1932

Abstract

Rather than serving as a mere onlooker, adipose tissue is a complex endocrine organ and active participant in disease initiation and progression. Disruptions of biological processes operating within adipose can disturb healthy systemic physiology, the sequelae of which include metabolic disorders such as obesity and type 2 diabetes. A burgeoning interest in the field of adipose research has allowed for the elucidation of regulatory networks underlying both adipose tissue function and dysfunction. Despite this progress, few diseases are treated by targeting maladaptation in the adipose, an oft-overlooked organ. In this review, we elaborate on the distinct subtypes of adipocytes, their developmental origins and secretory roles, and the dynamic interplay at work within the tissue itself. Central to this discussion is the relationship between adipose and disease states, including obesity, cachexia, and infectious diseases, as we aim to leverage our wealth of knowledge for the development of novel and targeted therapeutics.

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2023-01-24
2024-05-14
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Literature Cited

  1. 1.
    Cook KS, Min HY, Johnson D, Chaplinsky RJ, Flier JS et al. 1987. Adipsin: a circulating serine protease homolog secreted by adipose tissue and sciatic nerve. Science 237:402–5
    [Google Scholar]
  2. 2.
    Cohen P, Kajimura S. 2021. The cellular and functional complexity of thermogenic fat. Nat. Rev. Mol. Cell Biol. 22:393
    [Google Scholar]
  3. 3.
    Corvera S. 2021. Cellular heterogeneity in adipose tissues. Annu. Rev. Physiol. 83:257–58
    [Google Scholar]
  4. 4.
    Ramirez AK, Dankel SN, Rastegarpanah B, Cai W, Xue R et al. 2020. Single-cell transcriptional networks in differentiating preadipocytes suggest drivers associated with tissue heterogeneity. Nat. Commun 11:1–9
    [Google Scholar]
  5. 5.
    Hildreth AD, Ma F, Wong YY, Sun R, Pellegrine M, O'Sullivan TE. 2021. Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity. Nat. Immunol. 22:639–53
    [Google Scholar]
  6. 6.
    Vijay J, Gauthier M, Biswell RL, Louiselle DA, Johnston JJ et al. 2020. Single-cell analysis of human adipose tissue identifies depot and disease specific cell types. Nat. Metab. 2:97–109
    [Google Scholar]
  7. 7.
    Chouchani ET, Kazak L, Spiegelman BM. 2019. New advances in adaptive thermogenesis: UCP1 and beyond. Cell Metab. 29:27–37
    [Google Scholar]
  8. 8.
    Sidossis L, Kajimura S. 2015. Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. J. Clin. Investig. 125:478–86
    [Google Scholar]
  9. 9.
    Hamdy O, Porramatikul S, Al-Ozairi E. 2006. Metabolic obesity: the paradox between visceral and subcutaneous fat. Curr. Diabetes Rev. 2:367–73
    [Google Scholar]
  10. 10.
    Finlin BS, Memetimin H, Zhu B, Confides AL, Vekaria HJ et al. 2020. The β3-adrenergic receptor agonist mirabegron improves glucose homeostasis in obese humans. J. Clin. Investig. 130:2319–31
    [Google Scholar]
  11. 11.
    O'Mara AE, Johnson JW, Linderman JD, Brychta RJ, McGehee S et al. 2020. Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity. J. Clin. Investig. 130:2209–19
    [Google Scholar]
  12. 12.
    Sveidahl Johansen O, Ma T, Hansen JB, Markussen LK, Schreiber R et al. 2021. Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis. Cell 184:3502–18
    [Google Scholar]
  13. 13.
    Chouchani ET, Kajimura S. 2019. Metabolic adaptation and maladaptation in adipose tissue. Nat. Metab. 1:189–200
    [Google Scholar]
  14. 14.
    Richard AJ, White U, Elks CM, Stephens JM. 2020. Adipose tissue: physiology to metabolic dysfunction. Endotext Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, et al South Dartmouth, MA: MDText.com, Inc https://www.ncbi.nlm.nih.gov/books/NBK555602/
    [Google Scholar]
  15. 15.
    Reilly SM, Saltiel AR. 2017. Adapting to obesity with adipose tissue inflammation. . Nat. Rev. Endocrinol. 13::633–43
    [Google Scholar]
  16. 16.
    Weinstock A, Silva HM, Moore KJ, Schmidt AM, Fisher EA. 2020. Leukocyte heterogeneity in adipose tissue, including in obesity. Circ. Res. 126:1590–612
    [Google Scholar]
  17. 17.
