Control of adipocyte differentiation in different fat depots; Implications for pathophysiology or therapy

Frontiers in Endocrinology

Volumn 6, Issue JAN, 2015, Pages

  Ma, Xiuquan ^a,b   Lee, Paul ^a   Chisholm, Donald J ^a   James, David E ^c  

^a GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

^b UNIVERSITY OF SYDNEY   (Australia)

^c UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Adipocyte; Adipocyte differentiation; Adipogenesis; Adipose tissue; Brown adipose tissue; Fat depot; Subcutaneous white adipose tissue; Visceral white adipose tissue

Indexed keywords

ADIPOCYTOKINE; ADIPONECTIN; BONE MORPHOGENETIC PROTEIN; CCAAT ENHANCER BINDING PROTEIN; CCAAT ENHANCER BINDING PROTEIN ALPHA; CCAAT ENHANCER BINDING PROTEIN BETA; CCAAT ENHANCER BINDING PROTEIN DELTA; CREATINE KINASE MM; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; KRUPPEL LIKE FACTOR; LEPTIN; MICRORNA; MYOD PROTEIN; MYOGENIC FACTOR 5; MYOGENIN; MYOSIN LIGHT CHAIN KINASE; NUCLEAR RECEPTOR COACTIVATOR 2; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; STEROID RECEPTOR COACTIVATOR 1; TRANSCRIPTION FACTOR 7 LIKE 1; TRANSCRIPTION FACTOR TWIST; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; UNCOUPLING PROTEIN 1; UNINDEXED DRUG; WNT 1 INDUCIBLE SIGNALING PATHWAY PROTEIN 2; WNT PROTEIN; ZINC FINGER PROTEIN; ZINC FINGER PROTEIN 423; ZINC FINGER PROTEIN 521;

ADIPOCYTE; ADIPOGENESIS; ANGIOGENESIS; BROWN ADIPOSE TISSUE; CARDIOMETABOLIC RISK; CELL DIFFERENTIATION; DIABETES MELLITUS; DYSLIPIDEMIA; FATTY LIVER; GENE MUTATION; GLUCOSE TOLERANCE; HORMONE ACTION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INSULIN SENSITIVITY; LIPID OXIDATION; LIPID STORAGE; OBESITY; PATHOPHYSIOLOGY; PROADIPOCYTE; REGULATORY MECHANISM; REVIEW; THERMOGENESIS; TISSUE EXPANSION; WHITE ADIPOSE TISSUE;

EID: 84926632412     PISSN: None     EISSN: 16642392     Source Type: Journal    
DOI: 10.3389/fendo.2015.00001     Document Type: Review

References (120)

1. Frayn KN, Karpe F. Regulation of human subcutaneous adipose tissue blood flow. Int J Obes (Lond) (2014) 38:1019-26. doi:10.1038/ijo.2013.200
2. Hocking S, Samocha-Bonet D, Milner KL, Greenfield JR, Chisholm DJ. Adiposity and insulin resistance in humans: the role of the different tissue and cellular lipid depots. Endocr Rev (2013) 34:463-500. doi:10.1210/er.2012-1041
3. Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell (2014) 156:20-44. doi:10.1016/j.cell.2013.12.012
4. Kras KM, Hausman DB, Hausman GJ, Martin RJ. Adipocyte development is dependent upon stem cell recruitment and proliferation of preadipocytes. Obes Res (1999) 7:491-7. doi:10.1002/j.1550-8528.1999.tb00438.x
5. Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res (2007) 100:1249-60. doi:10.1161/01.RES.0000265074.83288.09
6. Amos PJ, Shang H, Bailey AM, Taylor A, Katz AJ, Peirce SM. IFATS collection: the role of human adipose-derived stromal cells in inflammatory microvascular remodeling and evidence of a perivascular phenotype. Stem Cells (2008) 26:2682-90. doi:10.1634/stemcells.2008-0030
7. Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell (2008) 3:301-13. doi:10.1016/j.stem.2008.07.003
