Brown adipokines are regulatory factors secreted by brown and beige adipocytes that exhibit endocrine, paracrine, and autocrine actions. Peptidic and non-peptidic molecules, including miRNAs and lipids, are constituents of brown adipokines. Brown adipose tissue remodeling to meet thermogenic needs is dependent on the secretory properties of brown/beige adipocytes. The association between brown fat activity and a healthy metabolic profile, in relation to energy balance and glucose and lipid homeostasis, is influenced by the endocrine actions of brown adipokines. A comprehensive knowledge of the brown adipocyte secretome is still lacking. Advancements in the identification and characterization of brown adipokines will facilitate therapeutic interventions for metabolic diseases, as these molecules are obvious candidates to therapeutic agents. Moreover, identification of brown adipokines as circulating biomarkers of brown adipose tissue activity may be particularly useful for noninvasive assessment of brown adipose tissue alterations in human pathologies.
KeywordsAdipokine Beige adipocyte Brown adipocyte Brown adipose tissue
This work has been supported by Grants SAF2017-85722-R from the Ministerio de Ciencia e Innovación (MINECO) and PI17/00420 from the Instituto de Salud Carlos III, Spain, cofinanced by the European Regional Development Fund (ERDF), and Fundació Marató de TV3 (grant 201612-30). M.P. and J.V. are “Juan de la Cierva” researchers (MINECO, Spain).
- Chen KY, Cypess AM, Laughlin MR, Haft CR, Hu HH, Bredella MA et al (2014) Brown adipose reporting criteria in imaging studies (BARCIST 1.0): recommendations for standardized FDG-PET/CT experiments in humans. Cell Metab 24:210–222Google Scholar
- García-Alonso V, Clària J (2014) Prostaglandin E2 signals white-to-brown adipogenic differentiation. Adipocytes 3:290–296Google Scholar
- García-Alonso V, López-Vicario C, Titos E, Morán-Salvador E, González-Périz A, Rius B et al (2013) Coordinate functional regulation between microsomal prostaglandin E synthase-1 (mPGES-1) and peroxisome proliferator activated receptor γ (PPARγ) in the conversion of white-to-brown adipocytes. J Biol Chem 288:28230–28242PubMedPubMedCentralGoogle Scholar
- Jorge AS, Jorge GC, Paraíso AF, Franco RM, Vieira LJ, Hilzenderger AM et al (2017) Brown and White adipose tissue expression of IL6, UCP1 and SIRT1 are associated with alterations in clinical, metabolic and anthropometric parameters in obese humans. Exp Clin Endocrinol Diabetes 125:163–170PubMedGoogle Scholar
- Kang YE, Choung S, Lee JH, Kim HJ, Ku BJ (2017) The role of circulating Slit2, the one of the newly Batokines, in human diabetes mellitus. Endocrinol Metab (Seoul) 32:383–388Google Scholar
- Kralisch S, Hoffmann A, Kratzsch J, Blüher M, Stumvoll M, Fasshauer M et al (2017) The brown-fat-secreted adipokine neuregulin 4 is decreased in gestational diabetes mellitus. Diabetes Metab. pii: S1262-3636(17)30465-2Google Scholar
- Orava J, Nuutila P, Lidell ME, Oikonen V, Noponen T, Viljanen T et al (2011) Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab 14:272–279Google Scholar
- Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J (2010) Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem 285:7153–7164PubMedGoogle Scholar
- Stanford KI, Middelbeek RJ, Townsend KL, An D, Nygaard EB, Hitchcox KM et al (2016) AgRP neurons control systemic insulin sensitivity via myostatin expression in brown adipose tissue. Cell 165:125–138Google Scholar