed  Google Scholar 

  56. Margaritis, M. et al. Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels. Circulation 127, 2209–2221 (2013).

    CAS  PubMed  Google Scholar 

  57. Taube, A., Schlich, R., Sell, H., Eckardt, K. & Eckel, J. Inflammation and metabolic dysfunction: links to cardiovascular diseases. Am. J. Physiol. Heart Circ. Physiol. 302, H2148–H2165 (2012).

    CAS  PubMed  Google Scholar 

  58. Antonopoulos, A. S., Oikonomou, E. K., Antoniades, C. & Tousoulis, D. From the BMI paradox to the obesity paradox: the obesity-mortality association in coronary heart disease. Obes. Rev. 17, 989–1000 (2016).

    CAS  PubMed  Google Scholar 

  59. Uretsky, S. et al. Obesity paradox in patients with hypertension and coronary artery disease. Am. J. Med. 120, 863–870 (2007).

    PubMed  Google Scholar 

  60. Khawaja, T. et al. Epicardial fat volume in patients with left ventricular systolic dysfunction. Am. J. Cardiol. 108, 397–401 (2011).

    PubMed  Google Scholar 

  61. Lavie, C. J. et al. Impact of cardiorespiratory fitness on the obesity paradox in patients with heart failure. Mayo Clin. Proc. 88, 251–258 (2013).

    PubMed  Google Scholar 

  62. Lavie, C. J., Osman, A. F., Milani, R. V. & Mehra, M. R. Body composition and prognosis in chronic systolic heart failure: the obesity paradox. Am. J. Cardiol. 91, 891–894 (2003).

    PubMed  Google Scholar 

  63. Hall, J. E., do Carmo, J. M., da Silva, A. A., Wang, Z. & Hall, M. E. Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms. Circ. Res. 116, 991–1006 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Asferg, C. L. et al. Relative atrial natriuretic peptide deficiency and inadequate renin and angiotensin II suppression in obese hypertensive men. Hypertension 62, 147–153 (2013).

    CAS  PubMed  Google Scholar 

  65. Vilahur, G., Ben-Aicha, S. & Badimon, L. New insights into the role of adipose tissue in thrombosis. Cardiovasc. Res. 113, 1046–1054 (2017).

    CAS  PubMed  Google Scholar 

  66. Thomou, T. et al. Adipose-derived circulating mi-RNAs regulate gene expression in other tissues. Nature 542, 450–455 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Xie, Z. et al. Adipose-derived exosomes exert proatherogenic effects by regulating macrophage foam cell formation and polarization. J. Am. Heart Assoc. 7, e007442 (2018).

    PubMed  PubMed Central  Google Scholar 

  68. King, A. L. et al. Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent. Proc. Natl Acad. Sci. USA 111, 3182–3187 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Lee, Y. C. et al. Role of perivascular adipose tissue-derived methyl palmitate in vascular tone regulation and pathogenesis of hypertension. Circulation 124, 1160–1171 (2011).

    PubMed  Google Scholar 

  70. Akoumianakis, I., Tarun, A. & Antoniades, C. Perivascular adipose tissue as a regulator of vascular disease pathogenesis: identifying novel therapeutic targets. Br. J. Pharmacol. 174, 3411–3424 (2017).

    CAS  PubMed  Google Scholar 

  71. Yudkin, J. S., Eringa, E. & Stehouwer, C. D. “Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet 365, 1817–1820 (2005).

    PubMed  Google Scholar 

  72. Chen, H., Montagnani, M., Funahashi, T., Shimomura, I. & Quon, M. J. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J. Biol. Chem. 278, 45021–45026 (2003).

    CAS  PubMed  Google Scholar 

  73. Antonopoulos, A. S. et al. Adiponectin as a link between type 2 diabetes and vascular NADPH oxidase activity in the human arterial wall: the regulatory role of perivascular adipose tissue. Diabetes 64, 2207–2219 (2015).

    CAS  PubMed  Google Scholar 

  74. Chang, L. et al. Bmal1 in perivascular adipose tissue regulates resting phase blood pressure through transcriptional regulation of angiotensinogen. Circulation 138, 67–79 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Ayala-Lopez, N., Thompson, J. M. & Watts, S. W. Perivascular adipose tissue’s impact on norepinephrine-induced contraction of mesenteric resistance arteries. Front. Physiol. 8, 37 (2017).

