Skip to main content
SpringerLink
Log in

The Different Shades of Thermogenic Adipose Tissue

  • REVIEW
  • Published:
Current Obesity Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

By providing a concise overview of adipose tissue types, elucidating the regulation of adipose thermogenic capacity in both physiological contexts and chronic wasting diseases (a protracted hypermetabolic state that precipitates sustained catabolism and consequent progressive corporeal atrophy), and most importantly, delving into the ongoing discourse regarding the role of adipose tissue thermogenic activation in chronic wasting diseases, this review aims to provide researchers with a comprehensive understanding of the field.

Recent Findings

Adipose tissue, traditionally classified as white, brown, and beige (brite) based on its thermogenic activity and potential, is intricately regulated by complex mechanisms in response to exercise or cold exposure. This regulation is adipose depot-specific and dependent on the duration of exposure. Excessive thermogenic activation of adipose tissue has been observed in chronic wasting diseases and has been considered a pathological factor that accelerates disease progression. However, this conclusion may be confounded by the detrimental effects of excessive lipolysis. Recent research also suggests that such activation may play a beneficial role in the early stages of chronic wasting disease and provide potential therapeutic effects.

Summary

A more comprehensive understanding of the changes in adipose tissue thermogenesis under physiological and pathological conditions, as well as the underlying regulatory mechanisms, is essential for the development of novel interventions to improve health and prevent disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

No datasets were generated or analysed during the current study.

Abbreviations

ACE2:

Angiotensin-converting enzyme 2

ADRB1 :

Adrenoceptor beta 1

ADRB2 :

Adrenoceptor beta 2

ADRB3 :

Adrenoceptor beta 3

Akt:

The serine/threonine kinase

AMPK:

AMP-activated protein kinase

ANP:

Atrial natriuretic peptide

ATGL:

Adipose triglyceride lipase

BAT:

Brown adipose tissue

β2-AR:

Beta2-adrenergic receptor

β3-AR:

Beta3-adrenergic receptor

BNP:

Brain natriuretic peptide

CAC:

Cancer-associated cachexia

cAMP:

Cyclic adenosine monophosphate

CKD:

Chronic kidney disease

COX4:

Cytochrome C oxidase subunit 4

COVID-19:

Corona Virus Disease 2019

ECM:

Extracellular matrix

eWAT:

Epididymal white adipose tissue

EPDR1:

Ependymin related 1

ER:

Endoplasmic reticulum

ErbB4:

Epidermal growth factor receptor 4

18F-FDG:

F-18 fluorodeoxyglucose

FABP4:

Fatty acid-binding protein 4

FAHFA:

Fatty acid esters of hydroxy fatty acid

FFAs:

Free fatty acids

FGF21:

Fibroblast growth factor 21

FNDC5:

Fibronectin type III domain-containing 5

GDF15:

Growth differentiation factor 15

GLP-1:

Glucagon-like peptide 1

H3K9me2:

Histone H3 lysine 9 dimethylation

HFD:

Igh-fat diet

HSL:

Hormone-sensitive lipase

iBAT:

Interscapular brown adipose tissue

IFN-γ:

Interferon-1gamma

IL-1β:

Interleukin-1beta

IL-10:

Interleukin-10

IL-17:

Interleukin-17

IL-6:

Interleukin-6

IL-8:

Interleukin-8

iWAT:

Inguinal white adipose tissue

JAK/Stat3:

Janus kinase/signal transducer and activator of transcription 3

LEP-R:

Leptin receptor

MI/R:

Myocardial ischemia/reperfusion

Myh11:

Myosin heavy chain 11

ND:

Normal diet

NEFA:

Non-esterified fatty acids

NF-κB:

Nuclear factor kappa-B

NLRP3:

NOD-like receptor family pyrin domain containing 3

NRG4:

Neuregulin 4

NOS1:

Nitric oxide synthase 1

PCOS:

Polycystic ovary syndrome

PDGFRα:

Platelet-derived growth factor receptor alpha

PET/CT:

Positron emission tomography/computed tomography

PGC1α:

Peroxisome proliferator-activated receptor-gamma coactivator-1alpha

PKA:

Protein kinase A

Prdm16:

PR domain-containing 16

PTH:

Parathyroid hormone

PTHrP:

Parathyroid-hormone-related protein

PVAT:

Perivascular adipose tissue

REE:

Resting energy expenditure

SARS-CoV-2:

Severe acute respiratory syndrome coronavirus 2

SCA1:

Spinocerebellar ataxia type 1

sEVs:

Small extracellular vesicles

SNS:

Sympathetic nervous system

sWAT:

Subcutaneous white adipose tissue

TG:

Triglycerides

TGFβ:

Transforming growth factor-beta

TH:

Thyroid hormone

TMEM26:

Transmembrane protein 26

TNBS:

2, 4, 6-Trinitrobenzenesufonic acid

TNFα:

Tumor necrosis factor-alpha

T2DM:

Type 2 diabetes mellitus

UCP1:

Uncoupling protein 1

vWAT:

Visceral white adipose tissue

WAT:

White adipose tissue

ZAG:

Zinc alpha2 glycoprotein

11C-HED:

11C-meta-hydroxyephedrine

12,13-diHOME:

12,13-Dihydroxy-9Z-octadecenoic acid

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Cypess AM. Reassessing human adipose tissue. N Engl J Med. 2022;386(8):768–79.

    Article  CAS  PubMed  Google Scholar 

  2. Wu J, Bostrom P, Sparks LM, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150(2):366–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Pilkington AC, Paz HA, Wankhade UD. beige adipose tissue identification and marker specificity-overview. Front Endocrinol (Lausanne). 2021;12: 599134.

    Article  PubMed  Google Scholar 

  4. •• Ruan CC, Kong LR, Chen XH, et al. A(2A) receptor activation attenuates hypertensive cardiac remodeling via promoting brown adipose tissue-derived FGF21. Cell Metab. 2018;28(3):476–89. This paper demonstrates that A2AR-mediated FGF21 release from brown adipose tissue plays an endocrine protective role against hypertensive cardiac remodeling.

    Article  CAS  PubMed  Google Scholar 

  5. •• Adachi Y, Ueda K, Nomura S, et al. Beiging of perivascular adipose tissue regulates its inflammation and vascular remodeling. Nat Commun. 2022;13(1):5117. This study demonstrates the pivotal roles of perivascular adipose tissue (PVAT) in vascular inflammation and remodeling.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. •• Zhao H, Chen X, Hu G, et al. Small extracellular vesicles from brown adipose tissue mediate exercise cardioprotection. Circ Res. 2022;130(10):1490–506. The small extracellular vesicles (sEVs) secreted by BAT participate in exercise cardioprotection via delivering the cardioprotective miRNAs into the heart.

