Dexamethasone Inhibits White Adipose Tissue Browning

GIORDANO, ALEJANDRA P.; GAMBARO SABRINA ELIANA; ALZAMENDI, A; HARNICHAR EZEQUIEL; REY, MARÍA AMANDA; ONGARO, L; SPINEDI, EDUARDO; ZUBIRIA GUILLERMINA; GIOVAMBATTISTA , ANDRÉS

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2024 vol. 25

1422-0067

first_pagesettingsOrder Article ReprintsOpen AccessArticleDexamethasone Inhibits White Adipose Tissue Browningby Alejandra Paula Giordano 1,2,Sabrina Eliana Gambaro 1,2,Ana Alzamendi 1,Alejandro Ezequiel Harnichar 1ORCID,María Amanda Rey 1,Luisina Ongaro 3,Eduardo Spinedi 4,María Guillermina Zubiría 1,2 andAndrés Giovambattista 1,2,*1Neuroendocrinology Laboratory, Multidisciplinary Institute of Cellular Biology (IMBICE, CICPBA-CONICET-UNLP), La Plata 1900, Argentina2Biology Department, School of Exact Sciences, Universidad Nacional de La Plata, La Plata 1900, Argentina3Department of Pharmacology and Therapeutics, McGill University, Montréal, QC H3A 0G4, Canada4CENEXA (UNLP-CONICET), La Plata Medical School-UNLP, Calles 60 y 120, La Plata 1900, Argentina*Author to whom correspondence should be addressed.Int. J. Mol. Sci. 2024, 25(5), 2714; https://doi.org/10.3390/ijms25052714Submission received: 20 December 2023 / Revised: 20 February 2024 / Accepted: 24 February 2024 / Published: 27 February 2024(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)Downloadkeyboard_arrow_down Browse Figures Versions NotesAbstractWhite adipose tissue (WAT) regulates energy balance through energy storage, adipokines secretion and the thermogenesis process. Beige adipocytes are responsible for WAT thermogenesis. They are generated by adipogenesis or transdifferentiation during cold or β3-adrenergic agonist stimulus through a process called browning. Browning has gained significant interest for to its preventive effect on obesity. Glucocorticoids (GCs) have several functions in WAT biology; however, their role in beige adipocyte generation and WAT browning is not fully understood. The aim of our study was to determine the effect of dexamethasone (DXM) on WAT thermogenesis. For this purpose, rats were treated with DXM at room temperature (RT) or cold conditions to determine different thermogenic markers. Furthermore, the effects of DXM on the adipogenic potential of beige precursors and on mature beige adipocytes were evaluated in vitro. Our results showed that DXM decreased UCP-1 mRNA and protein levels, mainly after cold exposure. In vitro studies showed that DXM decreased the expression of a beige precursor marker (Ebf2), affecting their ability to differentiate into beige adipocytes, and inhibited the thermogenic response of mature beige adipocytes (Ucp-1, Dio2 and Pgc1α gene expressions and mitochondrial respiration). Overall, our data strongly suggest that DXM can inhibit the thermogenic program of both retroperitoneal and inguinal WAT depots, an effect that could be exerted, at least partially, by inhibiting de novo cell generation and the thermogenic response in beige adipocytes.