    PubMed  PubMed Central  Google Scholar 

  76. Friederich-Persson, M., Nguyen Dinh Cat, A., Persson, P., Montezano, A. C. & Touyz, R. M. Brown adipose tissue regulates small artery function through NADPH oxidase 4-derived hydrogen peroxide and redox-sensitive protein kinase G-1alpha. Arterioscler Thromb. Vasc. Biol. 37, 455–465 (2017).

    CAS  PubMed  Google Scholar 

  77. Margaritis, M. et al. Predictive value of telomere length on outcome following acute myocardial infarction: evidence for contrasting effects of vascular versus blood oxidative stress. Eur. Heart J. 38, 3094–3104 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Antoniades, C. et al. Preoperative atorvastatin treatment in CABG patients rapidly improves vein graft redox state by inhibition of Rac1 and NADPH-oxidase activity. Circulation 122, S66–73 (2010).

    CAS  PubMed  Google Scholar 

  79. Langbein, H. et al. NADPH oxidase 4 protects against development of endothelial dysfunction and atherosclerosis in LDL receptor deficient mice. Eur. Heart J. 37, 1753–1761 (2016).

    CAS  PubMed  Google Scholar 

  80. Antoniades, C. et al. 5-Methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation 114, 1193–1201 (2006).

    CAS  PubMed  Google Scholar 

  81. Han, F. et al. C1q/TNF-related protein 9 improves the anti-contractile effects of perivascular adipose tissue via the AMPK-eNOS pathway in diet-induced obese mice. Clin. Exp. Pharmacol. Physiol. 45, 50–57 (2018).

    CAS  PubMed  Google Scholar 

  82. Sena, C. M., Pereira, A., Fernandes, R., Letra, L. & Seica, R. M. Adiponectin improves endothelial function in mesenteric arteries of rats fed a high-fat diet: role of perivascular adipose tissue. Br. J. Pharmacol. 174, 3514–3526 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Neves, K. B. et al. Chemerin reduces vascular nitric oxide/cGMP signalling in rat aorta: a link to vascular dysfunction in obesity? Clin. Sci. 127, 111–122 (2014).

    CAS  Google Scholar 

  84. Lee, W. J. et al. Visfatin-induced expression of inflammatory mediators in human endothelial cells through the NF-κB pathway. Int. J. Obes. 33, 465–472 (2009).

    CAS  Google Scholar 

  85. Sweeney, G. Cardiovascular effects of leptin. Nat. Rev. Cardiol. 7, 22–29 (2010).

    CAS  PubMed  Google Scholar 

  86. Hubert, A. et al. Selective deletion of leptin signaling in endothelial cells enhances neointima formation and phenocopies the vascular effects of diet-induced obesity in mice. Arterioscler Thromb. Vasc. Biol. 37, 1683–1697 (2017).

    CAS  PubMed  Google Scholar 

  87. Deiuliis, J. A. et al. Visceral adipose microRNA 223 is upregulated in human and murine obesity and modulates the inflammatory phenotype of macrophages. PLOS ONE 11, e0165962 (2016).

    PubMed  PubMed Central  Google Scholar 

  88. Mari-Alexandre, J. et al. Thickness and an altered miRNA expression in the epicardial adipose tissue is associated with coronary heart disease in sudden death victims. Rev. Esp. Cardiol. https://doi.org/10.1016/j.rec.2017.12.007 (2018).

    Article  Google Scholar 

  89. Renovato-Martins, M. et al. Microparticles derived from obese adipose tissue elicit a pro-inflammatory phenotype of CD16+, CCR5+ and TLR8+ monocytes. Biochim. Biophys. Acta 1863, 139–151 (2017).

    CAS  Google Scholar 

  90. Ying, W. et al. Adipose tissue macrophage-derived exosomal mi-RNAs can modulate in vivo and in vitro insulin sensitivity. Cell 171, 372–384 (2017).

    CAS  PubMed  Google Scholar 

  91. Fischer, C. et al. A miR-327-FGF10-FGFR2-mediated autocrine signaling mechanism controls white fat browning. Nat. Commun. 8, 2079 (2017).