    Article  CAS  PubMed  Google Scholar 

  7. •• Lin JR, Ding LL, Xu L, et al. Brown adipocyte ADRB3 mediates cardioprotection via suppressing exosomal iNOS. Circ Res. 2022;131(2):133–47. This study demonstrates that the activation of ADRB3 (β3-adrenergic receptors) in brown adipocytes offers cardiac protection through suppressing exosomal iNOS, illustrating an important role of ADRB3 in endocrine crosstalk between BAT and the heart.

    Article  CAS  PubMed  Google Scholar 

  8. Park A, Kim W, Bae K. Distinction of white, beige and brown adipocytes derived from mesenchymal stem cells. World journal of stem cells. 2014;6(1):33–42.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Trayhurn P, Beattie JH. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc. 2001;60(3):329–39.

    Article  CAS  PubMed  Google Scholar 

  10. Scheja L, Heeren J. The endocrine function of adipose tissues in health and cardiometabolic disease. Nat Rev Endocrinol. 2019;15(9):507–24.

    Article  CAS  PubMed  Google Scholar 

  11. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Perry RJ, Camporez JG, Kursawe R, et al. Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes. Cell. 2015;160(4):745–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Item F, Konrad D. Visceral fat and metabolic inflammation: the portal theory revisited. Obes Rev. 2012;13(Suppl 2):30–9.

    Article  PubMed  Google Scholar 

  14. Shamsi F, Wang CH, Tseng YH. The evolving view of thermogenic adipocytes - ontogeny, niche and function. Nat Rev Endocrinol. 2021;17(12):726–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Carpentier AC, Blondin DP, Haman F, Richard D. Brown adipose tissue—a translational perspective. Endocr Rev. 2023;44(2):143–92.

    Article  PubMed  Google Scholar 

  16. Villarroya F, Cereijo R, Villarroya J, Giralt M. Brown adipose tissue as a secretory organ. Nat Rev Endocrinol. 2017;13(1):26–35.

    Article  CAS  PubMed  Google Scholar 

  17. Cannon B, Nedergaard JAN. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84(1):277–359.

    Article  CAS  PubMed  Google Scholar 

  18. Kajimura S, Spiegelman BM, Seale P. Brown and beige fat: physiological roles beyond heat generation. Cell Metab. 2015;22(4):546–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Virtanen KA, Lidell ME, Orava J, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009;360(15):1518–25.

    Article  CAS  PubMed  Google Scholar 

  20. Saito M, Okamatsu-Ogura Y, Matsushita M, et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009;58(7):1526–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Berry DC, Stenesen D, Zeve D, Graff JM. The developmental origins of adipose tissue. Development. 2013;140(19):3939–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  23. Seale P, Conroe HM, Estall J, et al. PRDM16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest. 2011;121(1).

  24. Cohen P, Levy JD, Zhang Y, et al. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell. 2014;156(1–2):304–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang W, Ishibashi J, Trefely S, et al. A PRDM16-driven metabolic signal from adipocytes regulates precursor cell fate. Cell Metab. 2019;30(1).

  26. Henegar C, Tordjman J, Achard V, et al. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol. 2008;9(1):R14.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Muir LA, Neeley CK, Meyer KA, et al. Adipose tissue fibrosis, hypertrophy, and hyperplasia: correlations with diabetes in human obesity. Obesity. 2016;24(3):597–605.

    Article  CAS  PubMed  Google Scholar 

  28. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013;19(10):1252–63.

    Article  CAS  PubMed  Google Scholar 

  29. Long JZ, Svensson KJ, Tsai L, et al. A smooth muscle-like origin for beige adipocytes. Cell Metab. 2014;19(5):810–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Oguri Y, Shinoda K, Kim H, et al. CD81 controls beige fat progenitor cell growth and energy balance via FAK signaling. Cell. 2020;182(3):563-577.e520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bartelt A, Heeren J. Adipose tissue browning and metabolic health. Nat Rev Endocrinol. 2014;10(1):24–36.

    Article  CAS  PubMed  Google Scholar 

  32. Giordano A, Smorlesi A, Frontini A, Barbatelli G, Cinti S. Mechanisms in endocrinology: white, brown and pink adipocytes: the extraordinary plasticity of the adipose organ. Eur J Endocrinol. 2014;170(5):R159–71.

    Article  CAS  PubMed  Google Scholar 

  33. Cinti S. Pink Adipocytes. Trends Endocrinol Metab. 2018;29(9):651–66.

    Article  CAS  PubMed  Google Scholar 

  34. Smorlesi A, Frontini A, Giordano A, Cinti S. The adipose organ: white-brown adipocyte plasticity and metabolic inflammation. Obes Rev. 2012;13(2):83–96.

  35. Morroni M, Giordano A, Zingaretti MC, et al. Reversible transdifferentiation of secretory epithelial cells into adipocytes in the mammary gland. Proc Natl Acad Sci. 2004;101(48):16801–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Shackleton M, Vaillant F, Simpson KJ, et al. Generation of a functional mammary gland from a single stem cell. Nature. 2006;439(7072):84–8.

    Article  CAS  PubMed  Google Scholar 

  37. Prokesch A, Smorlesi A, Perugini J, et al. Molecular aspects of adipoepithelial transdifferentiation in mouse mammary gland. Stem Cells. 2014;32(10):2756–66.

    Article  CAS  PubMed  Google Scholar 

  38. Cinti S, Cigolini M, Morroni M, Zingaretti MC. S-100 protein in white preadipocytes: an immunoelectronmicroscopic study. Anat Rec. 1989;224(4):466–72.

    Article  CAS  PubMed  Google Scholar 

  39. Giordano A, Perugini J, Kristensen DM, et al. Mammary alveolar epithelial cells convert to brown adipocytes in post-lactating mice. J Cell Physiol. 2017;232(11):2923–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Li L, Li B, Li M, et al. Brown adipocytes can display a mammary basal myoepithelial cell phenotype in vivo. Molecular Metabolism. 2017;6(10):1198–211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wagner K-U, Boulanger CA, Henry MD, Sgagias M, Hennighausen L, Smith GH. An adjunct mammary epithelial cell population in parous females: its role in functional adaptation and tissue renewal. Development. 2002;129(6):1377–86.

    Article  CAS  PubMed  Google Scholar 

  42. Wagner KU, Wall RJ, St-Onge L, et al. Cre-mediated gene deletion in the mammary gland. Nucleic Acids Res. 1997;25(21):4323–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hennighausen LG, Sippel AE. Mouse whey acidic protein is a novel member of the family of ‘four-disulfide core’ proteins. Nucleic Acids Res. 1982;10(8):2677–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Smith-Kirwin SM, O’Connor DM, De Johnston J, Lancey ED, Hassink SG, Funanage VL. Leptin expression in human mammary epithelial cells and breast milk. J Clin Endocrinol Metab. 1998;83(5):1810–3.

