Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2015, Article ID 970375, 12 pages
http://dx.doi.org/10.1155/2015/970375
Review Article

Impaired Adipose Tissue Expandability and Lipogenic Capacities as Ones of the Main Causes of Metabolic Disorders

1Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Complejo Hospitalario de Málaga (Virgen de la Victoria), Universidad de Málaga, 29010 Málaga, Spain
2Ciber Fisiopatología de la Obesidad y Nutrición (CIBEROBN), 28029 Madrid, Spain

Received 26 November 2014; Revised 15 March 2015; Accepted 18 March 2015

Academic Editor: Pedro M. Geraldes

Copyright © 2015 Isabel Moreno-Indias and Francisco José Tinahones. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Ng, T. Fleming, M. Robinson et al., “Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013,” The Lancet, vol. 384, no. 9945, pp. 766–781, 2014. View at Publisher · View at Google Scholar
  2. J. Chen, Y. Meng, J. Zhou et al., “Identifying candidate genes for type 2 diabetes mellitus and obesity through gene expression profiling in multiple tissues or cells,” Journal of Diabetes Research, vol. 2013, Article ID 970435, 9 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  3. B.-C. Lee and J. Lee, “Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance,” Biochimica et Biophysica Acta—Molecular Basis of Disease, vol. 1842, no. 3, pp. 446–462, 2014. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Bastien, P. Poirier, I. Lemieux, and J.-P. Després, “Overview of epidemiology and contribution of obesity to cardiovascular disease,” Progress in Cardiovascular Diseases, vol. 56, no. 4, pp. 369–381, 2014. View at Publisher · View at Google Scholar · View at Scopus
  5. R. Loomba and A. J. Sanyal, “The global NAFLD epidemic,” Nature Reviews Gastroenterology and Hepatology, vol. 10, no. 11, pp. 686–690, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. J. A. Ligibel, C. M. Alfano, K. S. Courneya et al., “American Society of Clinical Oncology position statement on obesity and cancer,” Journal of Clinical Oncology, vol. 32, no. 31, pp. 3568–3574, 2014. View at Publisher · View at Google Scholar
  7. T. Fall and E. Ingelsson, “Genome-wide association studies of obesity and metabolic syndrome,” Molecular and Cellular Endocrinology, vol. 382, no. 1, pp. 740–757, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. E. Ginter and V. Simko, “Type 2 diabetes mellitus, pandemic in 21st century,” Advances in Experimental Medicine and Biology, vol. 771, pp. 42–50, 2012. View at Google Scholar · View at Scopus
  9. D. Vistisen, D. R. Witte, A. G. Tabák et al., “Patterns of obesity development before the diagnosis of type 2 diabetes: the Whitehall II cohort study,” PLoS Medicine, vol. 11, no. 2, Article ID e1001602, 2014. View at Publisher · View at Google Scholar
  10. S. A. Brethauer, A. Aminian, H. Romero-Talamás et al., “Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus,” Annals of Surgery, vol. 258, no. 4, pp. 628–636, 2013. View at Publisher · View at Google Scholar · View at Scopus
  11. S. Lee, A. R. Deldin, D. White et al., “Aerobic exercise but not resistance exercise reduces intrahepatic lipid content and visceral fat and improves insulin sensitivity in obese adolescent girls: a randomized controlled trial,” American Journal of Physiology: Endocrinology and Metabolism, vol. 305, no. 10, pp. E1222–E1229, 2013. View at Publisher · View at Google Scholar · View at Scopus
  12. T. Romacho, M. Elsen, D. Röhrborn, and J. Eckel, “Adipose tissue and its role in organ crosstalk,” Acta Physiologica, vol. 210, no. 4, pp. 733–753, 2014. View at Publisher · View at Google Scholar
  13. J.-P. Després and I. Lemieux, “Abdominal obesity and metabolic syndrome,” Nature, vol. 444, no. 7121, pp. 881–887, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Blüher, “The distinction of metabolically ‘healthy’ from ‘unhealthy’ obese individuals,” Current Opinion in Lipidology, vol. 21, no. 1, pp. 38–43, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. P. Patel and N. Abate, “Body fat distribution and insulin resistance,” Nutrients, vol. 5, no. 6, pp. 2019–2027, 2013. View at Publisher · View at Google Scholar · View at Scopus