    PubMed  PubMed Central  Google Scholar 

  92. Icli, B. & Feinberg, M. W. MicroRNAs in dysfunctional adipose tissue: cardiovascular implications. Cardiovasc. Res. 113, 1024–1034 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Kristensen, M. M. et al. mi-RNAs in human subcutaneous adipose tissue: effects of weight loss induced by hypocaloric diet and exercise. Obesity 25, 572–580 (2017).

    CAS  Google Scholar 

  94. Candela, J., Wang, R. & White, C. Microvascular endothelial dysfunction in obesity is driven by macrophage-dependent hydrogen sulfide depletion. Arterioscler Thromb. Vasc. Biol. 37, 889–899 (2017).

    CAS  PubMed  Google Scholar 

  95. Xia, N. et al. Uncoupling of endothelial nitric oxide synthase in perivascular adipose tissue of diet-induced obese mice. Arterioscler Thromb. Vasc. Biol. 36, 78–85 (2016).

    CAS  PubMed  Google Scholar 

  96. Mikolajczyk, T. P. et al. Role of chemokine RANTES in the regulation of perivascular inflammation, T cell accumulation, and vascular dysfunction in hypertension. FASEB J. 30, 1987–1999 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Ruan, C. C. et al. Complement-mediated inhibition of adiponectin regulates perivascular inflammation and vascular injury in hypertension. FASEB J. 31, 1120–1129 (2017).

    CAS  PubMed  Google Scholar 

  98. Abu Bakar, H., Robert Dunn, W., Daly, C. & Ralevic, V. Sensory innervation of perivascular adipose tissue: a crucial role in artery vasodilatation and leptin release. Cardiovasc. Res. 113, 962–972 (2017).

    PubMed  Google Scholar 

  99. Antonopoulos, A. S. & Antoniades, C. The role of epicardial adipose tissue in cardiac biology: classic concepts and emerging roles. J. Physiol. 595, 3907–3917 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Antonopoulos, A. S. et al. Mutual regulation of epicardial adipose tissue and myocardial redox state by PPAR-gamma/adiponectin signalling. Circ. Res. 118, 842–855 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Antoniades, C. et al. Myocardial redox state predicts in-hospital clinical outcome after cardiac surgery effects of short-term pre-operative statin treatment. J. Am. Coll. Cardiol. 59, 60–70 (2012).

    CAS  PubMed  Google Scholar 

  102. Grunberg, J. R. et al. Overexpressing the novel autocrine/endocrine adipokine WISP2 induces hyperplasia of the heart, white and brown adipose tissues and prevents insulin resistance. Sci. Rep. 7, 43515 (2017).

    PubMed  PubMed Central  Google Scholar 

  103. Gao, W. et al. Retinol-binding protein 4 induces cardiomyocyte hypertrophy by activating TLR4/MyD88 pathway. Endocrinology 157, 2282–2293 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Blumensatt, M. et al. Activin A impairs insulin action in cardiomyocytes via up-regulation of miR-143. Cardiovasc. Res. 100, 201–210 (2013).

    CAS  PubMed  Google Scholar 

  105. Rodriguez-Penas, D. et al. The adipokine chemerin induces apoptosis in cardiomyocytes. Cell Physiol. Biochem. 37, 176–192 (2015).

    CAS  PubMed  Google Scholar 

  106. Blumensatt, M. et al. Secretory products from epicardial adipose tissue from patients with type 2 diabetes impair mitochondrial beta-oxidation in cardiomyocytes via activation of the cardiac renin-angiotensin system and induction of miR-208a. Bas. Res. Cardiol. 112, 2 (2017).

    Google Scholar 

  107. Sawaki, D. et al. Visceral adipose tissue drives cardiac aging through modulation of fibroblast senescence by osteopontin production. Circulation 138, 809–822 (2018).

    CAS  PubMed  Google Scholar 

  108. Gutierrez-Tenorio, J. et al. The role of oxidative stress in the crosstalk between leptin and mineralocorticoid receptor in the cardiac fibrosis associated with obesity. Sci. Rep. 7, 16802 (2017).

    PubMed  PubMed Central  Google Scholar 

  109. Wang, Q. et al. The crucial role of activin A/ALK4 pathway in the pathogenesis of Ang-II-induced atrial fibrosis and vulnerability to atrial fibrillation. Bas. Res. Cardiol. 112, 47 (2017).