    Nawaz A, Aminuddin A, Kado T, Takikawa A, Yamamoto S et al. 2017. CD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors. Nat. Commun. 8:1–16
    [Google Scholar]
  18. 18.
    Liu C, Li P, Li H, Wang S, Ding L et al. 2019. TREM2 regulates obesity-induced insulin resistance via adipose tissue remodeling in mice of high-fat feeding. J. Transl. Med. 17:300
    [Google Scholar]
  19. 19.
    Deutsch A, Feng D, Pessin JE, Shinoda K. 2020. The impact of single-cell genomics on adipose tissue research. Int. J. Mol. Sci. 21:1–13
    [Google Scholar]
  20. 20.
    Merrick D, Sakers A, Irgebay Z, Okada C, Calvert C et al. 2019. Identification of a mesenchymal progenitor cell hierarchy in adipose tissue. Science 364:6438
    [Google Scholar]
  21. 21.
    Schwalie PC, Dong H, Zachara M, Russeil J, Alpern D et al. 2018. A stromal cell population that inhibits adipogenesis in mammalian fat depots. Nature 559:103–8
    [Google Scholar]
  22. 22.
    Shao M, Vishvanath L, Busbuso NC, Hepler C, Shan B et al. 2018. De novo adipocyte differentiation from PDGFRβ+ preadipocytes protects against pathologic visceral adipose expansion in obesity. Nat. Commun. 9:1–16
    [Google Scholar]
  23. 23.
    Gao Z, Daquinag AC, Su F, Snyder B, Kolonin MG. 2018. PDGFRα/PDGFRβ signaling balance modulates progenitor cell differentiation into white and beige adipocytes. Development 145:155861
    [Google Scholar]
  24. 24.
    Raajendiran A, Ooi G, Bayliss J, O'Brien PE, Schittenhelm RB et al. 2019. Identification of metabolically distinct adipocyte progenitor cells in human adipose tissues. Cell Rep. 27:1528–40
    [Google Scholar]
  25. 25.
    Bäckdahl J, Franzén L, Massier L, Li Q, Jalkanen J et al. 2021. Spatial mapping reveals human adipocyte subpopulations with distinct sensitivities to insulin. Cell Metab. 33:1869–82
    [Google Scholar]
  26. 26.
    Kajimura S, Spiegelman BM, Seale P. 2015. Brown and beige fat: physiological roles beyond heat generation. Cell Metab. 22:546–59
    [Google Scholar]
  27. 27.
    Wibmer AG, Becher T, Eljalby M, Crane A, Andrieu PC et al. 2021. Brown adipose tissue is associated with healthier body fat distribution and metabolic benefits independent of regional adiposity. Cell Rep. Med. 2:100332
    [Google Scholar]
  28. 28.
    Sebo ZL, Jeffery E, Holtrup B, Rodeheffer MS. 2018. A mesodermal fate map for adipose tissue. Development 145:166801
    [Google Scholar]
  29. 29.
    Sanchez-Gurmaches J, Guertin DA. 2014. Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nat. Commun. 5:4099
    [Google Scholar]
  30. 30.
    Seale P, Bjork B, Yang W, Kajimura S, Chin S et al. 2008. PRDM16 controls a brown fat/skeletal muscle switch. Nature 454:961–67
    [Google Scholar]
  31. 31.
    Lepper C, Fan C 2010. Inducible lineage tracing of Pax7-descendant cells reveals embryonic origin of adult satellite cells. Genesis 48:424–36
    [Google Scholar]
  32. 32.
    Shamsi F, Piper M, Ho L, Huang TL, Gupta A et al. 2021. Vascular smooth muscle-derived TRPV1-positive progenitors are a source of cold-induced thermogenic adipocytes. Nat. Metab. 3:485–95
    [Google Scholar]
  33. 33.
    Long JZ, Svensson KJ, Tsai L, Zeng X, Roh HC et al. 2014. A smooth muscle-like origin for beige adipocytes. Cell Metab. 19:810–20
    [Google Scholar]
  34. 34.
    Berry DC, Jiang Y, Graff JM. 2016. Mouse strains to study cold-inducible beige progenitors and beige adipocyte formation and function. Nat. Commun. 7:10184
    [Google Scholar]
  35. 35.