8. Traktuev DO, Merfeld-Clauss S, Li J, Kolonin M, Arap W, Pasqualini R, et al. A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res (2008) 102:77-85. doi:10.1161/CIRCRESAHA.107.159475
9. Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, et al. White fat progenitor cells reside in the adipose vasculature. Science (2008) 322:583-6. doi:10.1126/science.1156232
10. Gupta RK, Arany Z, Seale P, Mepani RJ, Ye L, Conroe HM, et al. Transcriptional control of preadipocyte determination by Zfp423. Nature (2010) 464:619-23. doi:10.1038/nature08816
11. Gupta RK, Mepani RJ, Kleiner S, Lo JC, Khandekar MJ, Cohen P, et al. Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells. Cell Metab (2012) 15:230-9. doi:10.1016/j.cmet.2012.01.010
12. Tran KV, Gealekman O, Frontini A, Zingaretti MC, Morroni M, Giordano A, et al. The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells. Cell Metab (2012) 15:222-9. doi:10.1016/j.cmet.2012.01.008
13. Huang HY, Song TJ, Li X, Hu LL, He Q, Liu M, et al. BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc Natl Acad Sci U S A (2009) 106:12670-5. doi:10.1073/pnas.0906266106
14. Tsai RY, Reed RR. Identification of DNA recognition sequences and protein interaction domains of the multiple-Zn-finger protein Roaz. Mol Cell Biol (1998) 18:6447-56.
15. Hata A, Seoane J, Lagna G, Montalvo E, Hemmati-Brivanlou A, Massague J. OAZ uses distinct DNA-and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways. Cell (2000) 100:229-40. doi:10.1016/S0092-8674(00)81561-5
16. Festa E, Fretz J, Berry R, Schmidt B, Rodeheffer M, Horowitz M, et al. Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling. Cell (2011) 146:761-71. doi:10.1016/j.cell.2011.07.019
17. Kang S, Akerblad P, Kiviranta R, Gupta RK, Kajimura S, Griffin MJ, et al. Regulation of early adipose commitment by zfp521. PLoS Biol (2012) 10:e1001433. doi:10.1371/journal.pbio.1001433
18. Hammarstedt A, Hedjazifar S, Jenndahl L, Gogg S, Grunberg J, Gustafson B, et al. WISP2 regulates preadipocyte commitment and PPARgamma activation by BMP4. Proc Natl Acad Sci U S A (2013) 110:2563-8. doi:10.1073/pnas.1211255110
19. Cristancho AG, Schupp M, Lefterova MI, Cao S, Cohen DM, Chen CS, et al. Repressor transcription factor 7-like 1 promotes adipogenic competency in precursor cells. Proc Natl Acad Sci U S A (2011) 108:16271-6. doi:10.1073/pnas.1109409108
20. Farmer SR. Transcriptional control of adipocyte formation. Cell Metab (2006) 4:263-73. doi:10.1016/j.cmet.2006.07.001
21. Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol (2006) 7:885-96. doi:10.1038/nrm2066
22. Siersbaek R, Nielsen R, Mandrup S. Transcriptional networks and chromatin remodeling controlling adipogenesis. Trends Endocrinol Metab (2012) 23:56-64. doi:10.1016/j.tem.2011.10.001
23. Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, et al. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell (1999) 3:151-8. doi:10.1016/S1097-2765(00)80306-8
24. Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ, et al. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes Dev (2002) 16:22-6. doi:10.1101/gad.948702
25. Park BO, Ahrends R, Teruel MN. Consecutive positive feedback loops create a bistable switch that controls preadipocyte-to-adipocyte conversion. Cell Rep (2012) 2:976-90. doi:10.1016/j.celrep.2012.08.038