    CAS  Google Scholar 

  110. Venteclef, N. et al. Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines. Eur. Heart J. 36, 795–805a (2015).

    CAS  PubMed  Google Scholar 

  111. Bernasochi, G. B. et al. Pericardial adipose and aromatase: a new translational target for aging, obesity and arrhythmogenesis? J. Mol. Cell Cardiol. 111, 96–101 (2017).

    CAS  PubMed  Google Scholar 

  112. Haemers, P. et al. Atrial fibrillation is associated with the fibrotic remodelling of adipose tissue in the subepicardium of human and sheep atria. Eur. Heart J. 38, 53–61 (2017).

    CAS  PubMed  Google Scholar 

  113. Jiang, D. S. et al. Aberrant epicardial adipose tissue extracellular matrix remodeling in patients with severe ischemic cardiomyopathy: insight from comparative quantitative proteomics. Sci. Rep. 7, 43787 (2017).

    PubMed  PubMed Central  Google Scholar 

  114. Salatzki, J. et al. Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced left ventricular failure. PLOS Genet. 14, e1007171 (2018).

    PubMed  PubMed Central  Google Scholar 

  115. Perez-Belmonte, L. M. et al. Expression of epicardial adipose tissue thermogenic genes in patients with reduced and preserved ejection fraction heart failure. Int. J. Med. Sci. 14, 891–895 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Takaoka, M. et al. Endovascular injury induces rapid phenotypic changes in perivascular adipose tissue. Arterioscler Thromb. Vasc. Biol. 30, 1576–1582 (2010).

    CAS  PubMed  Google Scholar 

  117. Cybularz, M. et al. Endothelial function and gene expression in perivascular adipose tissue from internal mammary arteries of obese patients with coronary artery disease. Atheroscler Suppl. 30, 149–158 (2017).

    PubMed  Google Scholar 

  118. Antonopoulos, A. S. et al. Detecting human coronary inflammation by imaging perivascular fat. Sci. Transl Med. 9, eaal2658 (2017).

    PubMed  Google Scholar 

  119. Liu, D., Ceddia, R. P. & Collins, S. Cardiac natriuretic peptides promote adipose ‘browning’ through mTOR complex-1. Mol. Metab. 9, 192–198 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Wu, W. et al. Enhancing natriuretic peptide signaling in adipose tissue, but not in muscle, protects against diet-induced obesity and insulin resistance. Sci. Signal. 10, eaam6870 (2017).

    PubMed  PubMed Central  Google Scholar 

  121. Suffee, N. et al. Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria. Proc. Natl Acad. Sci. USA 114, E771–E780 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Di Costanzo, A. et al. Non-alcoholic fatty liver disease and subclinical atherosclerosis: a comparison of metabolically- versus genetically-driven excess fat hepatic storage. Atherosclerosis 257, 232–239 (2017).

    PubMed  Google Scholar 

  123. Targher, G., Byrne, C. D., Lonardo, A., Zoppini, G. & Barbui, C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J. Hepatol. 65, 589–600 (2016).

    PubMed  Google Scholar 

  124. Levelt, E. et al. Ectopic and visceral fat deposition in lean and obese patients with type 2 diabetes. J. Am. Coll. Cardiol. 68, 53–63 (2016).

    PubMed  PubMed Central  Google Scholar 

  125. Fabbrini, E. et al. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc. Natl Acad. Sci. USA 106, 15430–15435 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Adolph, T. E., Grander, C., Grabherr, F. & Tilg, H. Adipokines and non-alcoholic fatty liver disease: multiple interactions. Int. J. Mol. Sci. 18, E1649 (2017).

    PubMed  Google Scholar 

  127. Terry, J. G. et al. Intermuscular adipose tissue and subclinical coronary artery calcification in midlife: the CARDIA Study (Coronary Artery Risk Development in Young Adults). Arterioscler Thromb. Vasc. Biol. 37, 2370–2378 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Dale, C. E. et al. Causal associations of adiposity and body fat distribution with coronary heart disease, stroke subtypes, and type 2 diabetes mellitus: a mendelian randomization analysis. Circulation 135, 2373–2388 (2017).

    PubMed  PubMed Central  Google Scholar 

  129. Chandra, A. et al. The relationship of body mass and fat distribution with incident hypertension: observations from the Dallas Heart Study. J. Am. Coll. Cardiol. 64, 997–1002 (2014).