  16. I. Moreno-Indias, F. Cardona, F. J. Tinahones, and M. I. Queipo-Ortuño, “Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus,” Frontiers in Microbiology, vol. 5, article 190, 2014. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Blüher, “Adipose tissue dysfunction contributes to obesity related metabolic diseases,” Best Practice & Research: Clinical Endocrinology & Metabolism, vol. 27, no. 2, pp. 163–177, 2013. View at Publisher · View at Google Scholar · View at Scopus
  18. L. Lionetti, M. P. Mollica, A. Lombardi, G. Cavaliere, G. Gifuni, and A. Barletta, “From chronic overnutrition to insulin resistance: the role of fat-storing capacity and inflammation,” Nutrition, Metabolism and Cardiovascular Diseases, vol. 19, no. 2, pp. 146–152, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. J. V. Neel, “Diabetes mellitus: a ‘thrifty’ genotype rendered detrimental by ‘progress’?” American Journal of Human Genetics, vol. 14, no. 4, pp. 353–362, 1962. View at Google Scholar · View at Scopus
  20. F. Ameer, L. Scandiuzzi, S. Hasnain, H. Kalbacher, and N. Zaidi, “De novo lipogenesis in health and disease,” Metabolism: Clinical and Experimental, vol. 63, no. 7, pp. 895–902, 2014. View at Publisher · View at Google Scholar · View at Scopus
  21. R. V. Farese Jr., R. Zechner, C. B. Newgard, and T. C. Walther, “The problem of establishing relationships between hepatic steatosis and hepatic insulin resistance,” Cell Metabolism, vol. 15, no. 5, pp. 570–573, 2012. View at Publisher · View at Google Scholar · View at Scopus
  22. G. Boden, P. Cheung, K. Kresge, C. Homko, B. Powers, and L. Ferrer, “Insulin resistance is associated with diminished endoplasmic reticulum stress responses in adipose tissue of healthy and diabetic subjects,” Diabetes, vol. 63, no. 9, pp. 2977–2983, 2014. View at Publisher · View at Google Scholar
  23. S. Pereira, D. M. Breen, A. E. Naassan et al., “In vivo effects of polyunsaturated, monounsaturated, and saturated fatty acids on hepatic and peripheral insulin sensitivity,” Metabolism: Clinical and Experimental, vol. 64, no. 2, pp. 315–322, 2015. View at Publisher · View at Google Scholar
  24. J. Boon, A. J. Hoy, R. Stark et al., “Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance,” Diabetes, vol. 62, no. 2, pp. 401–410, 2013. View at Publisher · View at Google Scholar · View at Scopus
  25. I. J. Lodhi, L. Yin, A. P. L. Jensen-Urstad et al., “Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARγ activation to decrease diet-induced obesity,” Cell Metabolism, vol. 16, no. 2, pp. 189–201, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. K. Minehira, N. Vega, H. Vidal, K. Acheson, and L. Tappy, “Effect of carbohydrate overfeeding on whole body macronutrient metabolism and expression of lipogenic enzymes in adipose tissue of lean and overweight humans,” International Journal of Obesity, vol. 28, no. 10, pp. 1291–1298, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. R. H. Unger, G. O. Clark, P. E. Scherer, and L. Orci, “Lipid homeostasis, lipotoxicity and the metabolic syndrome,” Biochimica et Biophysica Acta, vol. 1801, no. 3, pp. 209–214, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. F. J. Ortega, D. Mayas, J. M. Moreno-Navarrete et al., “The gene expression of the main lipogenic enzymes is downregulated in visceral adipose tissue of obese subjects,” Obesity, vol. 18, no. 1, pp. 13–20, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. O. Poulain-Godefroy, C. Lecoeur, F. Pattou, G. Frühbeck, and P. Froguel, “Inflammation is associated with a decrease of lipogenic factors in omental fat in women,” American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 295, no. 1, pp. R1–R7, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Chen, Y. Meng, J. Zhou et al., “Identifying candidate genes for type 2 diabetes mellitus and obesity through gene expression profiling in multiple tissues or cells,” Journal of Diabetes Research, vol. 2013, Article ID 970435, 9 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  31. M. P. Keller and A. D. Attie, “Physiological insights gained from gene expression analysis in obesity and diabetes,” Annual Review of Nutrition, vol. 30, pp. 341–364, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. T.