The endocrine role of brown adipose tissue: An update on actors and actions.
Journal
Reviews in endocrine & metabolic disorders
ISSN: 1573-2606
Titre abrégé: Rev Endocr Metab Disord
Pays: Germany
ID NLM: 100940588
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
accepted:
26
02
2021
pubmed:
14
3
2021
medline:
15
3
2022
entrez:
13
3
2021
Statut:
ppublish
Résumé
In recent years, brown adipose tissue (BAT) has been recognized not only as a main site of non-shivering thermogenesis in mammals, but also as an endocrine organ. BAT secretes a myriad of regulatory factors. These so-called batokines exert local autocrine and paracrine effects, as well as endocrine actions targeting tissues and organs at a distance. The endocrine batokines include peptide factors, such as fibroblast growth factor-21 (FGF21), neuregulin-4 (NRG4), phospholipid transfer protein (PLTP), interleukin-6, adiponectin and myostatin, and also lipids (lipokines; e.g., 12,13-dihydroxy-9Z-octadecenoic acid [12,13-diHOME]) and miRNAs (e.g., miR-99b). The liver, heart, and skeletal muscle are the most commonly reported targets of batokines. In response to BAT thermogenic activation, batokines such as NRG4 and PLTP are released and act to reduce hepatic steatosis and improve insulin sensitivity. Stress-induced interleukin-6-mediated signaling from BAT to liver favors hepatic glucose production through enhanced gluconeogenesis. Batokines may act on liver to induce the secretion of regulatory hepatokines (e.g. FGF21 and bile acids in response to miR-99b and PLTP, respectively), thereby resulting in a systemic expansion of BAT-originating signals. Batokines also target extrahepatic tissues: FGF21 and 12,13-diHOME are cardioprotective, whereas BAT-secreted myostatin and 12,13-diHOME influence skeletal muscle development and performance. Further research is needed to ascertain in humans the role of batokines, which have been identified mostly in experimental models. The endocrine role of BAT may explain the association between active BAT and a healthy metabolism in the human system, which is characterized by small amounts of BAT and a likely moderate BAT-mediated energy expenditure.
Identifiants
pubmed: 33712997
doi: 10.1007/s11154-021-09640-6
pii: 10.1007/s11154-021-09640-6
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
31-41Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Cannon B. Nedergaard J Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84:277–359.
pubmed: 14715917
Ikeda K, Maretich P, Kajimura S. The Common and Distinct Features of Brown and Beige Adipocytes. Trends Endocrinol Metab. 2018;29:191–200.
pubmed: 29366777
pmcid: 5826798
Rasmussen AT. The glandular status of multilocular brown adipose tissue. Endocrinology. 1922;6:760–70.
Betz MJ, Enerbäck S. Human Brown Adipose Tissue: What We Have Learned So Far. Diabetes. 2015;64:2352–60.
pubmed: 26050667
Villarroya F, Cereijo R, Villarroya J, Giralt M. Brown adipose tissue as a secretory organ. Nat Rev Endocrinol. 2017;13:26–35.
pubmed: 27616452
Villarroya F, Gavaldà-Navarro A, Peyrou M, Villarroya J, Giralt M. The lives and times of brown adipokines. Trends Endocrinol Metab. 2017;28:855–67.
pubmed: 29113711
Villarroya J, Cereijo R, Gavaldà-Navarro A, Peyrou M, Giralt M, Villarroya F. New insights into the secretory functions of brown adipose tissue. J Endocrinol. 2019;243:R19–27.
pubmed: 31419785
White A, Levine R. History of Hormones. In: Goldberger RF, Yamamoto KR, editors. Biological Regulation and Development. New York: Springer Science+Business Media; 1982. p. 1–24.
Horwitz BA, Inokuchi T, Moore BJ, Stern JS. The effect of brown fat removal on the development of obesity in Zucker and Osborne-Mendel rats. Int J Obes. 1985;9(Suppl 2):43–8.
pubmed: 3840775
Rothwell NJ, Stock MJ. Surgical removal of brown fat results in rapid and complete compensation by other depots. Am J Physiol. 1989;257:R253-258.
pubmed: 2548406
Grunewald ZI, Winn NC, Gastecki ML, Woodford ML, Ball JR, Hansen SA, Sacks HS, Vieira-Potter VJ, Padilla J. Removal of interscapular brown adipose tissue increases aortic stiffness despite normal systemic glucose metabolism in mice. Am J Physiol Regul Integr Comp Physiol. 2018;314:R584-R597.