    Oguri Y, Shinoda K, Kim H, Alba DL, Bolus WR et al. 2020. CD81 controls beige fat progenitor cell growth and energy balance via FAK signaling. Cell 182:563–77
    [Google Scholar]
  36. 36.
    Altshuler-Keylin S, Shinoda K, Hasegawa Y, Ikeda K, Hong H et al. 2016. Beige adipocyte maintenance is regulated by autophagy-induced mitochondrial clearance. Cell Metab. 24:402–19
    [Google Scholar]
  37. 37.
    Lu X, Altshuler-Keylin S, Wang Q, Chen Y, Sponton CH et al. 2018. Mitophagy controls beige adipocyte maintenance through a Parkin-dependent and UCP1-independent mechanism. Sci. Signal. 11:527
    [Google Scholar]
  38. 38.
    Song A, Dai W, Jang MJ, Medrano L, Li Z et al. 2020. Low- and high-thermogenic brown adipocyte subpopulations coexist in murine adipose tissue. J. Clin. Investig. 130:247–57
    [Google Scholar]
  39. 39.
    Chen Y, Ikeda K, Yoneshiro T, Scaramozza A, Tajima K et al. 2019. Thermal stress induces glycolytic beige fat formation via a myogenic state. Nature 565:180–85
    [Google Scholar]
  40. 40.
    Sun W, Dong H, Balaz M, Slyper M, Drokhlyansky et al. 2020. snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesis. Nature 587:98–102
    [Google Scholar]
  41. 41.
    Crewe C, An YA, Scherer PE. 2017. The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. J. Clin. Investig. 127:74–82
    [Google Scholar]
  42. 42.
    Sun K, Tordjman J, Clément K, Scherer PE. 2013. Fibrosis and adipose tissue dysfunction. Cell Metab. 18:470–77
    [Google Scholar]
  43. 43.
    Khan T, Muise ES, Lyengar P, Wang ZV, Chandalia M et al. 2009. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol. Cell. Biol. 29:1575–91
    [Google Scholar]
  44. 44.
    Wang W, Ishibashi J, Trefely S, Shao M, Cowan AJ et al. 2019. A PRDM16-driven metabolic signal from adipocytes regulates precursor cell fate. Cell Metab. 30:174–89
    [Google Scholar]
  45. 45.
    Hasegawa Y, Ikeda K, Chen Y, Alba DL, Stifler D et al. 2018. Repression of adipose tissue fibrosis through a PRDM16-GTF2IRD1 complex improves systemic glucose homeostasis. Cell Metab. 27:180–94
    [Google Scholar]
  46. 46.
    Halberg N, Khan T, Trujillo ME, Wernstedt-Asterholm I, Attie AD et al. 2009. Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Mol. Cell. Biol. 29:4467–83
    [Google Scholar]
  47. 47.
    Spencer M, Yao-Borengasser A, Unal R, Rasouli N, Gurley CM et al. 2010. Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation. Am. J. Physiol. Endocrinol. Metab. 299:1016–27
    [Google Scholar]
  48. 48.
    Marcelin G, Ferreira A, Liu Y, Atlan M, Aron-Wisnewsky J et al. 2017. A PDGFRα-mediated switch toward CD9 high adipocyte progenitors controls obesity-induced adipose tissue fibrosis. Cell Metab. 25:673–85
    [Google Scholar]
  49. 49.
    Shao M, Hepler C, Zhang Q, Shan B, Vishvanath L et al. 2021. Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity. Cell Stem Cell 28:685–701
    [Google Scholar]
  50. 50.
    Sun K, Halberg N, Khan M, Magalang UJ, Scherer PE. 2013. Selective inhibition of hypoxia-inducible factor 1α ameliorates adipose tissue dysfunction. Mol. Cell. Biol. 33:904–17
    [Google Scholar]
  51. 51.
    Cao Y. 2010. Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases. Nat. Rev. Drug. Discov. 9:107–15
    [Google Scholar]
  52. 52.
    Herold J, Kalucka J. 2021. Angiogenesis in adipose tissue: the interplay between adipose and endothelial cells. Front. Physiol. 11:1861
    [Google Scholar]
  53. 53.
    Cao Y. 2007. Angiogenesis modulates adipogenesis and obesity. J. Clin. Investig. 117:2362–68
    [Google Scholar]
  54. 54.
    Yeh JR, Mohan R, Crews CM. 2000. The antiangiogenic agent TNP-470 requires p53 and p21CIP/WAF for endothelial cell growth arrest. PNAS 97:12782–87
    [Google Scholar]
  55. 55.
