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Adipose Structure (White, Brown, Beige)

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Metabolic Syndrome

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Abstract

Our understanding of adipose tissue physiology and pathophysiology has substantially increased during the last decade. Notably, white adipose tissue (WAT) dysfunction has been proposed as a critical determinant of obesity-associated metabolic complications. WAT is a complex metabolic organ composed of many cell types, including adipocytes, the primary cell type involved in energy storage. Adipocytes also synthesize numerous molecules that regulate energy balance, vascular homeostasis, and insulin sensitivity. In obesity, WAT expansion is associated with intensified structural remodeling that compromises the tissue’s metabolic and secretory functions. Failure to efficiently store lipids in WAT results in a “spillover” of the excess lipids into non-adipose tissues, which further disrupts metabolic homeostasis and contributes to the development of obesity-related pathologies, known collectively as metabolic syndrome.

In contrast, brown adipose tissue (BAT) is an energy-dissipating thermogenic organ that produces heat by uncoupling mitochondrial fatty acid oxidation. Activation of BAT thermogenesis can ameliorate the effects of WAT dysfunction in metabolically compromised mouse models. The rediscovery of BAT in humans has raised the possibility that BAT could be a therapeutic target for metabolic syndrome. This chapter will discuss important structural and cellular features of the WAT and BAT and how obesity alters WAT and BAT structure, intercellular crosstalk, and function.

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References

  1. Alcala M, Calderon-Dominguez M, Serra D, Herrero L, Viana M. Mechanisms of impaired brown adipose tissue recruitment in obesity. Front Physiol. 2019;10:94. https://doi.org/10.3389/fphys.2019.00094.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Andreozzi F, Laratta E, Procopio C, Hribal ML, Sciacqua A, Perticone M, … Sesti G. Interleukin-6 impairs the insulin signaling pathway, promoting production of nitric oxide in human umbilical vein endothelial cells. Mol Cell Biol. 2007;27(6):2372–83. https://doi.org/10.1128/MCB.01340-06.

  3. Angueira AR, Sakers AP, Holman CD, Cheng L, Arbocco MN, Shamsi F, … Seale P. Defining the lineage of thermogenic perivascular adipose tissue. Nat Metab. 2021;3(4):469–84. https://doi.org/10.1038/s42255-021-00380-0.

  4. Antoniak K, Hansdorfer-Korzon R, Mrugacz M, Zorena K. Adipose tissue and biological factors. Possible link between lymphatic system dysfunction and obesity. Metabolites. 2021;11(9):617. https://doi.org/10.3390/metabo11090617.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bagchi M, Kim LA, Boucher J, Walshe TE, Kahn CR, D’Amore PA. Vascular endothelial growth factor is important for brown adipose tissue development and maintenance. FASEB J. 2013;27(8):3257–71. https://doi.org/10.1096/fj.12-221812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, … Heeren J. Brown adipose tissue activity controls triglyceride clearance. Nat Med. 2011;17(2):200–5. https://doi.org/10.1038/nm.2297.

  7. Bjorndal B, Burri L, Staalesen V, Skorve J, Berge RK. Different adipose depots: their role in the development of metabolic syndrome and mitochondrial response to hypolipidemic agents. J Obes. 2011;2011:490650. https://doi.org/10.1155/2011/490650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Blaszkiewicz M, Wood E, Koizar S, Willows J, Anderson R, Tseng YH, … Townsend KL. The involvement of neuroimmune cells in adipose innervation. Mol Med. 2020;26(1):126. https://doi.org/10.1186/s10020-020-00254-3.

  9. Bordicchia M, Liu D, Amri EZ, Ailhaud G, Dessi-Fulgheri P, Zhang C, … Collins S. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest. 2012;122(3):1022–36. https://doi.org/10.1172/JCI59701.

  10. Boren J, Taskinen MR, Olofsson SO, Levin M. Ectopic lipid storage and insulin resistance: a harmful relationship. J Intern Med. 2013;274(1):25–40. https://doi.org/10.1111/joim.12071.

    Article  CAS  PubMed  Google Scholar 

  11. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, … Spiegelman BM. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463–8. https://doi.org/10.1038/nature10777.

  12. Brakenhielm E, Veitonmaki N, Cao R, Kihara S, Matsuzawa Y, Zhivotovsky B, … Cao Y. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A. 2004;101(8):2476–81. https://doi.org/10.1073/pnas.0308671100.

  13. Brito NA, Brito MN, Bartness TJ. Differential sympathetic drive to adipose tissues after food deprivation, cold exposure or glucoprivation. Am J Physiol Regul Integr Comp Physiol. 2008;294(5):R1445–52. https://doi.org/10.1152/ajpregu.00068.2008.