26. Nedergaard J, Bengtsson T, Cannon B. Three years with adult human brown adipose tissue. Ann N Y Acad Sci (2010) 1212:E20-36. doi:10.1111/j.1749-6632.2010.05905.x
27. Richard D, Picard F. Brown fat biology and thermogenesis. Front Biosci (Landmark Ed) (2011) 16:1233-60. doi:10.2741/3786
28. Kajimura S, Seale P, Spiegelman BM. Transcriptional control of brown fat development. Cell Metab (2010) 11:257-62. doi:10.1016/j.cmet.2010.03.005
29. Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature (2008) 454:961-7. doi:10.1038/nature07182
30. Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab (2007) 6:38-54. doi:10.1016/j.cmet.2007.06.001
31. Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni JV, Gygi SP, et al. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature (2009) 460:1154-8. doi:10.1038/nature08262
32. Walden TB, Timmons JA, Keller P, Nedergaard J, Cannon B. Distinct expression of muscle-specific microRNAs (myomirs) in brown adipocytes. J Cell Physiol (2009) 218:444-9. doi:10.1002/jcp.21621
33. Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem (2010) 285:7153-64. doi:10.1074/jbc.M109.053942
34. Walden TB, Hansen IR, Timmons JA, Cannon B, Nedergaard J. Recruited vs. nonrecruited molecular signatures of brown, "brite," and white adipose tissues. Am J Physiol Endocrinol Metab (2012) 302:E19-31. doi:10.1152/ajpendo.00249.2011
35. Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell (2012) 150:366-76. doi:10.1016/j.cell.2012.05.016
36. Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K, et al. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab (2010) 298:E1244-53. doi:10.1152/ajpendo.00600.2009
37. Lee YH, Petkova AP, Mottillo EP, Granneman JG. In vivo identification of bipotential adipocyte progenitors recruited by beta3-adrenoceptor activation and high-fat feeding. Cell Metab (2012) 15:480-91. doi:10.1016/j.cmet.2012.03.009
38. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med (2013) 19:1252-63. doi:10.1038/nm.3361
39. Ussar S, Lee KY, Dankel SN, Boucher J, Haering MF, Kleinridders A, et al. ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes. Sci Transl Med (2014) 6:247ra103. doi:10.1126/scitranslmed.3008490
40. Nishio M, Yoneshiro T, Nakahara M, Suzuki S, Saeki K, Hasegawa M, et al. Production of functional classical brown adipocytes from human pluripotent stem cells using specific hemopoietin cocktail without gene transfer. Cell Metab (2012) 16:394-406. doi:10.1016/j.cmet.2012.08.001
41. Long JZ, Svensson KJ, Tsai L, Zeng X, Roh HC, Kong X, et al. A smooth muscle-like origin for beige adipocytes. Cell Metab (2014) 19:810-20. doi:10.1016/j.cmet.2014.03.025
42. O'Rahilly S, Farooqi IS. Human obesity as a heritable disorder of the central control of energy balance. Int J Obes (2008) 32:S55-61. doi:10.1038/ijo.2008.239
43. Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med (2003) 348:1085-95. doi:10.1056/NEJMoa022050
44. Carey DG, Cowin GJ, Galloway GJ, Jones NP, Richards JC, Biswas N, et al. Effect of rosiglitazone on insulin sensitivity and body composition in type 2 diabetic patients. Obes Res (2002) 10:1008-15. doi:10.1038/oby.2002.137