-A. Cock, S. M. Houten, and J. Auwerx, “Peroxisome proliferator-activated receptor-γ: too much of a good thing causes harm,” EMBO Reports, vol. 5, no. 2, pp. 142–147, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Macias-Gonzalez, F. Cardona, M. Queipo-Ortuño, R. Bernal, M. Martin, and F. J. Tinahones, “PPARγ mRNA expression is reduced in peripheral blood mononuclear cells after fat overload in patients with metabolic syndrome,” Journal of Nutrition, vol. 138, no. 5, pp. 903–907, 2008. View at Google Scholar · View at Scopus
  34. S. Rodriguez-Cuenca, S. Carobbio, V. R. Velagapudi et al., “Peroxisome proliferator-activated receptor gamma-dependent regulation of lipolytic nodes and metabolic flexibility,” Molecular and Cellular Biology, vol. 32, no. 8, pp. 1555–1565, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. E. Garcia-Fuentes, M. Murri, L. Garrido-Sanchez et al., “PPARγ expression after a high-fat meal is associated with plasma superoxide dismutase activity in morbidly obese persons,” Obesity, vol. 18, no. 5, pp. 952–958, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. M. MacIas-Gonzalez, I. Moreno-Santos, J. M. García-Almeida, F. J. Tinahones, and E. Garcia-Fuentes, “PPARγ2 protects against obesity by means of a mechanism that mediates insulin resistance,” European Journal of Clinical Investigation, vol. 39, no. 11, pp. 972–979, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. B. M. Spiegelman, “PPAR-gamma: adipogenic regulator and thiazolidinedione receptor,” Diabetes, vol. 47, no. 4, pp. 507–514, 1998. View at Publisher · View at Google Scholar · View at Scopus
  38. F. B. Hillgartner, L. M. Salati, and A. G. Goodridge, “Physiological and molecular mechanisms involved in nutritional regulation of fatty acid synthesis,” Physiological Reviews, vol. 75, no. 1, pp. 47–76, 1995. View at Google Scholar · View at Scopus
  39. M. D. Mayas, F. J. Ortega, M. MacÍas-Gonzlez et al., “Inverse relation between FASN expression in human adipose tissue and the insulin resistance level,” Nutrition & Metabolism, vol. 7, article 3, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. M. D. Mayas, F. J. Ortega, R. Gómez-Huelgas, N. Roca, J. M. Fernández-Real, and F. J. Tinahones, “Decrease in FASN expression in adipose tissue of hypertensive individuals,” American Journal of Hypertension, vol. 22, no. 12, pp. 1258–1262, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Cabassi and S. Tedeschi, “Zinc-α2-glycoprotein as a marker of fat catabolism in humans,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 16, no. 3, pp. 267–271, 2013. View at Publisher · View at Google Scholar · View at Scopus
  42. S. T. Russell, T. P. Zimmerman, B. A. Domin, and M. J. Tisdale, “Induction of lipolysis in vitro and loss of body fat in vivo by zinc-α2-glycoprotein,” Biochimica et Biophysica Acta, vol. 1636, no. 1, pp. 59–68, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. L. Garrido-Sánchez, E. García-Fuentes, D. Fernández-García et al., “Zinc-alpha 2-glycoprotein gene expression in adipose tissue is related with insulin resistance and lipolytic genes in morbidly obese patients,” PLoS ONE, vol. 7, no. 3, Article ID e33264, 2012. View at Publisher · View at Google Scholar · View at Scopus
  44. L. Makowski and G. S. Hotamisligil, “Fatty acid binding proteins—the evolutionary crossroads of inflammatory and metabolic responses,” The Journal of Nutrition, vol. 134, no. 9, pp. 2464s–2468s, 2004. View at Google Scholar · View at Scopus
  45. M. I. Queipo-Ortuño, X. Escoté, V. Ceperuelo-Mallafré et al., “FABP4 dynamics in obesity: discrepancies in adipose tissue and liver expression regarding circulating plasma levels,” PLoS ONE, vol. 7, no. 11, Article ID e48605, 2012. View at Publisher · View at Google Scholar · View at Scopus