    Article  CAS  PubMed  Google Scholar 

  14. Campderros L, Moure R, Cairo M, Gavalda-Navarro A, Quesada-Lopez T, Cereijo R, … Villarroya F. Brown adipocytes secrete GDF15 in response to thermogenic activation. Obesity (Silver Spring). 2019;27(10):1606–16. https://doi.org/10.1002/oby.22584.

  15. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84(1):277–359. https://doi.org/10.1152/physrev.00015.2003.

    Article  CAS  PubMed  Google Scholar 

  16. Cannon B, Nedergaard J. Nonshivering thermogenesis and its adequate measurement in metabolic studies. J Exp Biol. 2011;214(Pt 2):242–53. https://doi.org/10.1242/jeb.050989.

    Article  PubMed  Google Scholar 

  17. Cao R, Brakenhielm E, Wahlestedt C, Thyberg J, Cao Y. Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. Proc Natl Acad Sci U S A. 2001;98(11):6390–5. https://doi.org/10.1073/pnas.101564798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Carobbio S, Rosen B, Vidal-Puig A. Adipogenesis: new insights into brown adipose tissue differentiation. J Mol Endocrinol. 2013;51(3):T75–85. https://doi.org/10.1530/JME-13-0158.

    Article  CAS  PubMed  Google Scholar 

  19. Cereijo R, Gavalda-Navarro A, Cairo M, Quesada-Lopez T, Villarroya J, Moron-Ros S, … Villarroya F. CXCL14, a brown adipokine that mediates brown-fat-to-macrophage communication in thermogenic adaptation. Cell Metab. 2018;28(5):750–763.e6. https://doi.org/10.1016/j.cmet.2018.07.015.

  20. Cero C, Lea HJ, Zhu KY, Shamsi F, Tseng YH, Cypess AM. beta3-adrenergic receptors regulate human brown/beige adipocyte lipolysis and thermogenesis. Insight. 2021;6(11):e139160. https://doi.org/10.1172/jci.insight.139160.

    Article  Google Scholar 

  21. Chan M, Lim YC, Yang J, Namwanje M, Liu L, Qiang L. Identification of a natural beige adipose depot in mice. J Biol Chem. 2019;294(17):6751–61. https://doi.org/10.1074/jbc.RA118.006838.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chen SX, Zhang LJ, Gallo RL. Dermal white adipose tissue: a newly recognized layer of skin innate defense. J Invest Dermatol. 2019;139(5):1002–9. https://doi.org/10.1016/j.jid.2018.12.031.

    Article  CAS  PubMed  Google Scholar 

  23. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, … Obin MS. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46(11):2347–55. https://doi.org/10.1194/jlr.M500294-JLR200.

  24. Coppack SW. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc. 2001;60(3):349–56. https://doi.org/10.1079/pns2001110.

    Article  CAS  PubMed  Google Scholar 

  25. Cottam MA, Caslin HL, Winn NC, Hasty AH. Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice. Nat Commun. 2022;13(1):2950. https://doi.org/10.1038/s41467-022-30646-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Craft CS, Pietka TA, Schappe T, Coleman T, Combs MD, Klein S, … Mecham RP. The extracellular matrix protein MAGP1 supports thermogenesis and protects against obesity and diabetes through regulation of TGF-beta. Diabetes. 2014;63(6):1920–32. https://doi.org/10.2337/db13-1604.

  27. Deutsch A, Feng D, Pessin JE, Shinoda K. The impact of single-cell genomics on adipose tissue research. Int J Mol Sci. 2020;21(13):4773. https://doi.org/10.3390/ijms21134773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Divoux A, Tordjman J, Lacasa D, Veyrie N, Hugol D, Aissat A, … Clement K. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes. 2010;59(11):2817–25. https://doi.org/10.2337/db10-0585.

  29. Duffaut C, Galitzky J, Lafontan M, Bouloumie A. Unexpected trafficking of immune cells within the adipose tissue during the onset of obesity. Biochem Biophys Res Commun. 2009;384(4):482–5. https://doi.org/10.1016/j.bbrc.2009.05.002.

    Article  CAS  PubMed  Google Scholar 

  30. Elias I, Franckhauser S, Bosch F. New insights into adipose tissue VEGF-A actions in the control of obesity and insulin resistance. Adipocytes. 2013;2(2):109–12. https://doi.org/10.4161/adip.22880.

    Article  CAS  Google Scholar 

  31. Emont MP, Jacobs C, Essene AL, Pant D, Tenen D, Colleluori G, … Rosen ED. A single-cell atlas of human and mouse white adipose tissue. Nature. 2022;603(7903):926–33. https://doi.org/10.1038/s41586-022-04518-2.

  32. Feldmann HM, Golozoubova V, Cannon B, Nedergaard J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 2009;9(2):203–9. https://doi.org/10.1016/j.cmet.2008.12.014.