    Bråkenhielm E, Cao R, Gao B, Angelin B, Cannon B et al. 2004. Angiogenesis inhibitor, TNP-470, prevents diet induced and genetic obesity in mice. Circ. Res. 94:1579–88
    [Google Scholar]
  56. 56.
    Sun K, Kusminski CM, Luby-Phelps K, Spurgin SB, An YA et al. 2014. Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure. Mol. Metab. 3:474–83
    [Google Scholar]
  57. 57.
    Xue Y, Xu X, Zhang XQ, Farokhzad OC, Langer R. 2016. Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles. PNAS 113:5552–57
    [Google Scholar]
  58. 58.
    Abdullahi A, Knuth CM, Auger C, Sivayoganathan T, Parousis A, Jeschke MG. 2021. Adipose browning response to burn trauma is impaired with aging. JCI Insight 6:143451
    [Google Scholar]
  59. 59.
    Tchkonia T, Morbeck DE, Von Zglinicki T, Van Deursen J, Lustgarten J et al. 2010. Fat tissue, aging, and cellular senescence. Aging Cell 9:667–84
    [Google Scholar]
  60. 60.
    Campisi J. 2013. Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 75:685–705
    [Google Scholar]
  61. 61.
    Berry DC, Jiang Y, Arpke RW, Close EL, Uchida A et al. 2017. Cellular aging contributes to failure of cold-induced beige adipocyte formation in old mice and humans. Cell Metab. 25:166–81
    [Google Scholar]
  62. 62.
    Caso G, McNurlan MA, Mileva I, Zemlyak A, Mynarcik DC, Gelato MC. 2013. Peripheral fat loss and decline in adipogenesis in older humans. Metabolism 62:337–40
    [Google Scholar]
  63. 63.
    Nguyen HP, Lin F, Yi D, Xie Y, Dinh J et al. 2021. Aging-dependent regulatory cells emerge in subcutaneous fat to inhibit adipogenesis. Dev. Cell 56:1437–51
    [Google Scholar]
  64. 64.
    Wang QA, Tao C, Gupta RK, Scherer PE. 2013. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat. Med. 19:1338–44
    [Google Scholar]
  65. 65.
    Yamamuro T, Kawabata T, Fukuhara A, Saita S, Nakamura S et al. 2020. Age-dependent loss of adipose Rubicon promotes metabolic disorders via excess autophagy. Nat. Commun. 11:4150
    [Google Scholar]
  66. 66.
    Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL et al. 2013. Metformin improves healthspan and lifespan in mice. Nat. Commun. 4:2192
    [Google Scholar]
  67. 67.
    Le Pelletier L, Mantecon M, Gorwood J, Auclair M, Foresti R 2021. Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction. Elife 10:62635
    [Google Scholar]
  68. 68.
    Kalender A, Selvaraj A, Kim SY, Gulati P, Brule S et al. 2010. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab. 11:390–401
    [Google Scholar]
  69. 69.
    He L, Wondisford FE. 2015. Metformin action: concentrations matter. Cell Metab. 21:159–62
    [Google Scholar]
  70. 70.
    Tabuchi C, Sul HS. 2021. Signaling pathways regulating thermogenesis. Front. Endocrinol. 12:595020
    [Google Scholar]
  71. 71.
    Winkler E, Klingenberg M. 1994. Effect of fatty acids on H+ transport activity of the reconstituted uncoupling protein. J. Biol. Chem. 269:2508–15
    [Google Scholar]
  72. 72.
    Bordicchia M, Liu D, Amri E, Ailhaud G, Dessi-Fulgheri P et al. 2012. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J. Clin. Investig. 122:1022–36
    [Google Scholar]
  73. 73.
    Fisher FM, Kleiner S, Douris N, Fox EC, Mepani RJ et al. 2012. FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis. Genes Dev. 26:271–81
    [Google Scholar]
  74. 74.
    Gaudry MJ, Jastroch M, Treberg JR, Hofreiter M, Paijmans JL et al. 2017. Inactivation of thermogenic UCP1 as a historical contingency in multiple placental mammal clades. Sci. Adv. 3:1602878
    [Google Scholar]
  75. 75.
    Periasamy M, Maurya SK, Sahoo SK, Singh S, Sahoo SK et al. 2017. Role of SERCA pump in muscle thermogenesis and metabolism. Compr. Physiol. 7:879–90
    [Google Scholar]
  76. 76.