    Article  CAS  PubMed  Google Scholar 

  45. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425–32.

    Article  CAS  PubMed  Google Scholar 

  46. Friedman J. The long road to leptin. J Clin Investig. 2016;126(12):4727–34.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Fang H, Judd RL. Adiponectin regulation and function. Compr Physiol. 2018;8(3):1031–63.

    Article  PubMed  Google Scholar 

  48. Kim J-Y, van de Wall E, Laplante M, et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Investig. 2007;117(9):2621–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ye R, Wang M, Wang Q, Scherer P. Adiponectin-mediated antilipotoxic effects in regenerating pancreatic islets. Endocrinology. 2015;156(6):2019–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mandal P, Pratt BT, Barnes M, McMullen MR, Nagy LE. Molecular mechanism for adiponectin-dependent M2 macrophage polarization: link between the metabolic and innate immune activity of full-length adiponectin. J Biol Chem. 2011;286(15):13460–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Caligiuri A, Bertolani C, Guerra CT, et al. Adenosine monophosphate-activated protein kinase modulates the activated phenotype of hepatic stellate cells. Hepatology. 2008;47(2):668–76.

    Article  CAS  PubMed  Google Scholar 

  52. Hotamisligil GS, Bernlohr DA. Metabolic functions of FABPs–mechanisms and therapeutic implications. Nat Rev Endocrinol. 2015;11(10):592–605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. McCullough RL, McMullen MR, Sheehan MM, et al. Complement factor D protects mice from ethanol-induced inflammation and liver injury. Am J Physiol Gastrointest Liver Physiol. 2018;315(1):G66–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Scheele C, Wolfrum C. Brown adipose crosstalk in tissue plasticity and human metabolism. Endocr Rev. 2020;41(1):53–65.

    Article  PubMed  Google Scholar 

  55. BonDurant LD, Ameka M, Naber MC, et al. FGF21 regulates metabolism through adipose-dependent and -independent mechanisms. Cell Metab. 2017;25(4).

  56. Schlein C, Talukdar S, Heine M, et al. FGF21 lowers plasma triglycerides by accelerating lipoprotein catabolism in white and brown adipose tissues. Cell Metab. 2016;23(3):441–53.

    Article  CAS  PubMed  Google Scholar 

  57. Lin Z, Tian H, Lam KSL, et al. Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice. Cell Metab. 2013;17(5):779–89.

    Article  CAS  PubMed  Google Scholar 

  58. Geng L, Lam KSL, Xu A. The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic. Nat Rev Endocrinol. 2020;16(11):654–67.

    Article  CAS  PubMed  Google Scholar 

  59. Wang GX, Zhao XY, Meng ZX, et al. The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med. 2014;20(12):1436–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Rosell M, Kaforou M, Frontini A, et al. Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice. Am J Physiol Endocrinol Metab. 2014;306(8):E945-964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. •• Shi L, Li Y, Xu X, et al. Brown adipose tissue-derived Nrg4 alleviates endothelial inflammation and atherosclerosis in male mice. Nat Metab. 2022;4(11):1573–90. This study demonstrates that BAT-derived Nrg4 inhibited endothelial inflammation, decreased leukocyte homing and macrophage accumulation, and improved atherosclerotic plaque stability, via the ErbB4–Akt–NF-κB pathway.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Deshmukh AS, Peijs L, Beaudry JL, et al. Proteomics-based comparative mapping of the secretomes of human brown and white adipocytes reveals EPDR1 as a novel batokine. Cell Metab. 2019;30(5).

  63. Cataldo LR, Gao Q, Argemi-Muntadas L, et al. The human batokine EPDR1 regulates β-cell metabolism and function. Molecular Metabolism. 2022;66: 101629.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Pinckard KM, Shettigar VK, Wright KR, et al. A novel endocrine role for the BAT-released lipokine 12,13-diHOME to mediate cardiac function. Circulation. 2021;143(2):145–59.

    Article  CAS  PubMed  Google Scholar 

  65. Machado SA, Pasquarelli-do-Nascimento G, da Silva DS, et al. Browning of the white adipose tissue regulation: new insights into nutritional and metabolic relevance in health and diseases. Nutr Metab (Lond). 2022;19(1):61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Aldiss P, Betts J, Sale C, Pope M, Budge H, Symonds ME. Exercise-induced ‘browning’ of adipose tissues. Metabolism. 2018;81:63–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Zhu Y, Qi Z, Ding S. Exercise-induced adipose tissue thermogenesis and browning: how to explain the conflicting findings? Int J Mol Sci. 2022;23(21).

  68. Kim HJ, Kim YJ, Seong JK. AMP-activated protein kinase activation in skeletal muscle modulates exercise-induced uncoupled protein 1 expression in brown adipocyte in mouse model. J Physiol. 2022;600(10):2359–76.

    Article  CAS  PubMed  Google Scholar 

  69. Picoli CC, Gilio GR, Henriques F, et al. Resistance exercise training induces subcutaneous and visceral adipose tissue browning in Swiss mice. J Appl Physiol (1985). 2020;129(1):66–74.

  70. Wu MV, Bikopoulos G, Hung S, Ceddia RB. Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high fat diet and endurance training in rats: impact on whole-body energy expenditure. J Biol Chem. 2014;289(49):34129–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. May FJ, Baer LA, Lehnig AC, et al. Lipidomic adaptations in white and brown adipose tissue in response to exercise demonstrate molecular species-specific remodeling. Cell Rep. 2017;18(6):1558–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lehnig AC, Dewal RS, Baer LA, et al. Exercise training induces depot-specific adaptations to white and brown adipose tissue. iScience. 2019;11:425–439.

  73. Pino MF, Parsons SA, Smith SR, Sparks LM. Active individuals have high mitochondrial content and oxidative markers in their abdominal subcutaneous adipose tissue. Obesity (Silver Spring). 2016;24(12):2467–70.

    Article  CAS  PubMed  Google Scholar 

  74. Nozu T, Kikuchi K, Ogawa K, Kuroshima A. Effects of running training on in vitro brown adipose tissue thermogenesis in rats. Int J Biometeorol. 1992;36(2):88–92.

    Article  CAS  PubMed  Google Scholar 

  75. Vosselman MJ, Hoeks J, Brans B, et al. Low brown adipose tissue activity in endurance-trained compared with lean sedentary men. Int J Obes (Lond). 2015;39(12):1696–702.