45. Semple RK, Chatterjee VK, O'Rahilly S. PPAR gamma and human metabolic disease. J Clin Invest (2006) 116:581-9. doi:10.1172/JCI28003
46. Adams M, Montague CT, Prins JB, Holder JC, Smith SA, Sanders L, et al. Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation. J Clin Invest (1997) 100:3149-53. doi:10.1172/JCI119870
47. Piers LS, Rowley KG, Soares MJ, O'Dea K. Relation of adiposity and body fat distribution to body mass index in Australians of Aboriginal and European ancestry. Eur J Clin Nutr (2003) 57:956-63. doi:10.1038/sj.ejcn.1601630
48. Kondalsamy-Chennakesavan S, Hoy WE, Wang Z, Briganti E, Polkinghorne K, Chadban S, et al. Anthropometric measurements of Australian Aboriginal adults living in remote areas: comparison with nationally representative findings. Am J Hum Biol (2008) 20:317-24. doi:10.1002/ajhb.20729
49. Kondalsamy-Chennakesavan S, Hoy WE, Wang Z, Shaw J. Quantifying the excess risk of type 2 diabetes by body habitus measurements among Australian aborigines living in remote areas. Diabetes Care (2008) 31:585-6. doi:10.2337/dc07-1156
50. Nyamdorj R, Pitkaniemi J, Tuomilehto J, Hammar N, Stehouwer CD, Lam TH, et al. Ethnic comparison of the association of undiagnosed diabetes with obesity. Int J Obes (Lond) (2010) 34:332-9. doi:10.1038/ijo.2009.225
51. Oldenburg AR, Delbarre E, Thiede B, Vigouroux C, Collas P. Deregulation of Fragile X-related protein 1 by the lipodystrophic lamin A p.R482W mutation elicits a myogenic gene expression program in preadipocytes. Hum Mol Genet (2014) 23:1151-62. doi:10.1093/hmg/ddt509
52. Carey DG, Nguyen TV, Campbell LV, Chisholm DJ, Kelly P. Genetic influences on central abdominal fat: a twin study. Int J Obes Relat Metab Disord (1996) 20:722-6.
53. Samaras K, Spector TD, Nguyen TV, Baan K, Campbell LV, Kelly PJ. Independent genetic factors determine the amount and distribution of fat in women after the menopause. J Clin Endocrinol Metab (1997) 82:781-5. doi:10.1210/jc.82.3.781
54. Li H, Heilbronn LK, Hu D, Poynten AM, Blackburn MA, Shirkhedkar DP, et al. Islet-1: a potentially important role for an islet cell gene in visceral fat. Obesity (Silver Spring) (2008) 16:356-62. doi:10.1038/oby.2007.76
55. Ma X, Yang P, Kaplan WH, Lee BH, Wu LE, Yang JY, et al. ISL1 regulates peroxisome proliferator-activated receptor gamma activation and early adipogenesis via bone morphogenetic protein 4-dependent and-independent mechanisms. Mol Cell Biol (2014) 34:3607-17. doi:10.1128/MCB.00583-14
56. Lee P, Swarbrick MM, Ho KK. Brown adipose tissue in adult humans: a metabolic renaissance. Endocr Rev (2013) 34:413-38. doi:10.1210/er.2012-1081
57. Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, et al. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell (2014) 156:304-16. doi:10.1016/j.cell.2013.12.021
58. Ho KK, O'Sullivan AJ, Hoffman DM. Metabolic actions of growth hormone in man. Endocr J (1996) 43(Suppl):S57-63. doi:10.1507/endocrj.43.Suppl_S57
59. Poehlman ET, Toth MJ, Gardner AW. Changes in energy balance and body composition at menopause: a controlled longitudinal study. Ann Intern Med (1995) 123:673-5. doi:10.7326/0003-4819-123-9-199511010-00005