    PubMed  Google Scholar 

  130. Neeland, I. J. et al. Body fat distribution and incident cardiovascular disease in obese adults. J. Am. Coll. Cardiol. 65, 2150–2151 (2015).

    PubMed  PubMed Central  Google Scholar 

  131. Mancio, J. et al. Epicardial adipose tissue volume assessed by computed tomography and coronary artery disease: a systematic review and meta-analysis. Eur. Heart J. Cardiovasc. Imag. 19, 490–497 (2017).

    Google Scholar 

  132. Heckbert, S. R. et al. Pericardial fat volume and incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis and Jackson Heart Study. Obesity 25, 1115–1121 (2017).

    CAS  Google Scholar 

  133. Lazaros, G. et al. Prognostic implications of epicardial fat volume quantification in acute pericarditis. Eur. J. Clin. Invest. 47, 129–136 (2017).

    CAS  PubMed  Google Scholar 

  134. Takx, R. A. et al. Supraclavicular brown adipose tissue 18F-FDG uptake and cardiovascular disease. J. Nucl. Med. 57, 1221–1225 (2016).

    CAS  PubMed  Google Scholar 

  135. Hung, W. C. et al. Plasma visfatin levels are associated with major adverse cardiovascular events in patients with acute ST-elevation myocardial infarction. Clin. Invest. Med. 38, E100–E109 (2015).

    CAS  PubMed  Google Scholar 

  136. Lemieux, I. et al. Hypertriglyceridemic waist: a marker of the atherogenic metabolic triad (hyperinsulinemia; hyperapolipoprotein B; small, dense LDL) in men? Circulation 102, 179–184 (2000).

    CAS  PubMed  Google Scholar 

  137. Kaul, S. et al. Dual-energy X-ray absorptiometry for quantification of visceral fat. Obesity 20, 1313–1318 (2012).

    Google Scholar 

  138. Iacobellis, G. et al. Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: a new indicator of cardiovascular risk. J. Clin. Endocrinol. Metab. 88, 5163–5168 (2003).

    CAS  PubMed  Google Scholar 

  139. Davidovich, D., Gastaldelli, A. & Sicari, R. Imaging cardiac fat. Eur. Heart J. Cardiovasc. Imag. 14, 625–630 (2013).

    Google Scholar 

  140. Verma, S. K. et al. Differentiating brown and white adipose tissues by high-resolution diffusion NMR spectroscopy. J. Lipid Res. 58, 289–298 (2017).

    CAS  PubMed  Google Scholar 

  141. Mazurek, T. et al. PET/CT evaluation of (18)F-FDG uptake in pericoronary adipose tissue in patients with stable coronary artery disease: independent predictor of atherosclerotic lesions’ formation? J. Nucl. Cardiol. 24, 1075–1084 (2017).

    PubMed  Google Scholar 

  142. Ohyama, K. et al. Association of coronary perivascular adipose tissue inflammation and drug-eluting stent-induced coronary hyperconstricting responses in pigs: 18F-fluorodeoxyglucose positron emission tomography imaging study. Arterioscler Thromb. Vasc. Biol. 37, 1757–1764 (2017).

    CAS  PubMed  Google Scholar 

  143. Ohyama, K. et al. Coronary adventitial and perivascular adipose tissue inflammation in patients with vasospastic angina. J. Am. Coll. Cardiol. 71, 414–425 (2018).

    PubMed  Google Scholar 

  144. Cote, J. A. et al. Computed tomography-measured adipose tissue attenuation and area both predict adipocyte size and cardiometabolic risk in women. Adipocyte 5, 35–42 (2016).

    CAS  PubMed  Google Scholar 

  145. Ganesan, G. et al. Diffuse optical spectroscopic imaging of subcutaneous adipose tissue metabolic changes during weight loss. Int. J. Obes. 40, 1292–1300 (2016).

    CAS  Google Scholar 

  146. Dinish, U. S. et al. Diffuse optical spectroscopy and imaging to detect and quantify adipose tissue browning. Sci. Rep. 7, 41357 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Branca, R. T. et al. Accurate quantification of brown adipose tissue mass by xenon-enhanced computed tomography. Proc. Natl Acad. Sci. USA 115, 174–179 (2018).