    Article  CAS  PubMed  Google Scholar 

  76. •• Martinez-Tellez B, Sanchez-Delgado G, Acosta FM, et al. No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial. Nat Commun. 2022;13(1):5259. There was no evidence of changes on BAT volume or activity after 24-week supervised exercise intervention combining resistance and endurance training at different intensities in young sedentary adults.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Aldiss P, Lewis JE, Lupini I, et al. Exercise training in obese rats does not induce browning at thermoneutrality and induces a muscle-like signature in brown adipose tissue. Front Endocrinol (Lausanne). 2020;11:97.

    Article  PubMed  Google Scholar 

  78. Sutherland LN, Bomhof MR, Capozzi LC, Basaraba SA, Wright DC. Exercise and adrenaline increase PGC-1{alpha} mRNA expression in rat adipose tissue. J Physiol. 2009;587(Pt 7):1607–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Xu X, Ying Z, Cai M, et al. Exercise ameliorates high-fat diet-induced metabolic and vascular dysfunction, and increases adipocyte progenitor cell population in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol. 2011;300(5):R1115-1125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Motiani P, Virtanen KA, Motiani KK, et al. Decreased insulin-stimulated brown adipose tissue glucose uptake after short-term exercise training in healthy middle-aged men. Diabetes Obes Metab. 2017;19(10):1379–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Otero-Díaz B, Rodríguez-Flores M, Sánchez-Muñoz V, et al. Exercise induces white adipose tissue browning across the weight spectrum in humans. Front Physiol. 2018;9:1781.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Guo Y, Zhang Q, Zheng L, et al. Depot-specific adaption of adipose tissue for different exercise approaches in high-fat diet/streptozocin-induced diabetic mice. Front Physiol. 2023;14:1189528.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Félix-Soriano E, Sáinz N, Gil-Iturbe E, et al. Differential remodeling of subcutaneous white and interscapular brown adipose tissue by long-term exercise training in aged obese female mice. J Physiol Biochem. 2023;79(2):451–65.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Nakhuda A, Josse AR, Gburcik V, et al. Biomarkers of browning of white adipose tissue and their regulation during exercise- and diet-induced weight loss. Am J Clin Nutr. 2016;104(3):557–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. De Matteis R, Lucertini F, Guescini M, et al. Exercise as a new physiological stimulus for brown adipose tissue activity. Nutr Metab Cardiovasc Dis. 2013;23(6):582–90.

    Article  PubMed  Google Scholar 

  86. Stinkens R, Brouwers B, Jocken JW, et al. Exercise training-induced effects on the abdominal subcutaneous adipose tissue phenotype in humans with obesity. J Appl Physiol (Bethesda, Md : 1985). 2018;125(5):1585–1593.

  87. Zouhal H, Jacob C, Delamarche P, Gratas-Delamarche A. Catecholamines and the effects of exercise, training and gender. Sports Med. 2008;38(5):401–23.

    Article  PubMed  Google Scholar 

  88. Notarius CF, Floras JS. Sympathetic neural responses in heart failure during exercise and after exercise training. Clin Sci (Lond). 2021;135(4):651–69.

    Article  PubMed  Google Scholar 

  89. Daniela M, Catalina L, Ilie O, Paula M, Daniel-Andrei I, Ioana B. Effects of exercise training on the autonomic nervous system with a focus on anti-inflammatory and antioxidants effects. Antioxidants (Basel). 2022;11(2).

  90. Pearson MJ, Smart NA. Exercise therapy and autonomic function in heart failure patients: a systematic review and meta-analysis. Heart Fail Rev. 2018;23(1):91–108.

    Article  CAS  PubMed  Google Scholar 

  91. Jeong J, Sprick JD, DaCosta DR, Mammino K, Nocera JR, Park J. Exercise modulates sympathetic and vascular function in chronic kidney disease. JCI Insight. 2023;8(4).

  92. Björntorp P. Hypertension and exercise. Hypertension 1982;4(5 Pt 2):Iii56–59.

  93. Lehmann M, Schmid P, Keul J. Age- and exercise-related sympathetic activity in untrained volunteers, trained athletes and patients with impaired left-ventricular contractility. Eur Heart J. 1984;5 Suppl E:1–7.

  94. Cuevas-Ramos D, Mehta R, Aguilar-Salinas CA. Fibroblast growth factor 21 and browning of white adipose tissue. Front Physiol. 2019;10:37.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008;88(4):1379–406.

    Article  CAS  PubMed  Google Scholar 

  96. Zhang Y, Li R, Meng Y, et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes. 2014;63(2):514–25.

    Article  CAS  PubMed  Google Scholar 

  97. Boström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463–8.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Huh JY, Dincer F, Mesfum E, Mantzoros CS. Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans. Int J Obes (Lond). 2014;38(12):1538–44.

    Article  CAS  PubMed  Google Scholar 

  99. Kim H, Wrann CD, Jedrychowski M, et al. Irisin mediates effects on bone and fat via αV integrin receptors. Cell. 2018;175(7):1756-1768.e1717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Zheng Y, He J, Yang D, et al. Irisin reduces the abnormal reproductive and metabolic phenotypes of PCOS by regulating the activity of brown adipose tissue in mice. Biol Reprod. 2022;107(4):1046–58.

    PubMed  PubMed Central  Google Scholar 

  101. Fox J, Rioux BV, Goulet EDB, et al. Effect of an acute exercise bout on immediate post-exercise irisin concentration in adults: a meta-analysis. Scand J Med Sci Sports. 2018;28(1):16–28.

    Article  CAS  PubMed  Google Scholar 

  102. Guo L, Quan M, Pang W, Yin Y, Li F. Cytokines and exosomal miRNAs in skeletal muscle-adipose crosstalk. Trends Endocrinol Metab. 2023;34(10):666–81.

    Article  CAS  PubMed  Google Scholar 

  103. Labbé SM, Caron A, Bakan I, et al. In vivo measurement of energy substrate contribution to cold-induced brown adipose tissue thermogenesis. Faseb j. 2015;29(5):2046–58.

    Article  PubMed  Google Scholar 

  104. Okamatsu-Ogura Y, Kuroda M, Tsutsumi R, et al. UCP1-dependent and UCP1-independent metabolic changes induced by acute cold exposure in brown adipose tissue of mice. Metabolism. 2020;113: 154396.

    Article  CAS  PubMed  Google Scholar 

  105. •• Song A, Dai W, Jang MJ, et al. Low- and high-thermogenic brown adipocyte subpopulations coexist in murine adipose tissue. J Clin Invest. 2020;130(1):247–57. This study reports the discovery of a low-thermogenic brown adipocyte subpopulation with unique molecular and metabolic features, coexisting with the classical high-thermogenic brown adipocytes in vivo.