Stern JS, Inokuchi T, Castonguay TW, Wickler SJ, Horwitz BA. Scapular brown fat removal enhances development of adiposity in cold-exposed obese Zucker rats. Am J Physiol. 1984;247:R918–26.
pubmed: 6496775
Moore BJ, Inokuchi T, Stern JS, Horwitz BA. Brown adipose tissue lipectomy leads to increased fat deposition in Osborne-Mendel rats. Am J Physiol. 1985;248:R231–5.
pubmed: 3970238
Kong X, Yao T, Zhou P, Kazak L, Tenen D, Lyubetskaya A, Dawes BA, Tsai L, Kahn BB, Spiegelman BM, Liu T, Rosen ED. Brown adipose tissue controls skeletal muscle function via the secretion of myostatin. Cell Metab. 2018;28:631–43.
pubmed: 30078553
pmcid: 6170693
Stanford KI, Lynes MD, Takahashi H, Baer LA, Arts PJ, May FJ, Lehnig AC, Middelbeek RJW, Richard JJ, So K, Chen EY, Gao F, Narain NR, Distefano G, Shettigar VK, Hirshman MF, Ziolo MT, Kiebish MA, Tseng YH, Coen PM, Goodyear LJ. 12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake. Cell Metab. 2018;27:1111–20.
pubmed: 29719226
pmcid: 5935136
Lowell BB, Susulic V, Hamann A, Lawitts JA, Himms-Hagen J, Boyer BB, Kozak LP, Flier JS. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature. 1993;366:740–2.
pubmed: 8264795
Enerback S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper M-E, Kozak LP. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature. 1997;387:90–4.
pubmed: 9139827
Wang Y, Paulo E, Wu D, Wu Y, Huang W, Chawla A, Wang B. Adipocyte Liver Kinase b1 Suppresses Beige Adipocyte Renaissance Through Class IIa Histone Deacetylase 4. Diabetes. 2017;66:2952–63.
pubmed: 28882900
pmcid: 5697944
Villarroya F, Giralt M. The beneficial effects of brown fat transplantation: further evidence of an endocrine role of brown adipose tissue. Endocrinology. 2015;156:2368–70.
pubmed: 26091427
White JD, Dewal RS, Stanford KI. The beneficial effects of brown adipose tissue transplantation. Mol Aspects Med. 2019;68:74–81.
pubmed: 31228478
pmcid: 6708446
Gunawardana SC. Therapeutic value of brown adipose tissue: Correcting metabolic disease through generating healthy fat. Adipocyte. 2012;1:250–5.
pubmed: 23700541
pmcid: 3609108
Payab M, Abedi M, Foroughi Heravani N, Hadavandkhani M, Arabi M, Tayanloo-Beik A, Sheikh Hosseini M, Gerami H, Khatami F, Larijani B, Abdollahi M, Arjmand B. Brown adipose tissue transplantation as a novel alternative to obesity treatment: a systematic review. Int J Obes (Lond). 2021;45:109–21.
Yuan X, Hu T, Zhao H, Huang Y, Ye R, Lin J, Zhang C, Zhang H, Wei G, Zhou H, Dong M, Zhao J, Wang H, Liu Q, Lee HJ, Jin W, Chen ZJ. Brown adipose tissue transplantation ameliorates polycystic ovary syndrome. Proc Natl Acad Sci U S A. 2016;113:2708–13.
pubmed: 26903641
pmcid: 4790997
Du L, Wang Y, Li CR, Chen LJ, Cai JY, Xia ZR, Zeng WT, Wang ZB, Chen XC, Hu F, Zhang D, Xing XW, Yang ZX. Rat BAT xenotransplantation recovers the fertility and metabolic health of PCOS mice. J Endocrinol. 2020 Dec 1:JOE-20–0068.R1. https://doi.org/10.1530/JOE-20-0068 . Online ahead of print.