    CAS  PubMed  Google Scholar 

  148. Farb, M. G., Park, S. Y., Karki, S. & Gokce, N. Assessment of human adipose tissue microvascular function using videomicroscopy. J. Vis. Exp. https://doi.org/10.3791/56079 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  149. ORIGIN Trials Investigators et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N. Engl. J. Med. 367, 319–328 (2012).

    Google Scholar 

  150. Marso, S. P. et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375, 311–322 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Green, J. B. et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 373, 232–242 (2015).

    CAS  PubMed  Google Scholar 

  152. Zinman, B. et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N. Engl. J. Med. 373, 2117–2128 (2015).

    CAS  PubMed  Google Scholar 

  153. Iacobellis, G., Mohseni, M., Bianco, S. D. & Banga, P. K. Liraglutide causes large and rapid epicardial fat reduction. Obesity 25, 311–316 (2017).

    CAS  Google Scholar 

  154. Lamers, D. et al. Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes 60, 1917–1925 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Zhuge, F. et al. DPP-4 inhibition by linagliptin attenuates obesity-related inflammation and insulin resistance by regulating M1/M2 macrophage polarization. Diabetes 65, 2966–2979 (2016).

    CAS  PubMed  Google Scholar 

  156. Marques, A. P. et al. Dipeptidyl peptidase IV (DPP-IV) inhibition prevents fibrosis in adipose tissue of obese mice. Biochim. Biophys. Acta 1862, 403–413 (2018).

    CAS  Google Scholar 

  157. Kosi-Trebotic, L. et al. Gliptin therapy reduces hepatic and myocardial fat in type 2 diabetic patients. Eur. J. Clin. Invest. 47, 829–838 (2017).

    CAS  PubMed  Google Scholar 

  158. Kim Chung le, T. et al. Exendin-4, a GLP-1 receptor agonist, directly induces adiponectin expression through protein kinase A pathway and prevents inflammatory adipokine expression. Biochem. Biophys. Res. Commun. 390, 613–618 (2009).

    PubMed  Google Scholar 

  159. Xu, F. et al. GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1. Diabetologia 59, 1059–1069 (2016).

    CAS  PubMed  Google Scholar 

  160. Diaz-Rodriguez, E. et al. Effects of dapagliflozin on human epicardial adipose tissue: modulation of insulin resistance, inflammatory chemokine production, and differentiation ability. Cardiovasc. Res. 114, 336–346 (2018).

    CAS  PubMed  Google Scholar 

  161. Sato, T. et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc. Diabetol 17, 6 (2018).

    PubMed  PubMed Central  Google Scholar 

  162. Neeland, I. J. et al. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA 308, 1150–1159 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Nissen, S. E. & Wolski, K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N. Engl. J. Med. 356, 2457–2471 (2007).

    CAS  PubMed  Google Scholar 

  164. Quesada, I. et al. Vascular dysfunction elicited by a cross talk between periaortic adipose tissue and the vascular wall is reversed by pioglitazone. Cardiovasc. Ther. 36, e12322 (2018).

    PubMed  Google Scholar 

  165. Kumar, D. et al. Saroglitazar reduces obesity and associated inflammatory consequences in murine adipose tissue. Eur. J. Pharmacol. 822, 32–42 (2018).

    CAS  PubMed  Google Scholar 

  166. Adams, M. et al. Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation. J. Clin. Invest. 100, 3149–3153 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Than, A. et al. Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis. Signal Transduct. Target. Ther. 2, 17022 (2017).

    PubMed  PubMed Central  Google Scholar 

  168. Sakaue, T. et al. Perivascular adipose tissue angiotensin II type 1 receptor promotes vascular inflammation and aneurysm formation. Hypertension 70, 780–789 (2017).

    CAS  PubMed  Google Scholar 

  169. Jia, G. H. H., Aroor, A. R. & Sowers, J. R. The role of mineralocorticoid receptor signaling in the cross-talk between adipose tissue and the vascular wall. Cardiovasc. Res. 113, 1055–1063 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Skiba, D. S. et al. Anti-atherosclerotic effect of the angiotensin 1–7 mimetic AVE0991 is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis. Br. J. Pharmacol. 174, 4055–4069 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Hoeke, G. et al. Atorvastatin accelerates clearance of lipoprotein remnants generated by activated brown fat to further reduce hypercholesterolemia and atherosclerosis. Atherosclerosis 267, 116–126 (2017).