60. Lee JY, Takahashi N, Yasubuchi M, Kim YI, Hashizaki H, Kim MJ, et al. Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes. Am J Physiol Cell Physiol (2012) 302:C463-72. doi:10.1152/ajpcell.00010.2011
61. Rodriguez-Cuenca S, Monjo M, Gianotti M, Proenza AM, Roca P. Expression of mitochondrial biogenesis-signaling factors in brown adipocytes is influenced specifically by 17beta-estradiol, testosterone, and progesterone. Am J Physiol Endocrinol Metab (2007) 292:E340-6. doi:10.1152/ajpendo.00175.2006
62. Rodriguez AM, Monjo M, Roca P, Palou A. Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes. Cell Mol Life Sci (2002) 59:1714-23. doi:10.1007/PL00012499
63. Slavin BG, Elias JJ. Morphologic changes in white and brown adipose tissue by insulin, thyroxin and cortisol in organ culture. Anat Rec (1970) 167:213-8. doi:10.1002/ar.1091670209
64. Qiu Y, Nguyen KD, Odegaard JI, Cui X, Tian X, Locksley RM, et al. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell (2014) 157:1292-308. doi:10.1016/j.cell.2014.03.066
65. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature (2012) 481:463-8. doi:10.1038/nature10777
66. Fisher FM, Kleiner S, Douris N, Fox EC, Mepani RJ, Verdeguer F, et al. FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev (2012) 26:271-81. doi:10.1101/gad.177857.111
67. Schulz TJ, Huang P, Huang TL, Xue R, McDougall LE, Townsend KL, et al. Brown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat. Nature (2013) 495:379-83. doi:10.1038/nature11943
68. Rao RR, Long JZ, White JP, Svensson KJ, Lou J, Lokurkar I, et al. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell (2014) 157:1279-91. doi:10.1016/j.cell.2014.03.065
69. Keating SE, Hackett DA, George J, Johnson NA. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol (2012) 57:157-66. doi:10.1016/j.jhep.2012.02.023
70. Matsuzawa Y. The role of fat topology in the risk of disease. Int J Obes (Lond) (2008) 32(Suppl 7):S83-92. doi:10.1038/ijo.2008.243
71. Ismail I, Keating SE, Baker MK, Johnson NA. A systematic review and meta-analysis of the effect of aerobic vs. resistance exercise training on visceral fat. Obes Rev (2012) 13:68-91. doi:10.1111/j.1467-789X.2011.00931.x
72. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev (2004) 84:277-359. doi:10.1152/physrev.00015.2003
73. Cannon B, Jacobsson A, Rehnmark S, Nedergaard J. Signal transduction in brown adipose tissue recruitment: noradrenaline and beyond. Int J Obes Relat Metab Disord (1996) 20(Suppl 3):S36-42.
74. Ye L, Wu J, Cohen P, Kazak L, Khandekar MJ, Jedrychowski MP, et al. Fat cells directly sense temperature to activate thermogenesis. Proc Natl Acad Sci U S A (2013) 110:12480-5. doi:10.1073/pnas.1310261110
75. Carey DG, Jenkins AB, Campbell LV, Freund J, Chisholm DJ. Abdominal fat and insulin resistance in normal and overweight women: direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM. Diabetes (1996) 45:633-8. doi:10.2337/diab.45.5.633
76. Ross R, Aru J, Freeman J, Hudson R, Janssen I. Abdominal adiposity and insulin resistance in obese men. Am J Physiol Endocrinol Metab (2002) 282:E657-63. doi:10.1152/ajpendo.00469.2001
