Benjamin, E. J. et al. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation 135, e146–e603 (2017).
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).
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).
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).
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).
Britton, K. A. et al. Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality. J. Am. Coll. Cardiol. 62, 921–925 (2013).
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).
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).
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).
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).
Akoumianakis, I. & Antoniades, C. The interplay between adipose tissue and the cardiovascular system: is fat always bad? Cardiovasc. Res. 113, 999–1008 (2017).
Wajchenberg, B. L. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr. Rev. 21, 697–738 (2000).
Iacobellis, G. Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat. Rev. Endocrinol. 11, 363–371 (2015).
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).
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).
Passaro, A. et al. Gene expression regional differences in human subcutaneous adipose tissue. BMC Genomics 18, 202 (2017).
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).
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).
Harms, M. & Seale, P. Brown and beige fat: development, function and therapeutic potential. Nat. Med. 19, 1252–1263 (2013).
Villarroya, F., Cereijo, R., Villarroya, J. & Giralt, M. Brown adipose tissue as a secretory organ. Nat. Rev. Endocrinol. 13, 26–35 (2017).
Stanford, K. I. et al. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J. Clin. Invest. 123, 215–223 (2013).
Gronthos, S. et al. Surface protein characterization of human adipose tissue-derived stromal cells. J. Cell. Physiol. 189, 54–63 (2001).
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).
Srikakulapu, P. et al. Perivascular adipose tissue harbors atheroprotective IgM-producing B cells. Front. Physiol. 8, 719 (2017).
Withers, S. B. et al. Eosinophils are key regulators of perivascular adipose tissue and vascular functionality. Sci. Rep. 7, 44571 (2017).
Zuk, P. A. et al. Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell 13, 4279–4295 (2002).
Tilg, H. & Moschen, A. R. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat. Rev. Immunol. 6, 772–783 (2006).
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).
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).
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).
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).
Rutkowski, J. M., Stern, J. H. & Scherer, P. E. The cell biology of fat expansion. J. Cell Biol. 208, 501–512 (2015).
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).
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).
Weisberg, S. P. et al. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796–1808 (2003).
Cildir, G., Akincilar, S. C. & Tergaonkar, V. Chronic adipose tissue inflammation: all immune cells on the stage. Trends Mol. Med. 19, 487–500 (2013).
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).
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).
Fujisaka, S. et al. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58, 2574–2582 (2009).
Onogi, Y. et al. PDGFRbeta regulates adipose tissue expansion and glucose metabolism via vascular remodeling in diet-induced obesity. Diabetes 66, 1008–1021 (2017).
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).
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).
Halberg, N. et al. Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Mol. Cell. Biol. 29, 4467–4483 (2009).
Escobedo, N. et al. Restoration of lymphatic function rescues obesity in Prox1-haploinsufficient mice. JCI Insight 1, e85096 (2016).
Li, G. et al. Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota. Cell Metab. 26, 672–685 (2017).
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).
Chechi, K. et al. Functional characterization of the Ucp1-associated oxidative phenotype of human epicardial adipose tissue. Sci. Rep. 7, 15566 (2017).
Oikonomou, E. K. & Antoniades, C. Immunometabolic regulation of vascular redox state: the role of adipose tissue. Antioxid. Redox Signal 29, 313–336 (2017).
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).
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).
Weng, C. et al. Effects of chemerin/CMKLR1 in obesity-induced hypertension and potential mechanism. Am. J. Transl Res. 9, 3096–3104 (2017).
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).
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).
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).
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).
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).
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).
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).
Uretsky, S. et al. Obesity paradox in patients with hypertension and coronary artery disease. Am. J. Med. 120, 863–870 (2007).
Khawaja, T. et al. Epicardial fat volume in patients with left ventricular systolic dysfunction. Am. J. Cardiol. 108, 397–401 (2011).
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).
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).
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).
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).
Vilahur, G., Ben-Aicha, S. & Badimon, L. New insights into the role of adipose tissue in thrombosis. Cardiovasc. Res. 113, 1046–1054 (2017).
Thomou, T. et al. Adipose-derived circulating mi-RNAs regulate gene expression in other tissues. Nature 542, 450–455 (2017).
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).
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).
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).
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).
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).
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).
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).
Chang, L. et al. Bmal1 in perivascular adipose tissue regulates resting phase blood pressure through transcriptional regulation of angiotensinogen. Circulation 138, 67–79 (2018).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Sweeney, G. Cardiovascular effects of leptin. Nat. Rev. Cardiol. 7, 22–29 (2010).
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).
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).
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).
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).
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).
Fischer, C. et al. A miR-327-FGF10-FGFR2-mediated autocrine signaling mechanism controls white fat browning. Nat. Commun. 8, 2079 (2017).
Icli, B. & Feinberg, M. W. MicroRNAs in dysfunctional adipose tissue: cardiovascular implications. Cardiovasc. Res. 113, 1024–1034 (2017).
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).
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).
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).
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).
Ruan, C. C. et al. Complement-mediated inhibition of adiponectin regulates perivascular inflammation and vascular injury in hypertension. FASEB J. 31, 1120–1129 (2017).
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).
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).
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).
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).
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).
Gao, W. et al. Retinol-binding protein 4 induces cardiomyocyte hypertrophy by activating TLR4/MyD88 pathway. Endocrinology 157, 2282–2293 (2016).
Blumensatt, M. et al. Activin A impairs insulin action in cardiomyocytes via up-regulation of miR-143. Cardiovasc. Res. 100, 201–210 (2013).
