PRb is an obesity suppressor in hypothalamus and high‐fat diet inhibits pRb in this location. (12th February 2013)

• Record Type: Journal Article
• Authors: Lu, Zhonglei; Marcelin, Genevieve; Bauzon, Frederick; Wang, Hongbo; Fu, Hao; Dun, Siok Le; Zhao, Hongling; Li, Xiaosong; Jo, Young‐Hwan; Wardlaw, Sharon; Dun, Nae; Chua, Streamson; Zhu, Liang
• Is Part Of: EMBO journal. Volume 32:Number 6(2013)
• Page Start: 844
• Page End: 857
• Publication Date: 2013-02-12
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.1038/emboj.2013.25
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>Rb1</italic> 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 <italic>E2f1</italic>. In contrast, deleting <italic>Rb1</italic> 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.</p> </abstract>