Thomou T, Mori MA, Dreyfuss JM, Konishi M, Sakaguchi M, Wolfrum C, Rao TN, Winnay JN, Garcia-Martin R, Grinspoon SK, Gorden P, Kahn CR. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 2017;542:450–5.
pubmed: 28199304
pmcid: 5330251
Pinckard KM, Shettigar VK, Wright KR, Abay E, Baer LA, Vidal P, Dewal RS, Das D, Duarte-Sanmiguel S, Hernández-Saavedra D, Arts PJ, Lehnig AC, Bussberg V, Narain NR, Kiebish MA, Yi F, Sparks LM, Goodpaster BH, Smith SR, Pratley RE, Lewandowski ED, Raman SV, Wold LE, Gallego-Perez D, Coen PM, Ziolo MT, Stanford K. A Novel Endocrine Role the BAT-Released Lipokine 12,13-diHOME to Mediate Cardiac Function. Circulation. 2021;143:145–59.
pubmed: 33106031
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;286:12983–90.
pubmed: 21317437
pmcid: 3075644
Giralt M, Gavaldà-Navarro A, Villarroya F. Fibroblast growth factor-21, energy balance and obesity. Mol Cell Endocrinol. 2015;418(Pt 1):66–73.
pubmed: 26415590
Zarei M, Pizarro-Delgado J, Barroso E, Palomer X, Vázquez-Carrera M. Targeting FGF21 for the Treatment of Nonalcoholic Steatohepatitis. Trends Pharmacol Sci. 2020;41:199–208.
pubmed: 31980251
Kliewer SA, Mangelsdorf DJ. A Dozen Years of Discovery: Insights into the Physiology and Pharmacology of FGF21. Cell Metab. 2019;29:246–53.
pubmed: 30726758
pmcid: 6368396
Markan KR, Naber MC, Ameka MK, Anderegg MD, Mangelsdorf DJ, Kliewer SA, Mohammadi M, Potthoff MJ. Circulating FGF21 is liver derived and enhances glucose uptake during refeeding and overfeeding. Diabetes. 2014;63:4057–63.
pubmed: 25008183
pmcid: 4238010
Stanford KI, Middelbeek RJ, Townsend KL, An D, Nygaard EB, Hitchcox KM, Markan KR, Nakano K, Hirshman MF, Tseng YH, Goodyear LJ. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest. 2013;123:215–23.
pubmed: 23221344
Keipert S, Kutschke M, Lamp D, Brachthäuser L, Neff F, Meyer CW, Oelkrug R, Kharitonenkov A, Jastroch M. Genetic disruption of uncoupling protein 1 in mice renders brown adipose tissue a significant source of FGF21 secretion. Mol Metab. 2015;4:537–42.
pubmed: 26137441
pmcid: 4481421
Wang GX, Zhao XY, Meng ZX, Kern M, Dietrich A, Chen Z, Cozacov Z, Zhou D, Okunade AL, Su X, Li S, Blüher M, Lin JD. The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med. 2014;20:1436–1443.
Christian M. Transcriptional fingerprinting of “browning” white fat identifies NRG4 as a novel adipokine. Adipocyte. 2014;4:50–4.
pubmed: 26167402
pmcid: 4496975
Chen Y, Buyel JJ, Hanssen MJ, Siegel F, Pan R, Naumann J, Schell M, van der Lans A, Schlein C, Froehlich H, Heeren J, Virtanen KA, van Marken LW, Pfeifer A. Exosomal microRNA miR-92a concentration in serum reflects human brown fat activity. Nat Commun. 2016;7:11420.
pubmed: 27117818
pmcid: 4853423
Sponton CH, Hosono T, Taura J, Jedrychowski MP, Yoneshiro T, Wang Q, Takahashi M, Matsui Y, Ikeda K, Oguri Y, Tajima K, Shinoda K, Pradhan RN, Chen Y, Brown Z, Roberts LS, Ward CC, Taoka H, Yokoyama Y, Watanabe M, Karasawa H, Nomura DK, Kajimura S. The regulation of glucose and lipid homeostasis via PLTP as a mediator of BAT-liver communication. EMBO Rep. 2020;21:e49828.
pubmed: 32672883
pmcid: 7507062
Qing H, Desrouleaux R, Israni-Winger K, Mineur YS, Fogelman N, Zhang C, Rashed S, Palm NW, Sinha R, Picciotto MR, Perry RJ, Wang A. Origin and Function of Stress-Induced IL-6 in Murine Models. Cell. 2020;182:372–87.