    Arruda AP, Nigro M, Oliveira GM, de Meis L. 2007. Thermogenic activity of Ca2+-ATPase from skeletal muscle heavy sarcoplasmic reticulum: the role of ryanodine Ca2+ channel. Biochim. Biophys. Acta Biomembr. 1768:1498–505
    [Google Scholar]
  77. 77.
    Bal NC, Maurya SK, Sopariwala DH, Sahoo SK, Gupta SC et al. 2012. Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals. Nat. Med. 18:1575–79
    [Google Scholar]
  78. 78.
    Ikeda K, Kang Q, Yoneshiro T, Camporez JP, Maki H et al. 2017. UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis. Nat. Med. 23:1454–65
    [Google Scholar]
  79. 79.
    Kang S, Dahl R, Hsieh W, Shin A, Zsebo KM et al. 2016. Small molecular allosteric activator of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) attenuates diabetes and metabolic disorders. J. Biol. Chem. 291:5185–98
    [Google Scholar]
  80. 80.
    Tajima K, Ikeda K, Tanabe Y, Thomson EA, Yoneshiro T et al. 2020. Wireless optogenetics protects against obesity via stimulation of non-canonical fat thermogenesis. Nat. Commun. 11:1730
    [Google Scholar]
  81. 81.
    Kim CK, Adhikari A, Deisseroth K. 2017. Integration of optogenetics with complementary methodologies in systems neuroscience. Nat. Rev. Neurosci. 18:222–35
    [Google Scholar]
  82. 82.
    Kazak L, Chouchani ET, Jedrychowski MP, Erickson BK, Shinoda K et al. 2015. A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. Cell 163:643–55
    [Google Scholar]
  83. 83.
    Kazak L, Rahbani JF, Samborska B, Lu GZ, Jedrychowski MP et al. 2019. Ablation of adipocyte creatine transport impairs thermogenesis and causes diet-induced obesity. Nat. Metab. 1:360–70
    [Google Scholar]
  84. 84.
    Rahbani JF, Roesler A, Hussain MF, Samborska B, Dykstra CB et al. 2021. Creatine kinase B controls futile creatine cycling in thermogenic fat. Nature 590:480–85
    [Google Scholar]
  85. 85.
    Sun Y, Rahbini JF, Jedrychowski MP, Riley CL, Vidoni S et al. 2021. Mitochondrial TNAP controls thermogenesis by hydrolysis of phosphocreatine. Nature 593:580–85
    [Google Scholar]
  86. 86.
    Connell NJ, Doligkeit D, Andriessen C, Kornips-Moonen E, Bruls YM et al. 2021. No evidence for brown adipose tissue activation after creatine supplementation in adult vegetarians. Nat. Metab. 3:107–17
    [Google Scholar]
  87. 87.
    Reidy SP, Weber JM. 2002. Accelerated substrate cycling: a new energy-wasting role for leptin in vivo. Am. J. Physiol. Endocrinol. Metab. 282:312–17
    [Google Scholar]
  88. 88.
    Mottillo EP, Balasubramanian P, Lee Y, Weng C, Kershaw EE, Granneman JG. 2014. Coupling of lipolysis and de novo lipogenesis in brown, beige, and white adipose tissues during chronic β3-adrenergic receptor activation. J. Lipid Res. 55:2276–86
    [Google Scholar]
  89. 89.
    Guan HP, Li Y, Jensen MV, Newgard CB, Steppan CM, Lazar MA. 2002. A futile metabolic cycle activated in adipocytes by antidiabetic agents. Nat. Med. 8:1122–28
    [Google Scholar]
  90. 90.
    Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM. 2003. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Circulation 108:2941–48
    [Google Scholar]
  91. 91.
    Divakaruni AS, Wiley SE, Rogers GW, Andreyev AY, Petrosyan S et al. 2013. Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier. PNAS 110:5422–27
    [Google Scholar]
  92. 92.
    Harrison SA, Alkhouri N, Davison BA, Sanyal A, Edwards C. 2020. Insulin sensitizer MSDC-0602K in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase IIb study. J. Hepatol. 72:613–26
    [Google Scholar]
  93. 93.
    von Haehling S, Anker SD. 2014. Prevalence, incidence and clinical impact of cachexia: facts and numbers—update 2014. J. Cachexia Sarcopenia Muscle 5:261–63
    [Google Scholar]
  94. 94.