    Article  CAS  PubMed  Google Scholar 

  33. Felix I, Jokela H, Karhula J, Kotaja N, Savontaus E, Salmi M, Rantakari P. Single-cell proteomics reveals the defined heterogeneity of resident macrophages in white adipose tissue. Front Immunol. 2021;12:719979. https://doi.org/10.3389/fimmu.2021.719979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Fischer K, Ruiz HH, Jhun K, Finan B, Oberlin DJ, van der Heide V, … Buettner C. Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis. Nat Med. 2017;23(5):623–30. https://doi.org/10.1038/nm.4316.

  35. Fu L, John LM, Adams SH, Yu XX, Tomlinson E, Renz M, … Stewart TA. Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes. Endocrinology. 2004;145(6):2594–603. https://doi.org/10.1210/en.2003-1671.

  36. Gealekman O, Guseva N, Hartigan C, Apotheker S, Gorgoglione M, Gurav K, … Corvera S. Depot-specific differences and insufficient subcutaneous adipose tissue angiogenesis in human obesity. Circulation. 2011;123(2):186–94. https://doi.org/10.1161/CIRCULATIONAHA.110.970145.

  37. Giordano A, Morroni M, Santone G, Marchesi GF, Cinti S. Tyrosine hydroxylase, neuropeptide Y, substance P, calcitonin gene-related peptide and vasoactive intestinal peptide in nerves of rat periovarian adipose tissue: an immunohistochemical and ultrastructural investigation. J Neurocytol. 1996;25(2):125–36. https://doi.org/10.1007/BF02284791.

    Article  CAS  PubMed  Google Scholar 

  38. Giorgino F, Laviola L, Eriksson JW. Regional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies. Acta Physiol Scand. 2005;183(1):13–30. https://doi.org/10.1111/j.1365-201X.2004.01385.x.

    Article  CAS  PubMed  Google Scholar 

  39. Gonzalez Porras MA, Stojkova K, Vaicik MK, Pelowe A, Goddi A, Carmona A, … Brey EM. Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity. Sci Rep. 2021;11(1):5442. https://doi.org/10.1038/s41598-021-84828-z.

  40. Hanssen MJ, van der Lans AA, Brans B, Hoeks J, Jardon KM, Schaart G, … van Marken Lichtenbelt WD. Short-term cold acclimation recruits brown adipose tissue in obese humans. Diabetes. 2016;65(5):1179–89. https://doi.org/10.2337/db15-1372.

  41. Haraida S, Nerlich AG, Wiest I, Schleicher E, Lohrs U. Distribution of basement membrane components in normal adipose tissue and in benign and malignant tumors of lipomatous origin. Mod Pathol. 1996;9(2):137–44.

    CAS  PubMed  Google Scholar 

  42. Henegar C, Tordjman J, Achard V, Lacasa D, Cremer I, Guerre-Millo M, … Clement, K. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol. 2008;9(1):R14. https://doi.org/10.1186/gb-2008-9-1-r14.

  43. Henriques F, Bedard AH, Guilherme A, Kelly M, Chi J, Zhang P, … Czech MP. Single-cell RNA profiling reveals adipocyte to macrophage signaling sufficient to enhance thermogenesis. Cell Rep. 2020;32(5):107998. https://doi.org/10.1016/j.celrep.2020.107998.

  44. Himms-Hagen J, Cui J, Danforth E Jr, Taatjes DJ, Lang SS, Waters BL, Claus TH. Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. Am J Phys. 1994;266(4 Pt 2):R1371–82. https://doi.org/10.1152/ajpregu.1994.266.4.R1371.

    Article  CAS  Google Scholar 

  45. Holland J, Sorrell J, Yates E, Smith K, Arbabi S, Arnold M, … Perez-Tilve D. A brain-melanocortin-vagus axis mediates adipose tissue expansion independently of energy intake. Cell Rep. 2019;27(8):2399–410. e2396. https://doi.org/10.1016/j.celrep.2019.04.089.

  46. Hondares E, Iglesias R, Giralt A, Gonzalez FJ, Giralt M, Mampel T, Villarroya F. Thermogenic activation induces FGF21 expression and release in brown adipose tissue. J Biol Chem. 2011;286(15):12983–90. https://doi.org/10.1074/jbc.M110.215889.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hondares E, Gallego-Escuredo JM, Flachs P, Frontini A, Cereijo R, Goday A, … Villarroya F. Fibroblast growth factor-21 is expressed in neonatal and pheochromocytoma-induced adult human brown adipose tissue. Metabolism. 2014;63(3):312–7. https://doi.org/10.1016/j.metabol.2013.11.014.

  48. Hong S, Song W, Zushin PH, Liu B, Jedrychowski MP, Mina AI, … Banks AS. Phosphorylation of Beta-3 adrenergic receptor at serine 247 by ERK MAP kinase drives lipolysis in obese adipocytes. Mol Metab. 2018;12:25–38. https://doi.org/10.1016/j.molmet.2018.03.012.