Rodriguez-Penas, D. et al. The adipokine chemerin induces apoptosis in cardiomyocytes. Cell Physiol. Biochem. 37, 176–192 (2015).
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).
Sawaki, D. et al. Visceral adipose tissue drives cardiac aging through modulation of fibroblast senescence by osteopontin production. Circulation 138, 809–822 (2018).
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).
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).
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).
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).
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).
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).
Salatzki, J. et al. Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced left ventricular failure. PLOS Genet. 14, e1007171 (2018).
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).
Takaoka, M. et al. Endovascular injury induces rapid phenotypic changes in perivascular adipose tissue. Arterioscler Thromb. Vasc. Biol. 30, 1576–1582 (2010).
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).
Antonopoulos, A. S. et al. Detecting human coronary inflammation by imaging perivascular fat. Sci. Transl Med. 9, eaal2658 (2017).
Liu, D., Ceddia, R. P. & Collins, S. Cardiac natriuretic peptides promote adipose ‘browning’ through mTOR complex-1. Mol. Metab. 9, 192–198 (2018).
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).
Suffee, N. et al. Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria. Proc. Natl Acad. Sci. USA 114, E771–E780 (2017).
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).
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).
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).
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).
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).
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).
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).
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).
Neeland, I. J. et al. Body fat distribution and incident cardiovascular disease in obese adults. J. Am. Coll. Cardiol. 65, 2150–2151 (2015).
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).
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).
Lazaros, G. et al. Prognostic implications of epicardial fat volume quantification in acute pericarditis. Eur. J. Clin. Invest. 47, 129–136 (2017).
Takx, R. A. et al. Supraclavicular brown adipose tissue 18F-FDG uptake and cardiovascular disease. J. Nucl. Med. 57, 1221–1225 (2016).
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).
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).
Kaul, S. et al. Dual-energy X-ray absorptiometry for quantification of visceral fat. Obesity 20, 1313–1318 (2012).
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).
Davidovich, D., Gastaldelli, A. & Sicari, R. Imaging cardiac fat. Eur. Heart J. Cardiovasc. Imag. 14, 625–630 (2013).
Verma, S. K. et al. Differentiating brown and white adipose tissues by high-resolution diffusion NMR spectroscopy. J. Lipid Res. 58, 289–298 (2017).
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).
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).
Ohyama, K. et al. Coronary adventitial and perivascular adipose tissue inflammation in patients with vasospastic angina. J. Am. Coll. Cardiol. 71, 414–425 (2018).
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).
Ganesan, G. et al. Diffuse optical spectroscopic imaging of subcutaneous adipose tissue metabolic changes during weight loss. Int. J. Obes. 40, 1292–1300 (2016).
Dinish, U. S. et al. Diffuse optical spectroscopy and imaging to detect and quantify adipose tissue browning. Sci. Rep. 7, 41357 (2017).
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).
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).
ORIGIN Trials Investigators et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N. Engl. J. Med. 367, 319–328 (2012).
Marso, S. P. et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375, 311–322 (2016).
Green, J. B. et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 373, 232–242 (2015).
Zinman, B. et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N. Engl. J. Med. 373, 2117–2128 (2015).
Iacobellis, G., Mohseni, M., Bianco, S. D. & Banga, P. K. Liraglutide causes large and rapid epicardial fat reduction. Obesity 25, 311–316 (2017).
Lamers, D. et al. Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes 60, 1917–1925 (2011).
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).
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).
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).
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).
Xu, F. et al. GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1. Diabetologia 59, 1059–1069 (2016).
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).
Sato, T. et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc. Diabetol 17, 6 (2018).
Neeland, I. J. et al. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA 308, 1150–1159 (2012).
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).
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).
Kumar, D. et al. Saroglitazar reduces obesity and associated inflammatory consequences in murine adipose tissue. Eur. J. Pharmacol. 822, 32–42 (2018).
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).
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).
Sakaue, T. et al. Perivascular adipose tissue angiotensin II type 1 receptor promotes vascular inflammation and aneurysm formation. Hypertension 70, 780–789 (2017).
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).
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).
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).
Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Schauer, P. R. et al. Bariatric surgery versus intensive medical therapy for diabetes - 5-year outcomes. N. Engl. J. Med. 376, 641–651 (2017).
Adams, T. D. et al. Weight and metabolic outcomes 12 years after gastric bypass. N. Engl. J. Med. 377, 1143–1155 (2017).
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).
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).
Hoffstedt, J. et al. Long-term Protective changes in adipose tissue after gastric bypass. Diabetes Care 40, 77–84 (2017).
De Matteis, R. et al. Exercise as a new physiological stimulus for brown adipose tissue activity. Nutr. Metab. Cardiovasc. Dis. 23, 582–590 (2013).
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).
Tsiloulis, T. et al. No evidence of white adipocyte browning after endurance exercise training in obese men. Int. J. Obes. 42, 721–727 (2017).
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).
Seki, T. et al. Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning. J. Exp. Med. 215, 611–626 (2018).
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).
Oguri, Y. et al. Tetrahydrobiopterin activates brown adipose tissue and regulates systemic energy metabolism. JCI Insight 2, 91981 (2017).
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).
Cypess, A. M. et al. Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab. 21, 33–38 (2015).
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).
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).
Schenke-Layland, K. et al. Adipose tissue-derived cells improve cardiac function following myocardial infarction. J. Surg. Res. 153, 217–223 (2009).
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).