    Das SK, Eder S, Schauer S, Diwoky C, Temmel H et al. 2011. Adipose triglyceride lipase contributes to cancer-associated cachexia. Science 333:233–38
    [Google Scholar]
  95. 95.
    Brejchova K, Radner FP, Balas L, Paluchova V, Cajka T et al. 2021. Distinct roles of adipose triglyceride lipase and hormone-sensitive lipase in the catabolism of triacylglycerol estolides. PNAS 118:2020999118
    [Google Scholar]
  96. 96.
    Unger RH. 2002. Lipotoxic diseases. Ann. Rev. Med. 53:319–36
    [Google Scholar]
  97. 97.
    Malhi H, Bronk SF, Werneburg NW, Gores GJ. 2006. Free fatty acids induce JNK-dependent hepatocyte lipoapoptosis. J. Biol. Chem. 281:12093–101
    [Google Scholar]
  98. 98.
    Brooks SL, Neville AM, Rothwell NJ, Stock MJ, Wilson S 1981. Sympathetic activation of brown-adipose-tissue thermogenesis in cachexia. Biosci. Rep. 1:509–17
    [Google Scholar]
  99. 99.
    Shellock FG, Riedinger MS, Fishbein MC. 1986. Brown adipose tissue in cancer patients: possible cause of cancer-induced cachexia. J. Cancer Res. Clin. Oncol. 111:82–85
    [Google Scholar]
  100. 100.
    Petruzzelli M, Schweiger M, Schreiber R, Campos-Olivas R, Tsoli M et al. 2014. A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab. 20:433–47
    [Google Scholar]
  101. 101.
    Kir S, White JP, Kleiner S, Kazak L, Cohen P et al. 2014. Tumor-derived PTHrP triggers adipose tissue browning and cancer cachexia. Nature 513:100–4
    [Google Scholar]
  102. 102.
    Wei G, Sun H, Dong K, Hu L, Wang Q et al. 2021. The thermogenic activity of adjacent adipocytes fuels the progression of ccRCC and compromises anti-tumor therapeutic efficacy. Cell Metab. 33:2021–39
    [Google Scholar]
  103. 103.
    Auger C, Samadi O, Jeschke MG. 2017. The biochemical alterations underlying post-burn hypermetabolism. Biochim. Biophys. Acta. Mol. Basis Dis. 1863:2633–44
    [Google Scholar]
  104. 104.
    Auger C, Sivayoganathan T, Abdullahi A, Parousis A, Pang BW, Jeschke MG. 2018. Metformin adapts its cellular effects to bioenergetic status in a model of metabolic dysfunction. Sci. Rep. 8:5646
    [Google Scholar]
  105. 105.
    Jeschke MG, Kulp GA, Kraft R, Finnerty CC, Mlcak R et al. 2010. Intensive insulin therapy in severely burned pediatric patients: a prospective randomized trial. Am. J. Respir. Crit. Care Med. 182:351–59
    [Google Scholar]
  106. 106.
    Kaur S, Auger C, Jeschke MG. 2020. Adipose tissue metabolic function and dysfunction: impact of burn injury. Front. Cell Dev. Biol. 8:599576
    [Google Scholar]
  107. 107.
    Kulp GA, Herndon DN, Lee JO, Suman OE, Jeschke MG. 2010. Extent and magnitude of catecholamine surge in pediatric burned patients. Shock 33:369–74
    [Google Scholar]
  108. 108.
    Patsouris D, Qi P, Abdullahi A, Stanojcic M, Chen P et al. 2015. Burn induces browning of the subcutaneous white adipose tissue in mice and humans. Cell Rep. 13:1538–44
    [Google Scholar]
  109. 109.
    Sidossis LS, Porter C, Saraf MK, Borsheim E, Radhakrishnan RS et al. 2015. Browning of subcutaneous white adipose tissue in humans after severe adrenergic stress. Cell Metab. 22:219–27
    [Google Scholar]
  110. 110.
    Abdullahi A, Auger C, Stanojcic M, Patsouris D, Parousis A et al. 2019. Alternatively activated macrophages drive browning of white adipose tissue in burns. Ann. Surg. 269:554–63
    [Google Scholar]
  111. 111.
    Abdullahi A, Samadi O, Auger C, Kanagalingam T, Boehning D et al. 2019. Browning of white adipose tissue after a burn injury promotes hepatic steatosis and dysfunction. Cell Death Dis. 10:870
    [Google Scholar]
  112. 112.