pubmed: 32610084
pmcid: 7384974
Burýsek L, Houstek J. beta-Adrenergic stimulation of interleukin-1alpha and interleukin-6 expression in mouse brown adipocytes. FEBS Lett. 1997;411:83–6.
pubmed: 9247147
Mauer J, Chaurasia B, Goldau J, Vogt MC, Ruud J, Nguyen KD, Theurich S, Hausen AC, Schmitz J, Brönneke HS, Estevez E, Allen TL, Mesaros A, Partridge L, Febbraio MA, Chawla A, Wunderlich FT, Brüning JC. Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nat Immunol. 2014;15:423–30.
pubmed: 24681566
pmcid: 4161471
Villarroya F, Cereijo R, Villarroya J, Gavaldà-Navarro A, Giralt M. Toward an Understanding of How Immune Cells Control Brown and Beige Adipobiology. Cell Metab. 2018;27:954–961.
Shen H, Jiang L, Lin JD, Omary MB, Rui L. Brown fat activation mitigates alcohol-induced liver steatosis and injury in mice. J Clin Invest. 2019;129:2305–17.
pubmed: 30888335
pmcid: 6546460
Min SY, Kady J, Nam M, Rojas-Rodriguez R, Berkenwald A, Kim JH, Noh HL, Kim JK, Cooper MP, Fitzgibbons T, Brehm MA, Corvera S. Human “brite/beige” adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice. Nat Med. 2016;22:312–8.
pubmed: 26808348
pmcid: 4777633
Liu D, Li Y, Shang Y, Wang W, Chen SZ. Effect of brown adipose tissue/cells on the growth of mouse hepatocellular carcinoma in vitro and in vivo. Oncol Lett. 2019;17:3203–10.
pubmed: 30867750
pmcid: 6396209
Yilmaz Y, Ones T, Purnak T, Ozguven S, Kurt R, Atug O, Turoglu HT, Imeryuz N. Association between the presence of brown adipose tissue and non-alcoholic fatty liver disease in adult humans. Aliment Pharmacol Ther. 2011;34:318–323.
Duncan JG, Fong JL, Medeiros DM, Finck BN, Kelly DP. Insulin-resistant heart exhibits a mitochondrial biogenic response driven by the peroxisome proliferator-activated receptor-alpha/PGC-1alpha gene regulatory pathway. Circulation. 2007;115:909–17.
pubmed: 17261654
pmcid: 4322937
Ilkun O, Wilde N, Tuinei J, Pires KM, Zhu Y, Bugger H, Soto J, Wayment B, Olsen C, Litwin SE, Abel DE. Antioxidant treatment normalizes mitochondrial energetics and myocardial insulin sensitivity independently of changes in systemic metabolic homeostasis in a mouse model of the metabolic syndrome. J Mol Cell Cardiol. 2015;85:104–16.
pubmed: 26004364
pmcid: 4530070
Thoonen R, Ernande L, Cheng J, Nagasaka Y, Yao V, Miranda-Bezerra A, Chen C, Chao W, Panagia M, Sosnovik DE, Puppala D, Armoundas AA, Hindle A, Bloch KD, Buys ES, Scherrer-Crosbie M. Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy. J Mol Cell Cardiol. 2015;84:202–11.
pubmed: 25968336
pmcid: 4470477
Zhou X, Li Z, Qi M, Zhao P, Duan Y, Yang G, Yuan L. Brown adipose tissue-derived exosomes mitigate the metabolic syndrome in high fat diet mice. Theranostics. 2020;10:8197–210.
pubmed: 32724466
pmcid: 7381731
Planavila A, Redondo I, Hondares E, Vinciguerra M, Munts C, Iglesias R, Gabrielli LA, Sitges M, Giralt M, van Bilsen M, Villarroya F. Fibroblast growth factor 21 protects against cardiac hypertrophy in mice. Nat Commun. 2013;4:2019.
pubmed: 23771152
Ruan CC, Kong LR, Chen XH, Ma Y, Pan XX, Zhang ZB, Gao PJ. A2A receptor activation attenuates hypertensive cardiac remodeling via promoting brown adipose tissue-derived FGF21. Cell Metab. 2018;28:476–89.
