PRb is an Obesity Suppressor in Hypothalamus and High-fat Diet Inhibits PRb in This Location

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2013 Feb 14

PMID 23403926

Citations 11

Authors

Zhonglei Lu

Genevieve Marcelin

Frederick Bauzon

Hongbo Wang

Hao Fu

Siok Le Dun

Hongling Zhao

Xiaosong Li

Young-Hwan Jo

Sharon Wardlaw

Nae Dun

Streamson Chua Jr

Liang Zhu

Affiliations

Soon will be listed here.

Abstract

pRb is frequently inactivated in tumours by mutations or phosphorylation. Here, we investigated whether pRb plays a role in obesity. The Arcuate nucleus (ARC) in hypothalamus contains antagonizing POMC and AGRP/NPY neurons for negative and positive energy balance, respectively. Various aspects of ARC neurons are affected in high-fat diet (HFD)-induced obesity mouse model. Using this model, we show that HFD, as well as pharmacological activation of AMPK, induces pRb phosphorylation and E2F target gene de-repression in ARC neurons. Some affected neurons express POMC; and deleting Rb1 in POMC neurons induces E2F target gene de-repression, cell-cycle re-entry, apoptosis, and a hyperphagia-obesity-diabetes syndrome. These defects can be corrected by combined deletion of E2f1. In contrast, deleting Rb1 in the antagonizing AGRP/NPY neurons shows no effects. Thus, pRb-E2F1 is an obesity suppression mechanism in ARC POMC neurons and HFD-AMPK inhibits this mechanism by phosphorylating pRb in this location.

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