Biology of upper-body and lower-body adipose tissue—link to whole-body phenotypes (original) (raw)

• 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
• 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
• 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
• Wells, J. C. Sexual dimorphism of body composition. Best Pract. Res. Clin. Endocrinol. Metab. 21, 415–430 (2007).
  PubMed Google Scholar
• 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
• Stunkard, A. J., Foch, T. T. & Hrubec, Z. A twin study of human obesity. JAMA 256, 51–54 (1986).
  CAS PubMed Google Scholar
• 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
• Lehtovirta, M. et al. Insulin sensitivity and insulin secretion in monozygotic and dizygotic twins. Diabetologia 43, 285–293 (2000).
  CAS PubMed Google Scholar
• 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
• 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
• 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
• 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
• 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
• 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
• 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.
• Bluher, M. Mechanisms in endocrinology: are metabolically healthy obese individuals really healthy? Eur. J. Endocrinol. http://dx.doi.org/10.1530/EJE-14-0540.
• 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
• 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
• 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
• 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
• Oxford BioBank [online], (2014).
• Kloting, N. et al. Insulin-sensitive obesity. Am. J. Physiol. Endocrinol. Metab. 299, E506–E515 (2010).
  PubMed Google Scholar
• Danforth, E. Jr. Failure of adipocyte differentiation causes type II diabetes mellitus? Nat. Genet. 26, 13 (2000).
  CAS PubMed Google Scholar
• 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
• 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
• 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
• 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
• Spalding, K. L. et al. Dynamics of fat cell turnover in humans. Nature 453, 783–787 (2008).
  CAS PubMed Google Scholar
• 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
• 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
• Billon, N. et al. The generation of adipocytes by the neural crest. Development 134, 2283–2292 (2007).
  CAS PubMed Google Scholar
• Tang, W. et al. White fat progenitor cells reside in the adipose vasculature. Science 322, 583–586 (2008).
  CAS PubMed PubMed Central Google Scholar
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• Yamamoto, Y. et al. Adipose depots possess unique developmental gene signatures. Obesity (Silver Spring) 18, 872–878 (2010).
  CAS Google Scholar
• 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
• 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
• 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
• 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
• Chang, H. Y. Anatomic demarcation of cells: genes to patterns. Science 326, 1206–1207 (2009).
  CAS PubMed Google Scholar
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• Dick, K. J. et al. DNA methylation and body-mass index: a genome-wide analysis. Lancet 383, 1990–1998 (2014).
  CAS PubMed Google Scholar
• Gehrke, S. et al. Epigenetic regulation of depot-specific gene expression in adipose tissue. PLoS ONE 8, e82516 (2013).
  PubMed PubMed Central Google Scholar
• Soshnikova, N. & Duboule, D. Epigenetic regulation of vertebrate Hox genes: a dynamic equilibrium. Epigenetics 4, 537–540 (2009).
  CAS PubMed Google Scholar
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• Marin, P., Rebuffe-Scrive, M., Smith, U. & Bjorntorp, P. Glucose uptake in human adipose tissue. Metabolism 36, 1154–1160 (1987).
  CAS PubMed Google Scholar
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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