pubmed: 30017353
Iacobellis G, Bianco AC. Epicardial adipose tissue: emerging physiological, pathophysiological and clinical features. Trends Endocrinol Metab. 2011;22:450–7.
pubmed: 21852149
pmcid: 4978122
Chechi K, Vijay J, Voisine P, Mathieu P, Bossé Y, Tchernof A, Grundberg E, Richard D. UCP1 expression-associated gene signatures of human epicardial adipose tissue. JCI Insight. 2019;4:e123618.
pmcid: 6538324
Rodriguez J, Vernus B, Chelh I, Cassar-Malek I, Gabillard JC, Hadj Sassi A, Seiliez I, Picard B, Bonnieu A. Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cell Mol Life Sci. 2014;71:4361–71.
pubmed: 25080109
Shan T, Liang X, Bi P, Kuang S. Myostatin knockout drives browning of white adipose tissue through activating the AMPK-PGC1α-Fndc5 pathway in muscle. FASEB J. 2013;27:1981–9.
pubmed: 23362117
pmcid: 3633817
Steculorum SM, Ruud J, Karakasilioti I, Backes H, Engström Ruud L, Timper K, Hess ME, Tsaousidou E, Mauer J, Vogt MC, Paeger L, Bremser S, Klein AC, Morgan DA, Frommolt P, Brinkkötter PT, Hammerschmidt P, Benzing T, Rahmouni K, Wunderlich FT, Kloppenburg P, Brüning JC. AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue. Cell. 2016;165:125–38.
pubmed: 27015310
pmcid: 5157157
Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Boström EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Højlund K, Gygi SP, Spiegelman BM. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481:463–8.
pubmed: 22237023
pmcid: 3522098
Cereijo R, Gavaldà-Navarro A, Cairó M, Quesada-López T, Villarroya J, Morón-Ros S, Sánchez-Infantes D, Peyrou M, Iglesias R, Mampel T, Turatsinze JV, Eizirik DL, Giralt M, Villarroya F. CXCL14, a Brown Adipokine that Mediates Brown-Fat-to-Macrophage Communication in Thermogenic Adaptation. Cell Metab. 2018;28:750–63.
pubmed: 30122557
Campderros L, Moure R, Cairó M, Gavaldà-Navarro A, Quesada-López T, Cereijo R, Giralt M, Villarroya J, Villarroya F. Brown adipocytes secrete GDF15 in response to thermogenic activation. Obesity (Silver Spring). 2019;27:1606–16.
Villarroya F, Cereijo R, Gavaldà-Navarro A, Villarroya J, Giralt M. Inflammation of brown/beige adipose tissues in obesity and metabolic disease. J Intern Med. 2018;284:492–504.
pubmed: 29923291
Henningsen JB, Scheele C. Brown Adipose Tissue: A Metabolic Regulator in a Hypothalamic Cross Talk? Annu Rev Physiol. 2021;83:279–301.
pubmed: 33158377
Néchad M, Ruka E, Thibault J. Production of nerve growth factor by brown fat in culture: relation with the in vivo developmental stage of the tissue. Comp Biochem Physiol Comp Physiol. 1994;107:381–8.
pubmed: 7907965
Nisoli E, Tonello C, Benarese M, Liberini P, Carruba MO. Expression of nerve growth factor in brown adipose tissue: implications for thermogenesis and obesity. Endocrinology. 1996;137:495–503.
pubmed: 8593794
Hu B, Jin C, Zeng X, Resch JM, Jedrychowski MP, Yang Z, Desai BN, Banks AS, Lowell BB, Mathis D, Spiegelman BM. γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis. Nature. 2020;578:610–4.
pubmed: 32076265
pmcid: 7055484
Zeng X, Ye M, Resch JM, Jedrychowski MP, Hu B, Lowell BB, Ginty DD, Spiegelman BM. Innervation of thermogenic adipose tissue via a calsyntenin 3beta-S100b axis. Nature. 2019;569:229–35.
pubmed: 31043739
pmcid: 6589139
Becher T, Palanisamy S, Kramer DJ, Eljalby M, Marx SJ, Wibmer AG, Butler SD, Jiang CS, Vaughan R, Schöder H, Mark A, Cohen P. Brown adipose tissue is associated with cardiometabolic health. Nat Med. 2021;27:58–65.
pubmed: 33398160
pmcid: 8461455
Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, Lo JC, Zeng X, Ye L, Khandekar MJ, Wu J, Gunawardana SC, Banks AS, Camporez JP, Jurczak MJ, Kajimura S, Piston DW, Mathis D, Cinti S, Shulman GI, Seale P, Spiegelman BM. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 2014;156:304–316.