  46. B. Sánchez-Solana, J. Laborda, and V. Baladrón, “Mouse resistin modulates adipogenesis and glucose uptake in 3T3-L1 preadipocytes through the ROR1 receptor,” Molecular Endocrinology, vol. 26, no. 1, pp. 110–127, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. B. Meissburger, J. Ukropec, E. Roeder et al., “Adipogenesis and insulin sensitivity in obesity are regulated by retinoid-related orphan receptor gamma,” EMBO Molecular Medicine, vol. 3, no. 11, pp. 637–651, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. F. J. Tinahones, I. Moreno-Santos, J. Vendrell et al., “The retinoic acid receptor-related orphan nuclear receptor γ1 (RORγ1): a novel player determinant of insulin sensitivity in morbid obesity,” Obesity, vol. 20, no. 3, pp. 488–497, 2012. View at Publisher · View at Google Scholar · View at Scopus
  49. M. T. Flowers and J. M. Ntambi, “Stearoyl-CoA desaturase and its relation to high-carbohydrate diets and obesity,” Biochimica et Biophysica Acta, vol. 1791, no. 2, pp. 85–91, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. D. Mauvoisin and C. Mounier, “Hormonal and nutritional regulation of SCD1 gene expression,” Biochimie, vol. 93, no. 1, pp. 78–86, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. J. M. Ntambi, M. Miyazaki, J. P. Stoehr et al., “Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 17, pp. 11482–11486, 2002. View at Publisher · View at Google Scholar · View at Scopus
  52. S. García-Serrano, I. Moreno-Santos, L. Garrido-Sánchez et al., “Stearoyl-CoA desaturase-1 is associated with insulin resistance in morbidly obese subjects,” Molecular Medicine, vol. 17, no. 3-4, pp. 273–280, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. S. Carobbio, R. M. Hagen, C. J. Lelliott et al., “Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity,” Diabetes, vol. 62, no. 11, pp. 3697–3708, 2013. View at Publisher · View at Google Scholar · View at Scopus
  54. S. Martin and R. G. Parton, “Lipid droplets: a unified view of a dynamic organelle,” Nature Reviews Molecular Cell Biology, vol. 7, no. 5, pp. 373–378, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. M. R. Pulido, A. Diaz-Ruiz, Y. Jiménez-Gómez et al., “Rab18 dynamics in adipocytes in relation to lipogenesis, lipolysis and obesity,” PLoS ONE, vol. 6, no. 7, Article ID e22931, 2011. View at Publisher · View at Google Scholar · View at Scopus
  56. S. Martin, K. Driessen, S. J. Nixon, M. Zerial, and R. G. Parton, “Regulated localization of Rab18 to lipid droplets: effects of lipolytic stimulation and inhibition of lipid droplet catabolism,” The Journal of Biological Chemistry, vol. 280, no. 51, pp. 42325–42335, 2005. View at Publisher · View at Google Scholar · View at Scopus
  57. M. R. Pulido, Y. Rabanal-Ruiz, F. Almabouada et al., “Nutritional, hormonal, and depot-dependent regulation of the expression of the small GTPase Rab18 in rodent adipose tissue,” Journal of Molecular Endocrinology, vol. 50, no. 1, pp. 19–29, 2013. View at Publisher · View at Google Scholar · View at Scopus
  58. S. J. Hill, T. Rolland, G. Adelmant et al., “Systematic screening reveals a role for BRCA1 in the response to transcription-associated DNA damage,” Genes & Development, vol. 28, no. 17, pp. 1957–1975, 2014. View at Publisher · View at Google Scholar
  59. M. Song, K. Hakala, S. T. Weintraub, and Y. Shiio, “Quantitative proteomic identification of the BRCA1 ubiquitination substrates,” Journal of Proteome Research, vol. 10, no. 11, pp. 5191–5198, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. H. Ray, K. Moreau, E. Dizin, I. Callebaut, and N. D. Venezia, “ACCA phosphopeptide recognition by the BRCT repeats of BRCA1,” Journal of Molecular Biology, vol. 359, no. 4, pp. 973–982, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. F. J. Ortega, J. M. Moreno-Navarrete, D. Mayas et al., “Breast cancer 1 (BrCa1) may be behind decreased lipogenesis in adipose tissue from obese subjects,” PLoS ONE, vol. 7, no. 5, Article ID e33233, 2012. View at Publisher · View at Google Scholar · View at Scopus
  62. G. H. Goossens, “The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance,” Physiology & Behavior, vol. 94, no. 2, pp. 206–218, 2008. View at Publisher · View at Google Scholar · View at Scopus