77. Lysaght J, Van Der Stok EP, Allott EH, Casey R, Donohoe CL, Howard JM, et al. Pro-inflammatory and tumour proliferative properties of excess visceral adipose tissue. Cancer Lett (2011) 312:62-72. doi:10.1016/j.canlet.2011.07.034
78. Mathieu P, Boulanger MC, Despres JP. Ectopic visceral fat: a clinical and molecular perspective on the cardiometabolic risk. Rev Endocr Metab Disord (2014) 15:289-98. doi:10.1007/s11154-014-9299-3
79. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol (2010) 316:129-39. doi:10.1016/j.mce.2009.08.018
80. Hocking SL, Wu LE, Guilhaus M, Chisholm DJ, James DE. Intrinsic depot-specific differences in the secretome of adipose tissue, preadipocytes, and adipose tissue-derived microvascular endothelial cells. Diabetes (2010) 59:3008-16. doi:10.2337/db10-0483
81. Van Harmelen V, Reynisdottir S, Eriksson P, Thorne A, Hoffstedt J, Lonnqvist F, et al. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes (1998) 47:913-7. doi:10.2337/diabetes.47.6.913
82. Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev (2000) 21:697-738. doi:10.1210/edrv.21.6.0415
83. Lihn AS, Bruun JM, He G, Pedersen SB, Jensen PF, Richelsen B. Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects. Mol Cell Endocrinol (2004) 219:9-15. doi:10.1016/j.mce.2004.03.002
84. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab (2001) 86:1930-5. doi:10.1210/jcem.86.5.7463
85. Cote M, Mauriege P, Bergeron J, Almeras N, Tremblay A, Lemieux I, et al. Adiponectinemia in visceral obesity: impact on glucose tolerance and plasma lipoprotein and lipid levels in men. J Clin Endocrinol Metab (2005) 90:1434-9. doi:10.1210/jc.2004-1711
86. Forouhi NG, Sattar N, Mckeigue PM. Relation of C-reactive protein to body fat distribution and features of the metabolic syndrome in Europeans and South Asians. Int J Obes Relat Metab Disord (2001) 25:1327-31. doi:10.1038/sj.ijo.0801723
87. Pou KM, Massaro JM, Hoffmann U, Vasan RS, Maurovich-Horvat P, Larson MG, et al. Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress-the Framingham heart study. Circulation (2007) 116:1234-41. doi:10.1161/CIRCULATIONAHA.107.710509
88. Bruun JM, Lihn AS, Pedersen SB, Richelsen B. Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT. J Clin Endocrinol Metab (2005) 90:2282-9. doi:10.1210/jc.2004-1696
89. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest (2005) 115:1111-9. doi:10.1172/JCI25102
90. Asterholm IW, Tao C, Morley TS, Wang QA, Delgado-Lopez F, Wang ZV, et al. Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling. Cell Metab (2014) 20:103-18. doi:10.1016/j.cmet.2014.05.005
91. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res (2005) 46:2347-55. doi:10.1194/jlr.M500294-JLR200
92. Strissel KJ, Stancheva Z, Miyoshi H, Perfield JW II, Defuria J, Jick Z, et al. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes (2007) 56:2910-8. doi:10.2337/db07-0767
93. Fried SK, Leibel RL, Edens NK, Kral JG. Lipolysis in intraabdominal adipose tissues of obese women and men. Obes Res (1993) 1:443-8. doi:10.1002/j.1550-8528.1993.tb00026.x
94. Lemieux S, Despres JP. Metabolic complications of visceral obesity contribution to the etiology of type-2 diabetes and implications for prevention and treatment. Diabete Metab (1994) 20:375-93.