  49. Hu P, Luo BH. Integrin bi-directional signaling across the plasma membrane. J Cell Physiol. 2013;228(2):306–12. https://doi.org/10.1002/jcp.24154.

    Article  CAS  PubMed  Google Scholar 

  50. Huang LO, Rauch A, Mazzaferro E, Preuss M, Carobbio S, Bayrak CS, … Loos RJF. Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities. Nat Metab. 2021;3(2):228–43. https://doi.org/10.1038/s42255-021-00346-2.

  51. Hunyenyiwa T, Hendee K, Matus K, Kyi P, Mammoto T, Mammoto A. Obesity inhibits angiogenesis through TWIST1-SLIT2 signaling. Front Cell Dev Biol. 2021;9:693410. https://doi.org/10.3389/fcell.2021.693410.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Ikeda K, Yamada T. UCP1 dependent and independent thermogenesis in Brown and Beige adipocytes. Front Endocrinol (Lausanne). 2020;11:498. https://doi.org/10.3389/fendo.2020.00498.

    Article  PubMed  Google Scholar 

  53. Isakson P, Hammarstedt A, Gustafson B, Smith U. Impaired preadipocyte differentiation in human abdominal obesity: role of Wnt, tumor necrosis factor-alpha, and inflammation. Diabetes. 2009;58(7):1550–7. https://doi.org/10.2337/db08-1770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Jaitin DA, Adlung L, Thaiss CA, Weiner A, Li B, Descamps H, … Amit, I.. Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner. Cell. 2019;178(3):686–698.e14. https://doi.org/10.1016/j.cell.2019.05.054.

  55. Janssen I, Powell LH, Kazlauskaite R, Dugan SA. Testosterone and visceral fat in midlife women: the Study of Women’s Health Across the Nation (SWAN) fat patterning study. Obesity (Silver Spring). 2010;18(3):604–10. https://doi.org/10.1038/oby.2009.251.

    Article  CAS  PubMed  Google Scholar 

  56. Jespersen NZ, Feizi A, Andersen ES, Heywood S, Hattel HB, Daugaard S, … Scheele C. Heterogeneity in the perirenal region of humans suggests presence of dormant brown adipose tissue that contains brown fat precursor cells. Mol Metab. 2019;24:30–43. https://doi.org/10.1016/j.molmet.2019.03.005.

  57. Jumabay M, Zhang L, Yao J, Bostrom KI. Progenitor cells from brown adipose tissue undergo neurogenic differentiation. Sci Rep. 2022;12(1):5614. https://doi.org/10.1038/s41598-022-09382-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kimura H, Nagoshi T, Oi Y, Yoshii A, Tanaka Y, Takahashi H, … Yoshimura M. Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo. Sci Rep. 2021;11(1):17466. https://doi.org/10.1038/s41598-021-96970-9.

  59. Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M, … Marx, N.. T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol. 2008;28(7):1304–10. https://doi.org/10.1161/ATVBAHA.108.165100.

  60. Kobashi C, Urakaze M, Kishida M, Kibayashi E, Kobayashi H, Kihara S, … Kobayashi M. Adiponectin inhibits endothelial synthesis of interleukin-8. Circ Res. 2005;97(12):1245–52. https://doi.org/10.1161/01.RES.0000194328.57164.36.

  61. Kotzbeck P, Giordano A, Mondini E, Murano I, Severi I, Venema W, … Cinti S. Brown adipose tissue whitening leads to brown adipocyte death and adipose tissue inflammation. J Lipid Res. 2018;59(5):784–94. https://doi.org/10.1194/jlr.M079665.

  62. Kratz M, Coats BR, Hisert KB, Hagman D, Mutskov V, Peris E, … Becker L. Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab. 2014;20(4):614–25. https://doi.org/10.1016/j.cmet.2014.08.010.

  63. Kulterer OC, Herz CT, Prager M, Schmoltzer C, Langer FB, Prager G, … Kiefer FW. Brown adipose tissue prevalence is lower in obesity but its metabolic activity is intact. Front Endocrinol (Lausanne). 2022;13:858417. https://doi.org/10.3389/fendo.2022.858417.

  64. Kunduzova O, Alet N, Delesque-Touchard N, Millet L, Castan-Laurell I, Muller C, … Valet P. Apelin/APJ signaling system: a potential link between adipose tissue and endothelial angiogenic processes. FASEB J. 2008;22(12):4146–53. https://doi.org/10.1096/fj.07-104018.

  65. Lean ME. Brown adipose tissue in humans. Proc Nutr Soc. 1989;48(2):243–56. https://doi.org/10.1079/pns19890036.

    Article  CAS  PubMed  Google Scholar 

  66. LeBleu VS, Macdonald B, Kalluri R. Structure and function of basement membranes. Exp Biol Med (Maywood). 2007;232(9):1121–9. https://doi.org/10.3181/0703-MR-72.