  63. K. L. Spalding, E. Arner, P. O. Westermark et al., “Dynamics of fat cell turnover in humans,” Nature, vol. 453, no. 7196, pp. 783–787, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. S. de Ferranti and D. Mozaffarian, “The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences,” Clinical Chemistry, vol. 54, no. 6, pp. 945–955, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. R. Drolet, C. Richard, A. D. Sniderman et al., “Hypertrophy and hyperplasia of abdominal adipose tissues in women,” International Journal of Obesity, vol. 32, no. 2, pp. 283–291, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. M. M. Ibrahim, “Subcutaneous and visceral adipose tissue: structural and functional differences,” Obesity Reviews, vol. 11, no. 1, pp. 11–18, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. J. Hoffstedt, E. Arner, H. Wahrenberg et al., “Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity,” Diabetologia, vol. 53, no. 12, pp. 2496–2503, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. A. Veilleux, M. Caron-Jobin, S. Noël, P. Y. Laberge, and A. Tchernof, “Visceral adipocyte hypertrophy is associated with dyslipidemia independent of body composition and fat distribution in women,” Diabetes, vol. 60, no. 5, pp. 1504–1511, 2011. View at Publisher · View at Google Scholar · View at Scopus
  69. F. J. Tinahones, L. Garrido-Sanchez, M. Miranda et al., “Obesity and insulin resistance-related changes in the expression of lipogenic and lipolytic genes in morbidly obese subjects,” Obesity Surgery, vol. 20, no. 11, pp. 1559–1567, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. C. Y. Tan and A. Vidal-Puig, “Adipose tissue expandability: the metabolic problems of obesity may arise from the inability to become more obese,” Biochemical Society Transactions, vol. 36, no. 5, pp. 935–940, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. S. Virtue and A. Vidal-Puig, “Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome—an allostatic perspective,” Biochimica et Biophysica Acta—Molecular and Cell Biology of Lipids, vol. 1801, no. 3, pp. 338–349, 2010. View at Publisher · View at Google Scholar · View at Scopus
  72. J. K. Sethi and A. J. Vidal-Puig, “Thematic review series: adipocyte Biology. Adipose tissue function and plasticity orchestrate nutritional adaptation,” Journal of Lipid Research, vol. 48, no. 6, pp. 1253–1262, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. M. Laudes, “Role of WNT signalling in the determination of human mesenchymal stem cells into preadipocytes,” Journal of Molecular Endocrinology, vol. 46, no. 2, pp. R65–R72, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. S. E. Jones and C. Jomary, “Secreted Frizzled-related proteins: searching for relationships and patterns,” BioEssays, vol. 24, no. 9, pp. 811–820, 2002. View at Publisher · View at Google Scholar · View at Scopus
  75. A. Ehrlund, N. Mejhert, S. Lorente-Cebrián et al., “Characterization of the Wnt inhibitors secreted frizzled-related proteins (SFRPs) in human adipose tissue,” Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 3, pp. E503–E508, 2013. View at Publisher · View at Google Scholar · View at Scopus
  76. N. Ouchi, A. Higuchi, K. Ohashi et al., “Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity,” Science, vol. 329, no. 5990, pp. 454–457, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. C. Lagathu, C. Christodoulides, C. Y. Tan et al., “Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity,” International Journal of Obesity, vol. 34, no. 12, pp. 1695–1705, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. F. J. Ortega, A. Vazquez-Martin, J.-M. Moreno-Navarrete et al., “Thyroid hormone responsive Spot 14 increases during differentiation of human adipocytes and its expression is down-regulated in obese subjects,” International Journal of Obesity, vol. 34, no. 3, pp. 487–499, 2010. View at Publisher · View at Google Scholar · View at Scopus