    Auger C, Knuth CM, Abdullahi A, Samadi O, Parousis A, Jeschke MG. 2019. Metformin prevents the pathological browning of subcutaneous white adipose tissue. Mol. Metab. 29:12–23
    [Google Scholar]
  113. 113.
    Barayan D, Abdullahi A, Vinaik R, Knuth CM, Auger C, Jeschke MG. 2021. Interleukin-6 blockade, a potential adjunct therapy for post-burn hypermetabolism. FASEB J. 35:21596
    [Google Scholar]
  114. 114.
    Barayan D, Vinaik R, Auger C, Knuth CM, Abdullahi A, Jeschke MG. 2020. Inhibition of lipolysis with acipimox attenuates postburn white adipose tissue browning and hepatic fat infiltration. Shock 53:137–45
    [Google Scholar]
  115. 115.
    Kaur S, Auger C, Barayan D, Shah P, Matveev A et al. 2021. Adipose-specific ATGL ablation reduces burn injury-induced metabolic derangements in mice. Clin. Transl. Med. 11:417
    [Google Scholar]
  116. 116.
    Ayalon I, Shen H, Williamson L, Stringer K, Zingarelli B, Kaplan JM. 2018. Sepsis induces adipose tissue browning in nonobese mice but not in obese mice. Shock 50:557–64
    [Google Scholar]
  117. 117.
    Li C, Davis X, Lahni P, Stuck J, Williamson L, Kaplan J. 2021. Obesity protects against sepsis-induced and norepinephrine-induced white adipose tissue browning. Am. J. Physiol. Endocrinol. Metab. 321:433–42
    [Google Scholar]
  118. 118.
    Jagan N, Morrow LE, Walters RW, Plambeck RW, Wallen TJ et al. 2020. Sepsis and the obesity paradox: size matters in more than one way. Crit. Care Med. 48:776–82
    [Google Scholar]
  119. 119.
    Jeschke MG, Finnerty CC, Emdad F, Rivero HG, Kraft R et al. 2013. Mild obesity is protective after severe burn injury. Ann. Surg. 258:1119–29
    [Google Scholar]
  120. 120.
    Cespedes Feliciano EM, Kroenke CH, Caan BJ 2018. The obesity paradox in cancer: how important is muscle?. Annu. Rev. Nutr. 38:357–79
    [Google Scholar]
  121. 121.
    Knuth CM, Auger C, Chi L, Barayan D, Abdullahi A, Jeschke MG 2021. Thermal stress induces long-term remodeling of adipose tissue and is associated with systemic dysfunction. Shock 56:744–54
    [Google Scholar]
  122. 122.
    Yamazawa T, Kobayashi T, Kurebayashi N, Konishi M, Noguchi S et al. 2021. A novel Ryr1-selective inhibitor prevents and rescues sudden death in mouse models of malignant hyperthermia and heat stroke. Nat. Commun. 12:4293
    [Google Scholar]
  123. 123.
    Wang HJ, Lee CS, Zhen Yee RS, Groom L, Friedman I et al. 2020. Adaptive thermogenesis enhances the life-threatening response to heat in mice with an Ryr1 mutation. Nat. Commun. 11:5099
    [Google Scholar]
  124. 124.
    Chen SX, Zhang LJ, Gallo RL. 2019. Dermal white adipose tissue: a newly recognized layer of skin innate defense. J. Investig. Dermatol. 139:1002–9
    [Google Scholar]
  125. 125.
    Zhang Z, Shao M, Hepler C, Zi Z, Zhao S et al. 2019. Dermal adipose tissue has high plasticity and undergoes reversible dedifferentiation in mice. J. Clin. Investig. 129:5327–42
    [Google Scholar]
  126. 126.
    Alexander CM, Kasza I, Yen CE, Reeder SB, Hernando D et al. 2015. Dermal white adipose tissue: a new component of the thermogenic response. J. Lipid Res. 56:2061–69
    [Google Scholar]
  127. 127.
    Zhang LJ, Guerrero-Juarez CF, Hata T, Bapat SP, Ramos R et al. 2015. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection. Science 347:67–71
    [Google Scholar]
  128. 128.
    Nicu C, O'Sullivan JD, Ramos R, Timperi L, Lai T et al. 2021. Dermal adipose tissue secretes HGF to promote human hair growth and pigmentation. J. Investig. Dermatol. 141:1633–45
    [Google Scholar]
  129. 129.