    Article  CAS  PubMed  Google Scholar 

  67. Lee P, Greenfield JR, Ho KK, Fulham MJ. A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2010;299(4):E601–6. https://doi.org/10.1152/ajpendo.00298.2010.

    Article  CAS  PubMed  Google Scholar 

  68. Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, … Celi FS. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab. 2014;19(2):302–9. https://doi.org/10.1016/j.cmet.2013.12.017.

  69. Lee KY, Luong Q, Sharma R, Dreyfuss JM, Ussar S, Kahn CR. Developmental and functional heterogeneity of white adipocytes within a single fat depot. EMBO J. 2019;38(3):e99291. https://doi.org/10.15252/embj.201899291.

    Article  CAS  PubMed  Google Scholar 

  70. Li H, Konja D, Wang L, Wang Y. Sex differences in adiposity and cardiovascular diseases. Int J Mol Sci. 2022;23(16):9338. https://doi.org/10.3390/ijms23169338.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Lidell ME, Betz MJ, Dahlqvist Leinhard O, Heglind M, Elander L, Slawik M, … Enerback S. Evidence for two types of brown adipose tissue in humans. Nat Med. 2013;19(5):631–4. https://doi.org/10.1038/nm.3017.

  72. Liu X, Perusse F, Bukowiecki LJ. Mechanisms of the antidiabetic effects of the beta 3-adrenergic agonist CL-316243 in obese Zucker-ZDF rats. Am J Phys. 1998;274(5):R1212–9. https://doi.org/10.1152/ajpregu.1998.274.5.R1212.

    Article  CAS  Google Scholar 

  73. Lopez M, Alvarez CV, Nogueiras R, Dieguez C. Energy balance regulation by thyroid hormones at central level. Trends Mol Med. 2013;19(7):418–27. https://doi.org/10.1016/j.molmed.2013.04.004.

    Article  CAS  PubMed  Google Scholar 

  74. Love-Gregory L, Abumrad NA. CD36 genetics and the metabolic complications of obesity. Curr Opin Clin Nutr Metab Care. 2011;14(6):527–34. https://doi.org/10.1097/MCO.0b013e32834bbac9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117(1):175–84. https://doi.org/10.1172/JCI29881.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Lundgren M, Svensson M, Lindmark S, Renstrom F, Ruge T, Eriksson JW. Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’. Diabetologia. 2007;50(3):625–33. https://doi.org/10.1007/s00125-006-0572-1.

    Article  CAS  PubMed  Google Scholar 

  77. Mariman EC, Wang P. Adipocyte extracellular matrix composition, dynamics and role in obesity. Cell Mol Life Sci. 2010;67(8):1277–92. https://doi.org/10.1007/s00018-010-0263-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Mesa AM, Medrano TI, Sirohi VK, Walker WH, Johnson RD, Tevosian SG, … Cooke PS. Identification and characterization of novel abdominal and pelvic brown adipose depots in mice. Adipocytes. 2022;11(1):616–29. https://doi.org/10.1080/21623945.2022.2133415.

  79. Miller NE, Michel CC, Nanjee MN, Olszewski WL, Miller IP, Hazell M, … Frayn KN. Secretion of adipokines by human adipose tissue in vivo: partitioning between capillary and lymphatic transport. Am J Physiol Endocrinol Metab. 2011;301(4):E659–67. https://doi.org/10.1152/ajpendo.00058.2011.

  80. Mori S, Kiuchi S, Ouchi A, Hase T, Murase T. Characteristic expression of extracellular matrix in subcutaneous adipose tissue development and adipogenesis; comparison with visceral adipose tissue. Int J Biol Sci. 2014;10(8):825–33. https://doi.org/10.7150/ijbs.8672.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Mur C, Valverde AM, Kahn CR, Benito M. Increased insulin sensitivity in IGF-I receptor – deficient brown adipocytes. Diabetes. 2002;51(3):743–54. https://doi.org/10.2337/diabetes.51.3.743.

    Article  CAS  PubMed  Google Scholar 

  82. Murano I, Barbatelli G, Giordano A, Cinti S. Noradrenergic parenchymal nerve fiber branching after cold acclimatisation correlates with brown adipocyte density in mouse adipose organ. J Anat. 2009;214(1):171–8. https://doi.org/10.1111/j.1469-7580.2008.01001.x.

    Article  CAS  PubMed  Google Scholar 

  83. Muzik O, Mangner TJ, Leonard WR, Kumar A, Janisse J, Granneman JG. 15O PET measurement of blood flow and oxygen consumption in cold-activated human brown fat. J Nucl Med. 2013;54(4):523–31. https://doi.org/10.2967/jnumed.112.111336.

