Dexamethasone Inhibits White Adipose Tissue Browning

GIORDANO AP; GAMBARO S; ALZAMENDI A; HAMICHAR AE; REY, MARÍA AMANDA; ONGARO L; SPINEDI E; ZUBIRÍA, M.G.; GIOVAMBATTISTA A

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Año: 2024 vol. 25

1422-0067

White 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 Citation: Giordano, A.P.; Gambaro, S.E.; Alzamendi, A.; Harnichar, A.E.; Rey, M.A.; Ongaro, L.; Spinedi, E.; Zubiría, M.G.; Giovambattista, A. Dexamethasone Inhibits White Adipose Tissue Browning. Int. J. Mol. Sci. 2024, 25, 2714. https://doi.org/ 10.3390/ijms25052714 Academic Editor: Alina Kuryłowicz Received: 20 December 2023 Revised: 20 February 2024 Accepted: 24 February 2024 Published: 27 February 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). decreased UCP-1 mRNA and protein levels, mainly after cold exposure. In vitro studies showed that DXMdecreasedtheexpressionofabeigeprecursormarker(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 DXMcaninhibit 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