    Shook BA, Wasko RR, Mano O, Rutenberg-Schoenberg M, Rudolph MC et al. 2020. Dermal adipocyte lipolysis and myofibroblast conversion are required for efficient skin repair. Cell Stem Cell 26:880–95
    [Google Scholar]
  130. 130.
    Piccolo NS, Piccolo MS, Piccolo MTS. 2015. Fat grafting for treatment of burns, burn scars, and other difficult wounds. Clin. Plast. Surg. 42:263–83
    [Google Scholar]
  131. 131.
    Lee G, Hunter-Smith DJ, Rozen WM. 2017. Autologous fat grafting in keloids and hypertrophic scars: a review. Scars Burn. Heal. 3:205951311770015
    [Google Scholar]
  132. 132.
    Byrne M, O'Donnell M, Fitzgerald L, Shelley OP 2016. Early experience with fat grafting as an adjunct for secondary burn reconstruction in the hand: technique, hand function assessment and aesthetic outcomes. Burns 42:356–65
    [Google Scholar]
  133. 133.
    Koethe JR, Lagathu C, Lake JE, Domingo P, Calmy A et al. 2020. HIV and antiretroviral therapy-related fat alterations. Nat. Rev. Dis. Prim. 6:1–20
    [Google Scholar]
  134. 134.
    Patni N, Garg A. 2015. Congenital generalized lipodystrophies—new insights into metabolic dysfunction. Nat. Rev. Endocrinol. 11:522–34
    [Google Scholar]
  135. 135.
    Mann JP, Savage DB. 2019. What lipodystrophies teach us about the metabolic syndrome. J. Clin. Investig. 129:4009–21
    [Google Scholar]
  136. 136.
    Combs TP, Mukherjee NS, de Almeida CJ, Jelicks LA, Schubert W et al. 2005. The adipocyte as an important target cell for Trypanosoma cruzi infection. J. Biol. Chem. 280:24085–94
    [Google Scholar]
  137. 137.
    Martinez N, Cheng CY, Ketheesan N, Cullen A, Tang Y et al. 2019. mTORC2/Akt activation in adipocytes is required for adipose tissue inflammation in tuberculosis. EBioMedicine 45:314–27
    [Google Scholar]
  138. 138.
    Reiterer M, Rajan M, Gomez-Banoy N, Lau JD, Gomez-Escobar LG et al. 2021. Hyperglycemia in acute COVID-19 is characterized by insulin resistance and adipose tissue infectivity by SARS-CoV-2. Cell Metab. 33:2174–88
    [Google Scholar]
  139. 139.
    Machado H, Bizarra-Rebelo T, Costa-Sequeira M, Trindade S, Carvalho T et al. 2021. Trypanosoma brucei triggers a broad immune response in the adipose tissue. PLOS Pathog. 17:e1009933
    [Google Scholar]
  140. 140.
    Trindade S, Rijo-Ferreira F, Carvalho T, Pinto-Neves D, Guegan F et al. 2016. Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice. Cell Host Microbe 19:837–48
    [Google Scholar]
  141. 141.
    Ayyappan JP, Ganapathi U, Lizardo K, Vinnard C, Subbian S et al. 2019. Adipose tissue regulates pulmonary pathology during TB infection. MBio 10:e02771–18
    [Google Scholar]
  142. 142.
    van der Windt GJW, Pearce EL 2012. Metabolic switching and fuel choice during T-cell differentiation and memory development. Immunol. Rev. 249:27–42
    [Google Scholar]
  143. 143.
    Anuradha R, Munisankar S, Bhootra Y, Dolla C, Kumaran P, Babu S. 2016. High body mass index is associated with heightened systemic and mycobacterial antigen – specific pro-inflammatory cytokines in latent tuberculosis. Tuberculosis 101:56–61
    [Google Scholar]
  144. 144.
    Gupta RK, Mepani RJ, Kleiner S, Lo JC, Khandekar MJ et al. 2013. ZFP423 expression identified committed preadipocytes and localizes to adipose endothelial and perivascular cells. Cell Metab. 15:230–39
    [Google Scholar]
  145. 145.
    Rodeheffer MS, Birsoy K, Friedman JM. 2008. Identification of white adipocyte progenitor cells in vivo. Cell 135:240–49
    [Google Scholar]
  146. 146.
    Berry R, Rodeheffer MS. 2013. Characterization of the adipocyte cellular lineage in vivo. Nat. Cell Biol. 15:302–8
    [Google Scholar]
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