    Article  CAS  PubMed  Google Scholar 

  106. Abe Y, Fujiwara Y, Takahashi H, et al. Histone demethylase JMJD1A coordinates acute and chronic adaptation to cold stress via thermogenic phospho-switch. Nat Commun. 2018;9(1):1566.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Chen Y, Ikeda K, Yoneshiro T, et al. Thermal stress induces glycolytic beige fat formation via a myogenic state. Nature. 2019;565(7738):180–5.

    Article  CAS  PubMed  Google Scholar 

  108. Seki T, Yang Y, Sun X, et al. Brown-fat-mediated tumour suppression by cold-altered global metabolism. Nature. 2022;608(7922):421–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Ouellet V, Labbé SM, Blondin DP, et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest. 2012;122(2):545–52.

    Article  PubMed  PubMed Central  Google Scholar 

  110. 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.

    Article  CAS  PubMed  Google Scholar 

  111. Kern PA, Finlin BS, Zhu B, et al. The effects of temperature and seasons on subcutaneous white adipose tissue in humans: evidence for thermogenic gene induction. J Clin Endocrinol Metab. 2014;99(12):E2772-2779.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Blondin DP, Labbé SM, Phoenix S, et al. Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men. J Physiol. 2015;593(3):701–14.

    Article  CAS  PubMed  Google Scholar 

  113. van der Lans AA, Hoeks J, Brans B, et al. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J Clin Invest. 2013;123(8):3395–403.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Muzik O, Mangner TJ, Leonard WR, Kumar A, Granneman JG. Sympathetic innervation of cold-activated brown and white fat in lean young adults. J Nucl Med. 2017;58(5):799–806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Blondin DP, Labbé SM, Tingelstad HC, et al. Increased brown adipose tissue oxidative capacity in cold-acclimated humans. J Clin Endocrinol Metab. 2014;99(3):E438-446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Finlin BS, Memetimin H, Confides AL, et al. Human adipose beiging in response to cold and mirabegron. JCI Insight. 2018;3(15).

  117. Ye L, Wu J, Cohen P, et al. Fat cells directly sense temperature to activate thermogenesis. Proc Natl Acad Sci USA. 2013;110(30):12480–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Shore AM, Karamitri A, Kemp P, Speakman JR, Graham NS, Lomax MA. Cold-induced changes in gene expression in brown adipose tissue, white adipose tissue and liver. PLoS ONE. 2013;8(7): e68933.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Blondin DP, Daoud A, Taylor T, et al. Four-week cold acclimation in adult humans shifts uncoupling thermogenesis from skeletal muscles to brown adipose tissue. J Physiol. 2017;595(6):2099–113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Gordon K, Blondin DP, Friesen BJ, Tingelstad HC, Kenny GP, Haman F. Seven days of cold acclimation substantially reduces shivering intensity and increases nonshivering thermogenesis in adult humans. J Appl Physiol (1985). 2019;126(6):1598–606.

    Article  CAS  PubMed  Google Scholar 

  121. Sakers A, De Siqueira MK, Seale P, Villanueva CJ. Adipose-tissue plasticity in health and disease. Cell. 2022;185(3):419–46.

    Article  CAS  PubMed  Google Scholar 

  122. Singh R, Barrios A, Dirakvand G, Pervin S. Human brown adipose tissue and metabolic health: potential for therapeutic avenues. Cells. 2021;10(11).

  123. Ballard-Croft C, Maass DL, Sikes P, White J, Horton J. Activation of stress-responsive pathways by the sympathetic nervous system in burn trauma. Shock. 2002;18(1):38–45.

    Article  PubMed  Google Scholar 

  124. Tsoli M, Moore M, Burg D, et al. Activation of thermogenesis in brown adipose tissue and dysregulated lipid metabolism associated with cancer cachexia in mice. Cancer Res. 2012;72(17):4372–82.

    Article  CAS  PubMed  Google Scholar 

  125. Jeschke M, Gauglitz G, Kulp G, et al. Long-term persistance of the pathophysiologic response to severe burn injury. PLoS ONE. 2011;6(7): e21245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Stanojcic M, Abdullahi A, Rehou S, Parousis A, Jeschke M. Pathophysiological response to burn injury in adults. Ann Surg. 2018;267(3):576–84.

    Article  PubMed  Google Scholar 

  127. Carter EA, Bonab AA, Hamrahi V, et al. Effects of burn injury, cold stress and cutaneous wound injury on the morphology and energy metabolism of murine brown adipose tissue (BAT) in vivo. Life Sci. 2011;89(3–4):78–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Porter C, Herndon DN, Bhattarai N, et al. Severe burn injury induces thermogenically functional mitochondria in murine white adipose tissue. Shock. 2015;44(3):258–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Sidossis LS, Porter C, Saraf MK, et al. Browning of subcutaneous white adipose tissue in humans after severe adrenergic stress. Cell Metab. 2015;22(2):219–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. •• Knuth CM, Ricciuti Z, Barayan D, et al. Single-nuclei RNA profiling reveals disruption of adipokine and inflammatory signaling in adipose tissue of burn patients. Ann Surg. 2023;278(6):e1267–76. In this cohort study, the authors provide novel insight toward the effect of burns on adipokine release, inflammatory signaling pathways, and adipose heterogeneity during the acute and chronic stages postburn.

    Article  PubMed  Google Scholar 

  131. Thomas SA, Palmiter RD. Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline. Nature. 1997;387(6628):94–7.

    Article  CAS  PubMed  Google Scholar 

  132. Kawakami M, He J, Sakamoto T, Okada Y. Catecholamines play a role in the production of interleukin-6 and interleukin-1alpha in unburned skin after burn injury in mice. Crit Care Med. 2001;29(4):796–801.

    Article  CAS  PubMed  Google Scholar 

  133. Stanford KI, Middelbeek RJW, Townsend KL, et al. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Investig. 2013;123(1):215–23.

    Article  CAS  PubMed  Google Scholar 

  134. Caldwell FT, Wallace BH, Cone JB, Manuel L. Control of the hypermetabolic response to burn injury using environmental factors. Ann Surg. 1992;215(5).

  135. Pei Y, Otieno D, Gu I, et al. Effect of quercetin on nonshivering thermogenesis of brown adipose tissue in high-fat diet-induced obese mice. J Nutr Biochem. 2021;88: 108532.

    Article  CAS  PubMed  Google Scholar 

  136. Blondin DP, Nielsen S, Kuipers EN, et al. Human brown adipocyte thermogenesis is driven by β2-AR stimulation. Cell Metab. 2020;32(2).

  137. Rosenbaum M, Malbon CC, Hirsch J, Leibel RL. Lack of beta 3-adrenergic effect on lipolysis in human subcutaneous adipose tissue. J Clin Endocrinol Metab. 1993;77(2):352–5.