95. Arner P. Differences in lipolysis between human subcutaneous and omental adipose tissues. Ann Med (1995) 27:435-8. doi:10.3109/07853899709002451
96. Fried SK, Tittelbach T, Blumenthal J, Sreenivasan U, Robey L, Yi J, et al. Resistance to the antilipolytic effect of insulin in adipocytes of African-American compared to Caucasian postmenopausal women. J Lipid Res (2010) 51:1193-200. doi:10.1194/jlr.P000935
97. Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev (2010) 11:11-8. doi:10.1111/j.1467-789X.2009.00623.x
98. Bjorntorp P. Portal adipose-tissue as a generator of risk-factors for cardiovascular-disease and diabetes. Arteriosclerosis (1990) 10:493-6. doi:10.1161/01.ATV.10.4.493
99. Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes (1997) 46:3-10. doi:10.2337/diab.46.1.3
100. Seppala-Lindroos A, Vehkavaara S, Hakkinen AM, Goto T, Westerbacka J, Sovijarvi A, et al. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab (2002) 87:3023-8. doi:10.1210/jcem.87.7.8638
101. Virkamaki A, Korsheninnikova E, Seppala-Lindroos A, Vehkavaara S, Goto T, Halavaara J, et al. Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle. Diabetes (2001) 50:2337-43. doi:10.2337/diabetes.50.10.2337
102. Klein S. The case of visceral fat: argument for the defense. J Clin Invest (2004) 113:1530-2. doi:10.1172/JCI200422028
103. Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD. Splanchnic lipolysis in human obesity. J Clin Invest (2004) 113:1582-8. doi:10.1172/JCI21047
104. Huang-Doran I, Sleigh A, Rochford JJ, O'Rahilly S, Savage DB. Lipodystrophy: metabolic insights from a rare disorder. J Endocrinol (2010) 207:245-55. doi:10.1677/JOE-10-0272
105. Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet (1999) 353:2093-9. doi:10.1016/S0140-6736(98)08468-2
106. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev (2005) 26:439-51. doi:10.1210/er.2005-0005
107. Van De Vyver M, Andrag E, Cockburn IL, Ferris WF. Thiazolidinedione-induced lipid droplet formation during osteogenic differentiation. J Endocrinol (2014) 223:119-32. doi:10.1530/JOE-14-0425
108. Klein S, Fontana L, Young VL, Coggan AR, Kilo C, Patterson BW, et al. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med (2004) 350:2549-57. doi:10.1056/NEJMoa033179
109. Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW, Berg AH, et al. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? Diabetes (2002) 51:2951-8. doi:10.2337/diabetes.51.10.2951
110. Klein S. Is visceral fat responsible for the metabolic abnormalities associated with obesity?: implications of omentectomy. Diabetes Care (2010) 33:1693-4. doi:10.2337/dc10-0744
111. Molero JC, Turner N, Thien CB, Langdon WY, James DE, Cooney GJ. Genetic ablation of the c-Cbl ubiquitin ligase domain results in increased energy expenditure and improved insulin action. Diabetes (2006) 55:3411-7. doi:10.2337/db06-0955
112. Kim DH, Sartor MA, Bain JR, Sandoval D, Stevens RD, Medvedovic M, et al. Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium. Diabetes (2012) 61:2299-310. doi:10.2337/db11-1579
113. Lemoine AY, Ledoux S, Larger E. Adipose tissue angiogenesis in obesity. Thromb Haemost (2013) 110:661-8. doi:10.1160/TH13-01-0073
114. Gesta S, Tseng YH, Kahn CR. Developmental origin of fat: tracking obesity to its source. Cell (2007) 131:242-56. doi:10.1016/j.cell.2007.10.004
115. Lee KY, Yamamoto Y, Boucher J, Winnay JN, Gesta S, Cobb J, et al. Shox2 is a molecular determinant of depot-specific adipocyte function. Proc Natl Acad Sci U S A (2013) 110:11409-14. doi:10.1073/pnas.1310331110
116. Van Der Lans AA, Hoeks J, Brans B, Vijgen GH, Visser MG, Vosselman MJ, et al. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J Clin Invest (2013) 123:3395-403. doi:10.1172/JCI68993
117. Yoneshiro T, Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y, et al. Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest (2013) 123:3404-8. doi:10.1172/JCI67803
118. Lee P, Smith S, Linderman J, Courville AB, Brychta RJ, Dieckmann W, et al. Temperature-acclimated brown adipose tissue modulates insulin sensitivity in humans. Diabetes (2014) 63:3686-98. doi:10.2337/db14-0513
119. Redman LM, De Jonge L, Fang X, Gamlin B, Recker D, Greenway FL, et al. Lack of an effect of a novel beta3-adrenoceptor agonist, TAK-677, on energy metabolism in obese individuals: a double-blind, placebo-controlled randomized study. J Clin Endocrinol Metab (2007) 92:527-31. doi:10.1210/jc.2006-1740
120. Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab (2014) 19:302-9. doi:10.1016/j.cmet.2013.12.017