Hsp90 blockers inhibit adipocyte differentiation and fat mass accumulation

Sébastien Desarzens, Wan Hui Liao, Caterina Mammi, Massimiliano Caprio, Nourdine Faresse

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Geldanamycin derivatives are benzoquinone ansamycin antibiotics that bind to Hsp90 and alter its function. The alteration of Hsp90 activity limits some cellular hormonal responses by inhibiting nuclear receptors activation. The nuclear receptors activity, such as PPARc, the mineralocorticoid and glucocorticoid receptors (MR and GR) play a critical role in the conversion of preadipocytes to mature adipocytes. Given the importance of these nuclear receptors for adipogenesis, we investigated the effects of geldanamycin analogues (GA) on adipocyte differentiation and function. We found that early exposure of preadipocyte cells to GA inhibited their conversion into mature adipocytes by inhibiting the adipogenic transcriptional program and lipid droplets accumulation. Furthermore, GA altered the adipokines secretion profile of mature adipocyte. The anti-adipogenic effect of GA was also confirmed in mice fed a high fat diet. Biochemical analysis revealed that anti-adipogenic effects of geldanamycin analogues may result from the simultaneous inhibition of MR, GR and PPARγ activity. Taken together, our observations lead us to propose Hsp90 as a potent target for drug development in the control of obesity and its related metabolic complications.

Original languageEnglish
Article numbere94127
JournalPLoS One
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 4 2014

Fingerprint

adipocytes
Adipocytes
Fats
Cytoplasmic and Nuclear Receptors
lipids
receptors
adipokines
benzoquinones
high fat diet
Rifabutin
droplets
Mineralocorticoid Receptors
Adipogenesis
Peroxisome Proliferator-Activated Receptors
Adipokines
obesity
antibiotics
Glucocorticoid Receptors
High Fat Diet
secretion

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hsp90 blockers inhibit adipocyte differentiation and fat mass accumulation. / Desarzens, Sébastien; Liao, Wan Hui; Mammi, Caterina; Caprio, Massimiliano; Faresse, Nourdine.

In: PLoS One, Vol. 9, No. 4, e94127, 04.04.2014.

Research output: Contribution to journalArticle

Desarzens, Sébastien ; Liao, Wan Hui ; Mammi, Caterina ; Caprio, Massimiliano ; Faresse, Nourdine. / Hsp90 blockers inhibit adipocyte differentiation and fat mass accumulation. In: PLoS One. 2014 ; Vol. 9, No. 4.
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