    CAS  PubMed  Google Scholar 

  138. Cao D-x, Wu G-h, Yang Z-a, et al. Role of β1-adrenoceptor in increased lipolysis in cancer cachexia. Cancer Sci. 2010;101(7):1639–45.

    Article  CAS  PubMed  Google Scholar 

  139. Moins-Teisserenc H, Cordeiro DJ, Audigier V, et al. Severe altered immune status after burn injury is associated with bacterial infection and septic shock. Front Immunol. 2021;12: 586195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Jeschke MG, Gauglitz GG, Finnerty CC, Kraft R, Mlcak RP, Herndon DN. Survivors versus nonsurvivors postburn: differences in inflammatory and hypermetabolic trajectories. Ann Surg. 2014;259(4):814–23.

    Article  PubMed  Google Scholar 

  141. Mulder PPG, Koenen HJPM, Vlig M, Joosten I, de Vries RBM, Boekema BKHL. Burn-induced local and systemic immune response: systematic review and meta-analysis of animal studies. J Invest Dermatol. 2022;142(11).

  142. Abdullahi A, Auger C, Stanojcic M, et al. Alternatively activated macrophages drive browning of white adipose tissue in burns. Ann Surg. 2019;269(3):554–63.

    Article  PubMed  Google Scholar 

  143. Babaei R, Schuster M, Meln I, et al. Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis. Sci Signal. 2018;11(527).

  144. Abdullahi A, Samadi O, Auger C, et al. Browning of white adipose tissue after a burn injury promotes hepatic steatosis and dysfunction. Cell Death Dis. 2019;10(12):870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Vinaik R, Barayan D, Abdullahi A, Jeschke MG. NLRP3 inflammasome mediates white adipose tissue browning after burn. Am J Physiol Endocrinol Metab. 2019;317(5):E751–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Kaur S, Auger C, Jeschke MG. Adipose tissue metabolic function and dysfunction: impact of burn injury. Front Cell Dev Biol. 2020;8: 599576.

    Article  PubMed  PubMed Central  Google Scholar 

  147. •• Kaur S, Auger C, Barayan D, et al. Adipose-specific ATGL ablation reduces burn injury-induced metabolic derangements in mice. Clin Transl Med. 2021;11(6): e417. This study demonstrates that countering WAT lipolysis by genetic knockdown and pharmacological inhibition of adipose triglyceride lipase (ATGL) would have therapeutic benefits in hypermetabolic conditions.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Qi P, Abdullahi A, Stanojcic M, Patsouris D, Jeschke MG. Lipidomic analysis enables prediction of clinical outcomes in burn patients. Sci Rep. 2016;6.

  149. Zhao HL, Sui Y, Guan J, et al. Fat redistribution and adipocyte transformation in uninephrectomized rats. Kidney Int. 2008;74(4):467–77.

    Article  CAS  PubMed  Google Scholar 

  150. Abe I, Oguri Y, Verkerke ARP, et al. Lipolysis-derived linoleic acid drives beige fat progenitor cell proliferation. Dev Cell. 2022;57(23):2623-2637.e2628.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Abdullahi A, Jeschke M. Taming the flames: targeting white adipose tissue browning in hypermetabolic conditions. Endocr Rev. 2017;38(6):538–49.

    Article  PubMed  PubMed Central  Google Scholar 

  152. Barayan D, Vinaik R, Auger C, Knuth CM, Abdullahi A, Jeschke MG. Inhibition of lipolysis with acipimox attenuates postburn white adipose tissue browning and hepatic fat infiltration. Shock. 2020;53(2):137–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. •• Auger C, Knuth C, Abdullahi A, Samadi O, Parousis A, Jeschke M. Metformin prevents the pathological browning of subcutaneous white adipose tissue. Molecular metabolism. 2019;29:12–23. This study provides novel insights into the therapeutic benefits of metformin to prevent the lipotoxicity and adipose browning associated with hypermetabolism.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Rydén M, Arner P. Fat loss in cachexia–is there a role for adipocyte lipolysis? Clin Nutr. 2007;26(1):1–6.

    Article  PubMed  Google Scholar 

  155. Shellock F, Riedinger M, Fishbein M. Brown adipose tissue in cancer patients: possible cause of cancer-induced cachexia. J Cancer Res Clin Oncol. 1986;111(1):82–5.

    Article  CAS  PubMed  Google Scholar 

  156. Bianchi A, Bruce J, Cooper A, et al. Increased brown adipose tissue activity in children with malignant disease. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 1989;21(11):640–1.

    Article  CAS  PubMed  Google Scholar 

  157. Oudart H, Calgari C, Andriamampandry M, Le Maho Y, Malan A. Stimulation of brown adipose tissue activity in tumor-bearing rats. Can J Physiol Pharmacol. 1995;73(11):1625–31.

    Article  CAS  PubMed  Google Scholar 

  158. Petruzzelli M, Schweiger M, Schreiber R, et al. A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab. 2014;20(3):433–47.

    Article  CAS  PubMed  Google Scholar 

  159. Lee P, Greenfield JR, Ho KKY, 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.

    Article  CAS  PubMed  Google Scholar 

  160. Becker AS, Zellweger C, Bacanovic S, et al. Brown fat does not cause cachexia in cancer patients: a large retrospective longitudinal FDG-PET/CT cohort study. PLoS ONE. 2020;15(10): e0239990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Brooks SL, Neville AM, Rothwell NJ, Stock MJ, Wilson S. Sympathetic activation of brown-adipose-tissue thermogenesis in cachexia. Biosci Rep. 1981;1(6):509–17.

    Article  CAS  PubMed  Google Scholar 

  162. Anderson LJ, Lee J, Anderson B, et al. Whole-body and adipose tissue metabolic phenotype in cancer patients. J Cachexia Sarcopenia Muscle. 2022;13(2):1124–33.

    Article  PubMed  PubMed Central  Google Scholar 

  163. Pototschnig I, Feiler U, Diwoky C, et al. Interleukin-6 initiates muscle- and adipose tissue wasting in a novel C57BL/6 model of cancer-associated cachexia. J Cachexia Sarcopenia Muscle. 2023;14(1).

  164. •• Xie H, Heier C, Meng X, et al. An immune-sympathetic neuron communication axis guides adipose tissue browning in cancer-associated cachexia. Proc Natl Acad Sci USA. 2022;119(9). This study highlights the important roles of adipose tissue macrophage-sympathetic neuron cross-talk in the metabolic switch toward white adipose tissue catabolism in murine models of Cancer-associated cachexia (CAC).

  165. Pagnotta P, Gantov M, Fletcher S, et al. Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action. Front Endocrinol (Lausanne). 2023;14:1144016.