Becher, Palanisamy S, Kramer DJ, Marx SJ, Wibmer AG, Del Gaudio I, Butler SD, Jiang CS, Vaughan R, Schöder H, Di Lorenzo A, Mark A, Cohen P. Brown Adipose Tissue is Associated with Improved Cardiometabolic Health and Regulates Blood Pressure. bioRxiv 2020;53351880. https://doi.org/10.1101/2020.02.08.933754 .
Fitzgibbons TP, Kogan S, Aouadi M, Hendricks GM, Straubhaar J, Czech MP. Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation. Am J Physiol Heart Circ Physiol. 2011;301:H1425–37.
pubmed: 21765057
pmcid: 3197360
Tonello C, Giordano A, Cozzi V, Cinti S, Stock MJ, Carruba MO, Nisoli E. Role of sympathetic activity in controlling the expression of vascular endothelial growth factor in brown fat cells of lean and genetically obese rats. FEBS Lett. 1999;442:167–72.
pubmed: 9928995
Sun K, Kusminski CM, Luby-Phelps K, Spurgin SB, An YA, Wang QA, Holland WL, Scherer PE. Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure. Mol Metab. 2014;3:474–83.
pubmed: 24944907
pmcid: 4060212
Pellegrinelli V, Peirce VJ, Howard L, S, Türei D, Senzacqua M, Frontini A, Dalley JW, Horton AR, Bidault G, Severi I, Whittle A, Rahmouni K, Saez-Rodriguez J, Cinti S, Davies AM, Vidal-Puig A. Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue. Nat Commun. 2018;9:4974.
Wang CH, Lundh M, Fu A, Kriszt R, Huang TL, Lynes MD, Leiria LO, Shamsi F, Darcy J, Greenwood BP, Narain NR, Tolstikov V, Smith KL, Emanuelli B, Chang YT, Hagen S, Danial NN, Kiebish MA, Tseng YH. CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice. Sci Transl Med. 2020;12(558):eaaz8664
Deshmukh AS, Peijs L, Beaudry JL, Jespersen NZ, Nielsen CH, Ma T, Brunner AD, Larsen TJ, Bayarri-Olmos R, Prabhakar BS, Helgstrand C, Severinsen MCK, Holst B, Kjaer A, Tang-Christensen M, Sanfridson A, Garred P, Privé GG, Pedersen BK, Gerhart-Hines Z, Nielsen S, Drucker DJ, Mann M, Scheele C. Proteomics-Based Comparative Mapping of the Secretomes of Human Brown and White Adipocytes Reveals EPDR1 as a Novel Batokine. Cell Metab. 2019;30:963–75.
pubmed: 31668873
Hondares E, Gallego-Escuredo JM, Flachs P, Frontini A, Cereijo R, Goday A, Perugini J, Kopecky P, Giralt M, Cinti S, Kopecky J, Villarroya F. Fibroblast growth factor-21 is expressed in neonatal and pheochromocytoma-induced adult human brown adipose tissue. Metabolism. 2014;63:312–7.
pubmed: 24369918
Tutunchi H, Ostadrahimi A, Hosseinzadeh-Attar MJ, Miryan M, Mobasseri M, Ebrahimi-Mameghani M. A systematic review of the association of neuregulin 4, a brown fat-enriched secreted factor, with obesity and related metabolic disturbances. Obes Rev. 2020;21(2):e12952
Sookoian S, Pirola CJ. Nonalcoholic Fatty Liver Disease Progresses into Severe NASH when Physiological Mechanisms of Tissue Homeostasis Collapse. Ann Hepatol. 2018;17:182–186.
Chen LL, Peng MM, Zhang JY, Hu X, Min J, Huang QL, Wan LM. Elevated circulating Neuregulin4 level in patients with diabetes. Diabetes Metab Res Rev. 2017;33(4).