    CAS  PubMed  Google Scholar 

  172. Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017).

    CAS  PubMed  Google Scholar 

  173. Markus, M. R. et al. Changes in body weight and composition are associated with changes in left ventricular geometry and function in the general population: SHIP (Study of Health in Pomerania). Circ. Cardiovasc. Imag. 10, e005544 (2017).

    Google Scholar 

  174. Amor, S. et al. Study of insulin vascular sensitivity in aortic rings and endothelial cells from aged rats subjected to caloric restriction: role of perivascular adipose tissue. Exp. Gerontol. 109, 126–136 (2017).

    PubMed  Google Scholar 

  175. Kim, K. H. et al. Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage. Cell Res. 27, 1309–1326 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  176. Araujo, H. N. et al. Anti-contractile effects of perivascular adipose tissue in thoracic aorta from rats fed a high-fat diet: role of aerobic exercise training. Clin. Exp. Pharmacol. Physiol. 45, 293–302 (2018).

    CAS  PubMed  Google Scholar 

  177. Khoo, J. et al. Exercise-induced weight loss is more effective than dieting for improving adipokine profile, insulin resistance, and inflammation in obese men. Int. J. Sport Nutr. Exercise Metabolism 25, 566–575 (2015).

    Google Scholar 

  178. Ross, R. et al. Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Ann. Intern. Med. 133, 92–103 (2000).

    CAS  PubMed  Google Scholar 

  179. Maillard, F., Pereira, B. & Boisseau, N. Effect of High-intensity interval training on total, abdominal and visceral fat mass: a meta-analysis. Sports Med. 48, 269–288 (2018).

    PubMed  Google Scholar 

  180. Dias, K. A. et al. Effect of high-intensity interval training on fitness, fat mass and cardiometabolic biomarkers in children with obesity: a randomised controlled trial. Sports Med. 48, 733–746 (2018).

    PubMed  Google Scholar 

  181. Quist, J. S. et al. Effects of active commuting and leisure-time exercise on fat loss in women and men with overweight and obesity: a randomized controlled trial. Int. J. Obes. 42, 469–478 (2017).

    Google Scholar 

  182. Schauer, P. R. et al. Bariatric surgery versus intensive medical therapy for diabetes - 5-year outcomes. N. Engl. J. Med. 376, 641–651 (2017).

    PubMed  PubMed Central  Google Scholar 

  183. Adams, T. D. et al. Weight and metabolic outcomes 12 years after gastric bypass. N. Engl. J. Med. 377, 1143–1155 (2017).

    PubMed  PubMed Central  Google Scholar 

  184. Salehi, M., Prigeon, R. L. & D’Alessio, D. A. Gastric bypass surgery enhances glucagon-like peptide 1-stimulated postprandial insulin secretion in humans. Diabetes 60, 2308–2314 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  185. Frikke-Schmidt, H. et al. Weight loss independent changes in adipose tissue macrophage and T cell populations after sleeve gastrectomy in mice. Mol. Metab. 6, 317–326 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Hoffstedt, J. et al. Long-term Protective changes in adipose tissue after gastric bypass. Diabetes Care 40, 77–84 (2017).

    CAS  PubMed  Google Scholar 

  187. De Matteis, R. et al. Exercise as a new physiological stimulus for brown adipose tissue activity. Nutr. Metab. Cardiovasc. Dis. 23, 582–590 (2013).

    PubMed  Google Scholar 

  188. Barquissau, V. et al. Caloric restriction and diet-induced weight loss do not induce browning of human subcutaneous white adipose tissue in women and men with obesity. Cell Rep. 22, 1079–1089 (2018).

    CAS  PubMed  Google Scholar 

  189. Tsiloulis, T. et al. No evidence of white adipocyte browning after endurance exercise training in obese men. Int. J. Obes. 42, 721–727 (2017).

    Google Scholar 

  190. Vosselman, M. J. et al. Low brown adipose tissue activity in endurance-trained compared with lean sedentary men. Int. J. Obes. 39, 1696–1702 (2015).

    CAS  Google Scholar 

  191. Seki, T. et al. Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning. J. Exp. Med. 215, 611–626 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  192. Wang, B. et al. Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRalpha(+) adipose progenitors. Cell Discov. 3, 17036 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  193. Oguri, Y. et al. Tetrahydrobiopterin activates brown adipose tissue and regulates systemic energy metabolism. JCI Insight 2, 91981 (2017).

