Adipose Tissue-specific Inactivation of the Retinoblastoma Protein Protects Against Diabesity Because of Increased Energy Expenditure

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Jun 9

PMID 17556545

Citations 51

Authors

Nassim Dali-Youcef

Chikage Mataki

Agnes Coste

Nadia Messaddeq

Sylvain Giroud

Stephane Blanc

Christian Koehl

Marie-France Champy

Pierre Chambon

Lluis Fajas

Daniel Metzger

Kristina Schoonjans

Johan Auwerx

Affiliations

Soon will be listed here.

Abstract

The role of the tumor suppressor retinoblastoma protein (pRb) has been firmly established in the control of cell cycle, apoptosis, and differentiation. Recently, it was demonstrated that lack of pRb promotes a switch from white to brown adipocyte differentiation in vitro. We used the Cre-Lox system to specifically inactivate pRb in adult adipose tissue. Under a high-fat diet, pRb-deficient (pRb(ad-/-)) mice failed to gain weight because of increased energy expenditure. This protection against weight gain was caused by the activation of mitochondrial activity in white and brown fat as evidenced by histologic, electron microscopic, and gene expression studies. Moreover, pRb(-/-) mouse embryonic fibroblasts displayed higher proliferation and apoptosis rates than pRb(+/+) mouse embryonic fibroblasts, which could contribute to the altered white adipose tissue morphology. Taken together, our data support a direct role of pRb in adipocyte cell fate determination in vivo and suggest that pRb could serve as a potential therapeutic target to trigger mitochondrial activation in white adipose tissue and brown adipose tissue, favoring an increase in energy expenditure and subsequent weight loss.

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