Vasan SK, Noordam R, Gowri MS, Neville MJ, Karpe F, Christodoulides C. The proposed systemic thermogenic metabolites succinate and 12,13-diHOME are inversely associated with adiposity and related metabolic traits: evidence from a large human cross-sectional study. Diabetologia. 2019;62:2079–87.
pubmed: 31309263
pmcid: 6805813
R Cereijo T Quesada-López A Gavaldà-Navarro J Tarasco S Pellitero M Reyes M Puig-Domingo M Giralt D Sanchez-Infantes F Villarroya 2020 The chemokine CXCL14 is negatively associated with obesity and concomitant type 2 diabetes in humans. Int J Obes 2021. https://doi.org/10.1038/s41366-020-00732-y .
Cereijo R, Taxerås SD, Piquer-Garcia I, Pellitero S, Martínez E, Tarascó J, Moreno P, Balibrea J, Puig-Domingo M, Jiménez-Pavón D, Lerin C, Villarroya F, Sánchez-Infantes D. Elevated Levels of Circulating miR-92a Are Associated with Impaired Glucose Homeostasis in Patients with Obesity and Correlate with Metabolic Status After Bariatric Surgery. Obes Surg. 2020;30:174–9.
pubmed: 31346930
Lidell ME. Brown Adipose Tissue in Human Infants. Handb Exp Pharmacol. 2019;251:107–23.
pubmed: 29675580
Sánchez-Infantes D, Gallego-Escuredo JM, Díaz M, Aragonés G, Sebastiani G, López-Bermejo A, de Zegher F, Domingo P, Villarroya F, Ibáñez L. Circulating FGF19 and FGF21 surge in early infancy from infra- to supra-adult concentrations. Int J Obes (Lond). 2015;39:742–6.
Whittle AJ, Carobbio S, Martins L, Slawik M, Hondares E, Vázquez MJ, Morgan D, Csikasz RI, Gallego R, Rodriguez-Cuenca S, Dale M, Virtue S, Villarroya F, Cannon B, Rahmouni K, López M, Vidal-Puig A. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell. 2012;149:871–85.
pubmed: 22579288
pmcid: 3383997
Heaton JM. The distribution of brown adipose tissue in the human. J Anat. 1972;112(Pt 1):35–9.
pubmed: 5086212
pmcid: 1271341
Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360:1509–17.
pubmed: 19357406
pmcid: 2859951
Steinberg JD, Vogel W, Vegt E. Factors influencing brown fat activation in FDG PET/CT: a retrospective analysis of 15,000+ cases. Br J Radiol. 90:20170093
Adamczak M, Rzepka E, Chudek J, Wiecek A. Ageing and plasma adiponectin concentration in apparently healthy males and females. Clin Endocrinol (Oxf). 2005;62:114–8.
Hanks LJ, Gutiérrez OM, Bamman MM, Ashraf A, McCormick KL, Casazza K. Circulating levels of fibroblast growth factor-21 increase with age independently of body composition indices among healthy individuals. J Clin Transl Endocrinol. 2015;2:77–82
Villarroya J, Gallego-Escuredo JM, Delgado-Anglés A, Cairó M, Moure R, Gracia Mateo M, Domingo JC, Domingo P, Giralt M, Villarroya F. Aging is associated with increased FGF21 levels but unaltered FGF21 responsiveness in adipose tissue. Aging Cell. 2018;17:e12822.
pubmed: 30043445
pmcid: 6156525
Petruzzelli M, Schweiger M, Schreiber R, Campos-Olivas R, Tsoli M, Allen J, Swarbrick M, Rose-John S, Rincon M, Robertson G, Zechner R, Wagner EF. A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab. 2014;20:433–447.
Abdullahi A, Samadi O, Auger C, Kanagalingam T, Boehning D, Bi S, Jeschke MG. Browning of white adipose tissue after a burn injury promotes hepatic steatosis and dysfunction. Cell Death Dis. 2019;10:870.
pubmed: 31740668
pmcid: 6861318
Moulder R, Bhosale SD, Goodlett DR, Lahesmaa R. Analysis of the plasma proteome using iTRAQ and TMT-based Isobaric labeling. Mass Spectrom Rev. 2018;37:583–606.
pubmed: 29120501
Armingol E, Officer A, Harismendy O, Lewis NE. Deciphering cell-cell interactions and communication from gene expression. Nat Rev Genet. 2020;9:1–18.