    Article  CAS  PubMed  Google Scholar 

  84. Nguyen KD, Qiu Y, Cui X, Goh YP, Mwangi J, David T, … Chawla A. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature. 2011;480(7375):104–8. https://doi.org/10.1038/nature10653.

  85. Nijhuis J, Rensen SS, Slaats Y, van Dielen FM, Buurman WA, Greve JW. Neutrophil activation in morbid obesity, chronic activation of acute inflammation. Obesity (Silver Spring). 2009;17(11):2014–8. https://doi.org/10.1038/oby.2009.113.

    Article  CAS  PubMed  Google Scholar 

  86. Orava J, Nuutila P, Noponen T, Parkkola R, Viljanen T, Enerback S, … Virtanen KA. Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans. Obesity (Silver Spring). 2013;21(11):2279–87. https://doi.org/10.1002/oby.20456.

  87. Ouchi N, Kobayashi H, Kihara S, Kumada M, Sato K, Inoue T, … Walsh K. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem. 2004;279(2):1304–9. https://doi.org/10.1074/jbc.M310389200.

  88. Ouellet V, Routhier-Labadie A, Bellemare W, Lakhal-Chaieb L, Turcotte E, Carpentier AC, Richard D. Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. J Clin Endocrinol Metab. 2011;96(1):192–9. https://doi.org/10.1210/jc.2010-0989.

    Article  CAS  PubMed  Google Scholar 

  89. Peeraully MR, Jenkins JR, Trayhurn P. NGF gene expression and secretion in white adipose tissue: regulation in 3T3-L1 adipocytes by hormones and inflammatory cytokines. Am J Physiol Endocrinol Metab. 2004;287(2):E331–9. https://doi.org/10.1152/ajpendo.00076.2004.

    Article  CAS  PubMed  Google Scholar 

  90. Pellegrinelli V, Heuvingh J, du Roure O, Rouault C, Devulder A, Klein C, … Clement K. Human adipocyte function is impacted by mechanical cues. J Pathol. 2014;233(2):183–95. https://doi.org/10.1002/path.4347.

  91. Pellegrinelli V, Rouault C, Veyrie N, Clement K, Lacasa D. Endothelial cells from visceral adipose tissue disrupt adipocyte functions in a three-dimensional setting: partial rescue by angiopoietin-1. Diabetes. 2014;63(2):535–49. https://doi.org/10.2337/db13-0537.

    Article  CAS  PubMed  Google Scholar 

  92. Pellegrinelli V, Rodriguez-Cuenca S, Rouault C, Figueroa-Juarez E, Schilbert H, Virtue S, … Vidal-Puig A. Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance. Nat Metab. 2022;4(4):476–94. https://doi.org/10.1038/s42255-022-00561-5.

  93. Potenza MA, Addabbo F, Montagnani M. Vascular actions of insulin with implications for endothelial dysfunction. Am J Physiol Endocrinol Metab. 2009;297(3):E568–77. https://doi.org/10.1152/ajpendo.00297.2009.

    Article  CAS  PubMed  Google Scholar 

  94. Purkayastha S, Cai D. Neuroinflammatory basis of metabolic syndrome. Mol Metab. 2013;2(4):356–63. https://doi.org/10.1016/j.molmet.2013.09.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Qiu Y, Nguyen KD, Odegaard JI, Cui X, Tian X, Locksley RM, … Chawla, A.. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell. 2014;157(6):1292–308. https://doi.org/10.1016/j.cell.2014.03.066.

  96. Rabelo R, Reyes C, Schifman A, Silva JE. Interactions among receptors, thyroid hormone response elements, and ligands in the regulation of the rat uncoupling protein gene expression by thyroid hormone. Endocrinology. 1996;137(8):3478–87. https://doi.org/10.1210/endo.137.8.8754777.

    Article  CAS  PubMed  Google Scholar 

  97. Rahman MS, Jun H. The adipose tissue macrophages central to adaptive thermoregulation. Front Immunol. 2022;13:884126. https://doi.org/10.3389/fimmu.2022.884126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Rao RR, Long JZ, White JP, Svensson KJ, Lou J, Lokurkar I, … Spiegelman BM. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell. 2014;157(6):1279–91. https://doi.org/10.1016/j.cell.2014.03.065.

  99. Roberts LD, Ashmore T, Kotwica AO, Murfitt SA, Fernandez BO, Feelisch M, … Griffin JL. Inorganic nitrate promotes the browning of white adipose tissue through the nitrate-nitrite-nitric oxide pathway. Diabetes. 2015;64(2):471–84. https://doi.org/10.2337/db14-0496.

  100. Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol. 2006;7(12):885–96. https://doi.org/10.1038/nrm2066.

    Article  CAS  PubMed  Google Scholar 

  101. Rosenwald M, Perdikari A, Rulicke T, Wolfrum C. Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol. 2013;15(6):659–67. https://doi.org/10.1038/ncb2740.

