Dexamethasone Inhibits White Adipose Tissue Browning

GIORDANO, ALEJANDRA P.; GAMBARO, S.E.; ALZAMENDI, A.; HARNICHAR, ALEJANDRO E.; REY, MARÍA AMANDA; ONGARO, LUISINA; SPINEDI, E.; ZUBIRÍA, MARÍA GUILLERMINA; GIOVAMBATTISTA, A.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2024 vol. 25

1422-0067

Abstract: White adipose tissue (WAT) regulates energy balance through energy storage, adipokinessecretion and the thermogenesis process. Beige adipocytes are responsible forWAT thermogenesis.They are generated by adipogenesis or transdifferentiation during cold or β3-adrenergic agoniststimulus through a process called browning. Browning has gained significant interest for to itspreventive 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 ofour study was to determine the effect of dexamethasone (DXM) on WAT thermogenesis. For thispurpose, rats were treated with DXM at room temperature (RT) or cold conditions to determinedifferent thermogenic markers. Furthermore, the effects of DXM on the adipogenic potential of beigeprecursors and on mature beige adipocytes were evaluated in vitro. Our results showed that DXMdecreased UCP-1 mRNA and protein levels, mainly after cold exposure. In vitro studies showed thatDXM decreased the expression of a beige precursor marker (Ebf2), affecting their ability to differentiateinto beige adipocytes, and inhibited the thermogenic response of mature beige adipocytes (Ucp-1, Dio2and Pgc1α gene expressions and mitochondrial respiration). Overall, our data strongly suggest thatDXM can inhibit the thermogenic program of both retroperitoneal and inguinalWAT depots, an effectthat could be exerted, at least partially, by inhibiting de novo cell generation and the thermogenicresponse in beige adipocytes.