    Article  PubMed  Google Scholar 

  166. Kir S, White JP, Kleiner S, et al. Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature. 2014;513(7516):100–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Elattar S, Dimri M, Satyanarayana A. The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting. FASEB J. 2018;32(9):4727–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Paré M, Darini CY, Yao X, et al. Breast cancer mammospheres secrete Adrenomedullin to induce lipolysis and browning of adjacent adipocytes. BMC Cancer. 2020;20(1):784.

    Article  PubMed  PubMed Central  Google Scholar 

  169. Hu W, Ru Z, Xiao W, et al. Adipose tissue browning in cancer-associated cachexia can be attenuated by inhibition of exosome generation. Biochem Biophys Res Commun. 2018;506(1):122–9.

    Article  CAS  PubMed  Google Scholar 

  170. Shibata C, Otsuka M, Seimiya T, Kishikawa T, Ishigaki K, Fujishiro M. Lipolysis by pancreatic cancer-derived extracellular vesicles in cancer-associated cachexia via specific integrins. Clin Transl Med. 2022;12(11): e1089.

    Article  PubMed  PubMed Central  Google Scholar 

  171. Di W, Zhang W, Zhu B, Li X, Tang Q, Zhou Y. Colorectal cancer prompted adipose tissue browning and cancer cachexia through transferring exosomal miR-146b-5p. J Cell Physiol. 2021;236(7):5399–410.

    Article  CAS  PubMed  Google Scholar 

  172. Morley JE, Thomas DR, Wilson MM. Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr. 2006;83(4):735–43.

    Article  CAS  PubMed  Google Scholar 

  173. Querfeld U, Mak RH. Vitamin D deficiency and toxicity in chronic kidney disease: in search of the therapeutic window. Pediatr Nephrol. 2010;25(12):2413–30.

    Article  PubMed  Google Scholar 

  174. Malloy PJ, Feldman BJ. Cell-autonomous regulation of brown fat identity gene UCP1 by unliganded vitamin D receptor. Mol Endocrinol. 2013;27(10):1632–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Cheung WW, Ding W, Hoffman HM, et al. Vitamin D ameliorates adipose browning in chronic kidney disease cachexia. Sci Rep. 2020;10(1):14175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Kir S, Komaba H, Garcia AP, et al. PTH/PTHrP receptor mediates cachexia in models of kidney failure and cancer. Cell Metab. 2016;23(2):315–23.

    Article  CAS  PubMed  Google Scholar 

  177. Bordicchia M, Liu D, Amri EZ, et al. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Rial-Pensado E, Rivas-Limeres V, Grijota-Martínez C, et al. Temperature modulates systemic and central actions of thyroid hormones on BAT thermogenesis. Front Physiol. 2022;13:1017381.

    Article  PubMed  PubMed Central  Google Scholar 

  179. Silva JE, Bianco SDC. Thyroid-adrenergic interactions: physiological and clinical implications. Thyroid. 2008;18(2):157–65.

    Article  CAS  PubMed  Google Scholar 

  180. Branco M, Ribeiro M, Negrão N, Bianco AC. 3,5,3’-Triiodothyronine actively stimulates UCP in brown fat under minimal sympathetic activity. Am J Physiol. 1999;276(1):E179–87.

    CAS  PubMed  Google Scholar 

  181. Yau WW, Yen PM. Thermogenesis in adipose tissue activated by thyroid hormone. Int J Mol Sci. 2020;21(8).

  182. •• Yau WW, Singh BK, Lesmana R, et al. Thyroid hormone (T3) stimulates brown adipose tissue activation via mitochondrial biogenesis and MTOR-mediated mitophagy. Autophagy. 2019;15(1):131–50. This study demonstrates that thyroid hormone triiodothyronine (T33) exhibits cell autonomous effects on mitochondrial autophagy, activity, and turnover in BAT, and suggest that T33 or its analogs may have potential beneficial effects on obesity and metabolic diseases.

    Article  CAS  PubMed  Google Scholar 

  183. Lahesmaa M, Orava J, Schalin-Jäntti C, et al. Hyperthyroidism increases brown fat metabolism in humans. J Clin Endocrinol Metab. 2014;99(1):E28–35.

    Article  PubMed  Google Scholar 

  184. Zhao J, Li M, Chen Y, et al. Elevated serum growth differentiation factor 15 levels in hyperthyroid patients. Front Endocrinol. 2018;9:793.

    Article  Google Scholar 

  185. Chrysovergis K, Wang X, Kosak J, et al. NAG-1/GDF-15 prevents obesity by increasing thermogenesis, lipolysis and oxidative metabolism. Int J Obes (Lond). 2014;38(12):1555–64.

    Article  CAS  PubMed  Google Scholar 

  186. •• Jing X, Wu J, Dong C, et al. COVID-19 instigates adipose browning and atrophy through VEGF in small mammals. Nat Metab. 2022;4(12):1674–83. This study suggests that adipose tissue browning induced by COVID-19 contributes to adipose tissue atrophy and weight loss observed during infection.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Di Filippo L, De Lorenzo R, D’Amico M, et al. COVID-19 is associated with clinically significant weight loss and risk of malnutrition, independent of hospitalisation: a post-hoc analysis of a prospective cohort study. Clin Nutr. 2021;40(4):2420–6.

    Article  PubMed  Google Scholar 

  188. Tomasoni D, Italia L, Adamo M, et al. COVID-19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease. Eur J Heart Fail. 2020;22(6):957–66.

    Article  CAS  PubMed  Google Scholar 

  189. Cai Z, Fang L, Jiang Y, et al. Angiotensin II promotes white adipose tissue browning and lipolysis in mice. Oxid Med Cell Longev. 2022;2022:6022601.

    Article  PubMed  PubMed Central  Google Scholar 

  190. Huang SC, Everts B, Ivanova Y, et al. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat Immunol. 2014;15(9):846–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Song Q, Chen Y, Ding Q, et al. mTORC1 inhibition uncouples lipolysis and thermogenesis in white adipose tissue to contribute to alcoholic liver disease. Hepatol Commun. 2023;7(3): e0059.

    Article  PubMed  PubMed Central  Google Scholar 

  192. Das S, Eder S, Schauer S, et al. Adipose triglyceride lipase contributes to cancer-associated cachexia. Science (New York, NY). 2011;333(6039):233–8.

    Article  CAS  Google Scholar 

  193. Silverio R, Lira FS, Oyama LM, et al. Lipases and lipid droplet-associated protein expression in subcutaneous white adipose tissue of cachectic patients with cancer. Lipids Health Dis. 2017;16(1):159.

    Article  PubMed  PubMed Central  Google Scholar 

  194. Steinhoff KG, Krause K, Linder N, et al. Effects of hyperthyroidism on adipose tissue activity and distribution in adults. Thyroid. 2021;31(3):519–27.