    Article  CAS  PubMed  Google Scholar 

  102. Rosina M, Ceci V, Turchi R, Chuan L, Borcherding N, Sciarretta F, … Lettieri-Barbato D. Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue. Cell Metab. 2022;34(4):533–548.e12. https://doi.org/10.1016/j.cmet.2022.02.016.

  103. Rouault C, Pellegrinelli V, Schilch R, Cotillard A, Poitou C, Tordjman J, … Lacasa D. Roles of chemokine ligand-2 (CXCL2) and neutrophils in influencing endothelial cell function and inflammation of human adipose tissue. Endocrinology. 2013;154(3):1069–79. https://doi.org/10.1210/en.2012-1415.

  104. Ryu V, Garretson JT, Liu Y, Vaughan CH, Bartness TJ. Brown adipose tissue has sympathetic-sensory feedback circuits. J Neurosci. 2015;35(5):2181–90. https://doi.org/10.1523/JNEUROSCI.3306-14.2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Saari TJ, Raiko J, U-Din M, Niemi T, Taittonen M, Laine J, … Virtanen KA. Basal and cold-induced fatty acid uptake of human brown adipose tissue is impaired in obesity. Sci Rep. 2020;10(1):14373. https://doi.org/10.1038/s41598-020-71197-2.

  106. Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, … Spiegelman BM. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008;454(7207):961–7. https://doi.org/10.1038/nature07182.

  107. Seale P, Conroe HM, Estall J, Kajimura S, Frontini A, Ishibashi J, … Spiegelman BM. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest. 2011;121(1):96–105. https://doi.org/10.1172/JCI44271.

  108. Shamsi F, Piper M, Ho LL, Huang TL, Gupta A, Streets A, … Tseng YH. Vascular smooth muscle-derived Trpv1(+) progenitors are a source of cold-induced thermogenic adipocytes. Nat Metab. 2021;3(4):485–95. https://doi.org/10.1038/s42255-021-00373-z.

  109. Shan B, Barker CS, Shao M, Zhang Q, Gupta RK, Wu Y. Multilayered omics reveal sex- and depot-dependent adipose progenitor cell heterogeneity. Cell Metab. 2022;34(5):783–799.e87. https://doi.org/10.1016/j.cmet.2022.03.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Shapira SN, Lim HW, Rajakumari S, Sakers AP, Ishibashi J, Harms MJ, … Seale, P.. EBF2 transcriptionally regulates brown adipogenesis via the histone reader DPF3 and the BAF chromatin remodeling complex. Genes Dev. 2017;31(7):660–73. https://doi.org/10.1101/gad.294405.116.

  111. Shimizu I, Aprahamian T, Kikuchi R, Shimizu A, Papanicolaou KN, MacLauchlan S, … Walsh K. Vascular rarefaction mediates whitening of brown fat in obesity. J Clin Invest. 2014;124(5):2099–112. https://doi.org/10.1172/JCI71643.

  112. Skarulis MC, Celi FS, Mueller E, Zemskova M, Malek R, Hugendubler L, … Gorden P. Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance. J Clin Endocrinol Metab. 2010;95(1):256–62. https://doi.org/10.1210/jc.2009-0543.

  113. Springer TA. Adhesion receptors of the immune system. Nature. 1990;346(6283):425–34. https://doi.org/10.1038/346425a0.

    Article  CAS  PubMed  Google Scholar 

  114. Strieder-Barboza C, Baker NA, Flesher CG, Karmakar M, Patel A, Lumeng CN, O’Rourke RW. Depot-specific adipocyte-extracellular matrix metabolic crosstalk in murine obesity. Adipocytes. 2020;9(1):189–96. https://doi.org/10.1080/21623945.2020.1749500.

    Article  CAS  Google Scholar 

  115. Strissel KJ, Stancheva Z, Miyoshi H, Perfield JW 2nd, DeFuria J, Jick Z, … Obin MS. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes. 2007;56(12):2910–8. https://doi.org/10.2337/db07-0767.

  116. Sun K, Park J, Gupta OT, Holland WL, Auerbach P, Zhang N, … Scherer PE. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction. Nat Commun. 2014;5:3485. https://doi.org/10.1038/ncomms4485.

  117. Sundberg C, Kowanetz M, Brown LF, Detmar M, Dvorak HF. Stable expression of angiopoietin-1 and other markers by cultured pericytes: phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of angiogenesis in vivo. Lab Investig. 2002;82(4):387–401. https://doi.org/10.1038/labinvest.3780433.

    Article  CAS  PubMed  Google Scholar 

  118. Tang QQ, Otto TC, Lane MD. Commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc Natl Acad Sci USA. 2004;101(26):9607–11. https://doi.org/10.1073/pnas.0403100101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Tchernof A, Belanger C, Morisset AS, Richard C, Mailloux J, Laberge P, Dupont P. Regional differences in adipose tissue metabolism in women: minor effect of obesity and body fat distribution. Diabetes. 2006;55(5):1353–60. https://doi.org/10.2337/db05-1439.

