Glutathione Decrement Drives Thermogenic Program in Adipose Cells

Daniele Lettieri Barbato, Giuseppe Tatulli, Stefano Maria Cannata, Sergio Bernardini, Katia Aquilano, Maria R. Ciriolo

Research output: Contribution to journalArticle

Abstract

Adipose tissue metabolically adapts to external stimuli. We demonstrate that the induction of the thermogenic program in white adipocytes, through cold exposure in mice or in vitro adrenergic stimulation, is accompanied by a decrease in the intracellular content of glutathione (GSH). Moreover, the treatment with a GSH depleting agent, buthionine sulfoximine (BSO), recapitulates the effect of cold exposure resulting in the induction of thermogenic program. In particular, BSO treatment leads to enhanced uncoupling respiration as demonstrated by increased expression of thermogenic genes (e.g. Ucp1, Ppargc1a), augmented oxygen consumption and decreased mitochondrial transmembrane potential. Buffering GSH decrement by pre-treatment with GSH ester prevents the up-regulation of typical markers of uncoupling respiration. We demonstrate that FoxO1 activation is responsible for the conversion of white adipocytes into a brown phenotype as the "browning" effects of BSO are completely abrogated in cells down-regulating FoxO1. In mice, the BSO-mediated up-regulation of uncoupling genes results in weight loss that is at least in part ascribed to adipose tissue mass reduction. The induction of thermogenic program has been largely proposed to counteract obesity-related diseases. Based on these findings, we propose GSH as a novel therapeutic target to increase energy expenditure in adipocytes.

Original languageEnglish
Article number13091
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - Aug 11 2015

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this

Lettieri Barbato, D., Tatulli, G., Cannata, S. M., Bernardini, S., Aquilano, K., & Ciriolo, M. R. (2015). Glutathione Decrement Drives Thermogenic Program in Adipose Cells. Scientific Reports, 5, [13091]. https://doi.org/10.1038/srep13091