  79. S. Baglioni, M. Francalanci, R. Squecco et al., “Characterization of human adult stem-cell populations isolated from visceral and subcutaneous adipose tissue,” The FASEB Journal, vol. 23, no. 10, pp. 3494–3505, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. P. Isakson, A. Hammarstedt, B. Gustafson, and U. Smith, “Impaired preadipocyte differentiation in human abdominal obesity: role of Wnt, tumor necrosis factor-α, and inflammation,” Diabetes, vol. 58, no. 7, pp. 1550–1557, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. K. Cleveland-Donovan, L. A. Maile, W. G. Tsiaras, T. Tchkonia, J. L. Kirkland, and C. M. Boney, “IGF-I activation of the AKT pathway is impaired in visceral but not subcutaneous preadipocytes from obese subjects,” Endocrinology, vol. 151, no. 8, pp. 3752–3763, 2010. View at Publisher · View at Google Scholar · View at Scopus
  82. M. Roldan, M. Macias-Gonzalez, R. Garcia, F. J. Tinahones, and M. Martin, “Obesity short-circuits stemness gene network in human adipose multipotent stem cells,” The FASEB Journal, vol. 25, no. 12, pp. 4111–4126, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Virtue and A. Vidal-Puig, “It's not how fat you are, it's what you do with it that counts,” PLoS Biology, vol. 6, no. 9, article e237, 2008. View at Publisher · View at Google Scholar · View at Scopus
  84. A. Sorisky, “Clinical implications of adipose tissue remodelling: adipogenesis and apoptosis,” Canadian Journal of Diabetes, vol. 26, no. 3, pp. 232–240, 2002. View at Google Scholar
  85. S. Cinti, G. Mitchell, G. Barbatelli et al., “Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans,” Journal of Lipid Research, vol. 46, no. 11, pp. 2347–2355, 2005. View at Publisher · View at Google Scholar · View at Scopus
  86. M. Keuper, M. Blüher, M. R. Schön et al., “An inflammatory micro-environment promotes human adipocyte apoptosis,” Molecular and Cellular Endocrinology, vol. 339, no. 1-2, pp. 105–113, 2011. View at Publisher · View at Google Scholar · View at Scopus
  87. P. Arner and K. L. Spalding, “Fat cell turnover in humans,” Biochemical and Biophysical Research Communications, vol. 396, no. 1, pp. 101–104, 2010. View at Publisher · View at Google Scholar · View at Scopus
  88. F. J. Tinahones, L. C. Aragüez, M. Murri et al., “Caspase induction and BCL2 inhibition in human adipose tissue: a potential relationship with insulin signaling alteration,” Diabetes Care, vol. 36, no. 3, pp. 513–521, 2013. View at Publisher · View at Google Scholar · View at Scopus
  89. M. R. Chacón, C. Richart, J. M. Gómez et al., “Expression of TWEAK and its receptor Fn14 in human subcutaneous adipose tissue. Relationship with other inflammatory cytokines in obesity,” Cytokine, vol. 33, no. 3, pp. 129–137, 2006. View at Publisher · View at Google Scholar · View at Scopus
  90. J. Vendrell, E. Maymó-Masip, F. Tinahones et al., “Tumor necrosis-like weak inducer of apoptosis as a proinflammatory cytokine in human adipocyte cells: up-regulation in severe obesity is mediated by inflammation but not hypoxia,” Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 6, pp. 2983–2992, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. E. Maymó-Masip, S. Fernández-Veledo, A. G. España et al., “The rise of soluble TWEAK levels in severely obese subjects after bariatric surgery may affect adipocyte-cytokine production induced by TNFα,” The Journal of Clinical Endocrinology & Metabolism, vol. 98, no. 8, pp. E1323–E1333, 2013. View at Publisher · View at Google Scholar · View at Scopus
  92. S. Bernardi, G. Zauli, C. Tikellis et al., “TNF-related apoptosis-inducing ligand significantly attenuates metabolic abnormalities in high-fat-fed mice reducing adiposity and systemic inflammation,” Clinical Science, vol. 123, no. 9, pp. 547–555, 2012. View at Publisher · View at Google Scholar · View at Scopus
  93. H. H. Harith, M. J. Morris, and M. M. Kavurma, “On the TRAIL of obesity and diabetes,” Trends in Endocrinology & Metabolism, vol. 24, no. 11, pp. 578–587, 2013. View at Publisher · View at Google Scholar · View at Scopus
  94. M. Keuper, I. Wernstedt Asterholm, P. E. Scherer et al., “TRAIL (TNF-related apoptosis-inducing ligand) regulates adipocyte metabolism by caspase-mediated cleavage of PPARgamma,” Cell death & disease, vol. 4, article e474, 2013. View at Publisher · View at Google Scholar · View at Scopus