    Article  CAS  PubMed  Google Scholar 

  195. Johann K, Cremer AL, Fischer AW, et al. Thyroid-hormone-induced browning of white adipose tissue does not contribute to thermogenesis and glucose consumption. Cell Rep. 2019;27(11).

  196. Ji C, Guo X. The clinical potential of circulating microRNAs in obesity. Nat Rev Endocrinol. 2019;15(12):731–43.

    Article  CAS  PubMed  Google Scholar 

  197. 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.

    Article  CAS  PubMed  Google Scholar 

  198. Hoeke G, Kooijman S, Boon M, Rensen P, Berbée J. Role of brown fat in lipoprotein metabolism and atherosclerosis. Circ Res. 2016;118(1):173–82.

    Article  CAS  PubMed  Google Scholar 

  199. Ying Z, Tramper N, Zhou E, Boon MR, Rensen PCN, Kooijman S. Role of thermogenic adipose tissue in lipid metabolism and atherosclerotic cardiovascular disease: lessons from studies in mice and humans. Cardiovasc Res. 2023;119(4):905–18.

    Article  CAS  PubMed  Google Scholar 

  200. Cypess AM, Weiner LS, Roberts-Toler C, et al. Activation of human brown adipose tissue by a β3-adrenergic receptor agonist. Cell Metab. 2015;21(1):33–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Dehvari N, Sato M, Bokhari MH, et al. The metabolic effects of mirabegron are mediated primarily by β3-adrenoceptors. Pharmacol Res Perspect. 2020;8(5): e00643.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Dąbrowska AM, Dudka J. Mirabegron, a selective β3-adrenergic receptor agonist, as a potential anti-obesity drug. J Clin Med. 2023;12(21).

  203. Finlin BS, Memetimin H, Zhu B, et al. The β3-adrenergic receptor agonist mirabegron improves glucose homeostasis in obese humans. J Clin Investig. 2020;130(5):2319–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. O’Mara AE, Johnson JW, Linderman JD, et al. Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity. J Clin Investig. 2020;130(5):2209–19.

    Article  PubMed  PubMed Central  Google Scholar 

  205. Loh RKC, Formosa MF, Eikelis N, et al. Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans. Diabetologia. 2018;61(1):220–30.

    Article  CAS  PubMed  Google Scholar 

  206. Wu D, Eeda V, Undi RB, et al. A novel peroxisome proliferator-activated receptor gamma ligand improves insulin sensitivity and promotes browning of white adipose tissue in obese mice. Molecular Metabolism. 2021;54: 101363.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Coelho MS, de Lima CL, Royer C, et al. GQ-16, a TZD-derived partial PPARγ agonist, induces the expression of thermogenesis-related genes in brown fat and visceral white fat and decreases visceral adiposity in obese and hyperglycemic mice. PLoS ONE. 2016;11(5): e0154310.

    Article  PubMed  PubMed Central  Google Scholar 

  208. Gutierrez AD, Gao Z, Hamidi V, et al. Anti-diabetic effects of GLP1 analogs are mediated by thermogenic interleukin-6 signaling in adipocytes. Cell Rep Med. 2022;3(11): 100813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Collier JJ, Batdorf HM, Merrifield KL, et al. Pioglitazone reverses markers of islet beta-cell de-differentiation in db/db mice while modulating expression of genes controlling inflammation and browning in white adipose tissue from insulin-resistant mice and humans. Biomedicines. 2021;9(9).

  210. Kuryłowicz A, Puzianowska-Kuźnicka M. Induction of adipose tissue browning as a strategy to combat obesity. Int J Mol Sci. 2020;21(17).

  211. Zuo L, Geng Z, Song X, et al: Browning of mesenteric white adipose tissue in Crohn’s disease: a new pathological change and therapeutic target. J Crohn’s Colitis. 2023.

  212. Jeschke M, Finnerty C, Emdad F, et al. Mild obesity is protective after severe burn injury. Ann Surg. 2013;258(6):1119–29.

    Article  PubMed  Google Scholar 

  213. Jeschke MG. Postburn hypermetabolism: past, present, and future. J Burn Care Res. 2016;37(2):86–96.

    Article  PubMed  Google Scholar 

  214. Ohashi K, Iwatani H, Kihara S, et al. Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice. Arterioscler Thromb Vasc Biol. 2007;27(9):1910–7.

    Article  CAS  PubMed  Google Scholar 

  215. Sweiss N, Sharma K. Adiponectin effects on the kidney. Best Pract Res Clin Endocrinol Metab. 2014;28(1):71–9.

    Article  CAS  PubMed  Google Scholar 

  216. Hui X, Gu P, Zhang J, et al. Adiponectin enhances cold-induced browning of subcutaneous adipose tissue via promoting M2 macrophage proliferation. Cell Metab. 2015;22(2):279–90.

    Article  CAS  PubMed  Google Scholar 

  217. Sun L, Goh HJ, Verma S, et al. Brown adipose tissues mediate the metabolism of branched chain amino acids during the transitioning from hyperthyroidism to euthyroidism (TRIBUTE). Sci Rep. 2022;12(1):3693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Sun L, Goh HJ, Verma S, et al. Metabolic effects of brown fat in transitioning from hyperthyroidism to euthyroidism. Eur J Endocrinol. 2021;185(4):553–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was sponsored by the National Natural Science Foundation of China (Grant Numbers: 82300489, 82130012, and 81830010), the Shanghai Pujiang Program (No. 23PJD084), the Nurture projects for basic research of Shanghai Chest Hospital (Grant Number: 2022YNJCQ03), and the Innovative Research Team of High-level Local Universities in Shanghai (Grand number: SHSMU-ZLCX20212302).

Author information

Author notes

  1. Yunwen Hu, Yijie Huang, and Yangjing Jiang contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China

    Yunwen Hu, Yijie Huang, Yangjing Jiang, Lvkan Weng, Zhaohua Cai & Ben He

Authors
  1. Yunwen Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yijie Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yangjing Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lvkan Weng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhaohua Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ben He
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.H., Y.H., Y.J., and Z.C. did the majority of the literature searches and created the initial draft, including its organization. Z.C. conceived the work. L.V., Z.C., and B.H. revised and edited the manuscript. All authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Lvkan Weng, Zhaohua Cai or Ben He.

Ethics declarations

Conflict of Interest

The authors have no relevant financial or non-financial interests to disclose.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, Y., Huang, Y., Jiang, Y. et al. The Different Shades of Thermogenic Adipose Tissue. Curr Obes Rep (2024). https://doi.org/10.1007/s13679-024-00559-y

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13679-024-00559-y

Keywords

Search

Navigation