    Article  CAS  PubMed  Google Scholar 

  120. Tracy TF Jr. Editorial: acute pancreatitis and neutrophil gelatinase MMP9: don’t get me started! J Leukoc Biol. 2012;91(5):682–4. https://doi.org/10.1189/jlb.1111535.

    Article  CAS  PubMed  Google Scholar 

  121. Traktuev DO, Merfeld-Clauss S, Li J, Kolonin M, Arap W, Pasqualini R, … March KL. 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(1):77–85. https://doi.org/10.1161/CIRCRESAHA.107.159475.

  122. Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, … Kahn CR. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature. 2008;454(7207):1000–4. https://doi.org/10.1038/nature07221.

  123. Tupone D, Madden CJ, Morrison SF. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis. Front Neurosci. 2014;8:14. https://doi.org/10.3389/fnins.2014.00014.

    Article  PubMed  PubMed Central  Google Scholar 

  124. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, … Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360(15):1500–8. https://doi.org/10.1056/NEJMoa0808718.

  125. Vijay J, Gauthier MF, Biswell RL, Louiselle DA, Johnston JJ, Cheung WA, … Grundberg E. Single-cell analysis of human adipose tissue identifies depot and disease specific cell types. Nat Metab. 2020;2(1):97–109. https://doi.org/10.1038/s42255-019-0152-6.

  126. Villaret A, Galitzky J, Decaunes P, Esteve D, Marques MA, Sengenes C, … Bouloumie A. Adipose tissue endothelial cells from obese human subjects: differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence. Diabetes. 2010;59(11):2755–63. https://doi.org/10.2337/db10-0398.

  127. Vitali A, Murano I, Zingaretti MC, Frontini A, Ricquier D, Cinti S. The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes. J Lipid Res. 2012;53(4):619–29. https://doi.org/10.1194/jlr.M018846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Wang GX, Zhao XY, Meng ZX, Kern M, Dietrich A, Chen Z, … Lin JD. The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med. 2014;20(12):1436–43. https://doi.org/10.1038/nm.3713.

  129. Wang Q, Li D, Cao G, Shi Q, Zhu J, Zhang M, … Yin Z. IL-27 signalling promotes adipocyte thermogenesis and energy expenditure. Nature. 2021;600(7888):314–8. https://doi.org/10.1038/s41586-021-04127-5.

  130. Wang YN, Tang Y, He Z, Ma H, Wang L, Liu Y, … Tang QQ. Slit3 secreted from M2-like macrophages increases sympathetic activity and thermogenesis in adipose tissue. Nat Metab. 2021;3(11):1536–51. https://doi.org/10.1038/s42255-021-00482-9.

  131. Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, … Auwerx J. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439(7075):484–9. https://doi.org/10.1038/nature04330.

  132. Whittle AJ, Carobbio S, Martins L, Slawik M, Hondares E, Vazquez MJ, … Vidal-Puig A. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell. 2012;149(4):871–85. https://doi.org/10.1016/j.cell.2012.02.066.

  133. Xue Y, Petrovic N, Cao R, Larsson O, Lim S, Chen S, … Cao Y. Hypoxia-independent angiogenesis in adipose tissues during cold acclimation. Cell Metab. 2009;9(1):99–109. https://doi.org/10.1016/j.cmet.2008.11.009.

  134. Yadav RL, Sharma D, Yadav PK, Shah DK, Agrawal K, Khadka R, Islam MN. Somatic neural alterations in non-diabetic obesity: a cross-sectional study. BMC Obes. 2016;3:50. https://doi.org/10.1186/s40608-016-0131-3.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Yoneshiro T, Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y, … Saito M. Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest. 2013;123(8):3404–8. https://doi.org/10.1172/JCI67803.

  136. Zhang P, Wu S, He Y, Li X, Zhu Y, Lin X, … Shen L. LncRNA-mediated adipogenesis in different adipocytes. Int J Mol Sci. 2022;23(13). https://doi.org/10.3390/ijms23137488.

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  1. Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK

    Vanessa Pellegrinelli & Antonio Vidal-Puig

  2. Centro de Investigacion Principe Felipe, Valencia, Spain

    Antonio Vidal-Puig & Stefania Carobbio

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  1. Vanessa Pellegrinelli
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  2. Antonio Vidal-Puig
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  1. Division of Endocrinology, Diabetes and Metabolism Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA

    Rexford S. Ahima

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Pellegrinelli, V., Vidal-Puig, A., Carobbio, S. (2023). Adipose Structure (White, Brown, Beige). In: Ahima, R.S. (eds) Metabolic Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-031-40116-9_23

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