  95. S. Ledoux, I. Queguiner, S. Msika et al., “Angiogenesis associated with visceral and subcutaneous adipose tissue in severe human obesity,” Diabetes, vol. 57, no. 12, pp. 3247–3257, 2008. View at Publisher · View at Google Scholar · View at Scopus
  96. Y. Cao, “Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases,” Nature Reviews Drug Discovery, vol. 9, no. 2, pp. 107–115, 2010. View at Publisher · View at Google Scholar · View at Scopus
  97. S. Wang, X. Li, M. Parra, E. Verdin, R. Bassel-Duby, and E. N. Olson, “Control of endothelial cell proliferation and migration by VEGF signaling to histone deacetylase 7,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 22, pp. 7738–7743, 2008. View at Publisher · View at Google Scholar · View at Scopus
  98. H.-K. Sung, K.-O. Doh, J. E. Son et al., “Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis,” Cell Metabolism, vol. 17, no. 1, pp. 61–72, 2013. View at Publisher · View at Google Scholar · View at Scopus
  99. A. Saiki, F. Watanabe, T. Murano, Y. Miyashita, and K. Shirai, “Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro,” International Journal of Obesity, vol. 30, no. 11, pp. 1676–1684, 2006. View at Publisher · View at Google Scholar · View at Scopus
  100. I. Elias, S. Franckhauser, T. Ferré et al., “Adipose tissue overexpression of vascular endothelial growth factor protects against diet-induced obesity and insulin resistance,” Diabetes, vol. 61, no. 7, pp. 1801–1813, 2012. View at Publisher · View at Google Scholar · View at Scopus
  101. F. J. Tinahones, L. Coín-Aragüez, M. D. Mayas et al., “Obesity-associated insulin resistance is correlated to adipose tissue vascular endothelial growth factors and metalloproteinase levels,” BMC Physiology, vol. 12, no. 1, article 4, 2012. View at Publisher · View at Google Scholar · View at Scopus
  102. H. Wada, S. Ura, S. Kitaoka et al., “Distinct characteristics of circulating vascular endothelial growth factor-A and C levels in human subjects,” PLoS ONE, vol. 6, no. 12, Article ID e29351, 2011. View at Publisher · View at Google Scholar · View at Scopus
  103. P. D. Cani, J. Amar, M. A. Iglesias et al., “Metabolic endotoxemia initiates obesity and insulin resistance,” Diabetes, vol. 56, no. 7, pp. 1761–1772, 2007. View at Publisher · View at Google Scholar · View at Scopus
  104. M. Clemente-Postigo, M. I. Queipo-Ortuño, M. Murri et al., “Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients,” Journal of Lipid Research, vol. 53, no. 5, pp. 973–978, 2012. View at Publisher · View at Google Scholar · View at Scopus
  105. A. M. Caricilli and M. J. A. Saad, “The role of gut microbiota on insulin resistance,” Nutrients, vol. 5, no. 3, pp. 829–851, 2013. View at Publisher · View at Google Scholar · View at Scopus
  106. N. Barbarroja, R. López-Pedrera, M. D. Mayas et al., “The obese healthy paradox: is inflammation the answer?” The Biochemical Journal, vol. 430, no. 1, pp. 141–149, 2010. View at Publisher · View at Google Scholar · View at Scopus
  107. N. Hosogai, A. Fukuhara, K. Oshima et al., “Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation,” Diabetes, vol. 56, no. 4, pp. 901–911, 2007. View at Publisher · View at Google Scholar · View at Scopus
  108. J. Ye, “Emerging role of adipose tissue hypoxia in obesity and insulin resistance,” International Journal of Obesity, vol. 33, no. 1, pp. 54–66, 2009. View at Publisher · View at Google Scholar · View at Scopus
  109. P. Trayhurn, B. Wang, and I. S. Wood, “Hypoxia and the endocrine and signalling role of white adipose tissue,” Archives of Physiology and Biochemistry, vol. 114, no. 4, pp. 267–276, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. J. Ye, “Mechanisms of insulin resistance in obesity,” Frontiers of Medicine in China, vol. 7, no. 1, pp. 14–24, 2013. View at Publisher · View at Google Scholar · View at Scopus
  111. J. Ye and O. P. McGuinness, “Inflammation during obesity is not all bad: evidence from animal and human studies,” American Journal of Physiology: Endocrinology and Metabolism, vol. 304, no. 5, pp. E466–E477, 2013. View at Publisher · View at Google Scholar · View at Scopus