    PubMed  Google Scholar 

  194. Broeders, E. P. et al. Thyroid hormone activates brown adipose tissue and increases non-shivering thermogenesis — a cohort study in a group of thyroid carcinoma patients. PLOS ONE 11, e0145049 (2016).

    PubMed  PubMed Central  Google Scholar 

  195. Cypess, A. M. et al. Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab. 21, 33–38 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  196. Xue, Y., Xu, X., Zhang, X. Q., Farokhzad, O. C. & Langer, R. Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles. Proc. Natl Acad. Sci. USA 113, 5552–5557 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  197. Cui, X. et al. Exosomes from adipose-derived mesenchymal stem cells protect the myocardium against ischemia/reperfusion injury through Wnt/beta-catenin signaling pathway. J. Cardiovasc. Pharmacol. 70, 225–231 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  198. Schenke-Layland, K. et al. Adipose tissue-derived cells improve cardiac function following myocardial infarction. J. Surg. Res. 153, 217–223 (2009).

    CAS  PubMed  Google Scholar 

  199. Bobi, J. et al. Intracoronary administration of allogeneic adipose tissue-derived mesenchymal stem cells improves myocardial perfusion but not left ventricle function, in a translational model of acute myocardial infarction. J. Am. Heart Assoc. 6, e005771 (2017).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

E.K.O. receives support from the A.G. Leventis Foundation. C.A. received funding from the British Heart Foundation (FS/16/15/32047 and TG/16/3/32687), the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Novo Nordisk Foundation (NNF15CC0018486).

Reviewer information

Nature Reviews Cardiology thanks J. Eckel, G. Iacobellis, H. Morawietz and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information

Authors and Affiliations

Authors

Contributions

E.K.O. performed the literature review, prepared the figures and tables and wrote the manuscript before submission. C.A. provided scientific direction and wrote and reviewed the manuscript before submission.

Corresponding author

Correspondence to Charalambos Antoniades.

Ethics declarations

Competing interests

The methods for analysis of perivascular Fat Attenuation Index described in this manuscript are subject to patent applications (PCT/GB2015/052359 and PCT/GB2017/053262). C.A. is a founder and shareholder of Caristo Diagnostics, a CT-image analysis company. C.A. has received research funding from Novo Nordisk and Sanofi and a consultancy fee from Mitsubishi Tanabe.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Visceral adipose tissue

(VAT). Adipose tissue surrounding the visceral organs in the thorax and abdomen, including fat in the omental and mesenteric peritoneal folds (omental/mesenteric adipose tissue), around the kidneys in the retroperitoneal space (perirenal adipose tissue) and epicardial, pericardial and other depots.

Epicardial adipose tissue

(EAT). The adipose tissue layer that lies between the surface of the heart and the visceral pericardium.

Pericardial adipose tissue

The adipose tissue layer located on the external surface of the parietal pericardium.

White adipose tissue

(WAT). The predominant adipose tissue type found in the human body, which is responsible for energy storage in the form of triglycerides and energy supply to peripheral tissues through regulated release of free fatty acids.

Brown adipose tissue

(BAT). A distinct, metabolically active adipose tissue phenotype that is found predominantly in the interscapular and supraclavicular regions in humans and is involved in thermoregulatory thermogenesis.

Beige adipose tissue

Also known as brite adipose tissue; an inducible, brown-like adipose tissue phenotype, which is normally found interspersed in white adipose tissue depots.

Adipocytokines

A range of bioactive molecules secreted by various cell types found in the adipose tissue (such as adipocytes and stromal cells) that exert autocrine, paracrine and endocrine effects on both the adipose and the peripheral tissues.

Ectopic fat

Fat stored in tissues other than the adipose tissue that normally contain small amounts of fat, such as the heart, liver and muscles.

Perivascular adipose tissue

(PVAT). Adipose tissue surrounding the vessels that is often contiguous to the outer adventitial layer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oikonomou, E.K., Antoniades, C. The role of adipose tissue in cardiovascular health and disease. Nat Rev Cardiol 16, 83–99 (2019). https://doi.org/10.1038/s41569-018-0097-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41569-018-0097-6

This article is cited by

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