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Dominant Role of the p110β Isoform of PI3K over p110α in Energy Homeostasis Regulation by POMC and AgRP Neurons

Al-Qassab, Hind; Smith, Mark A; Irvine, Elaine E; Guillermet-Guibert, Julie; Claret, Marc; Choudhury, Agharul I; Selman, Colin; ... Withers, Dominic J; + view all (2009) Dominant Role of the p110β Isoform of PI3K over p110α in Energy Homeostasis Regulation by POMC and AgRP Neurons. Cell Metabolism , 10 (5) pp. 343-354. 10.1016/j.cmet.2009.09.008. Green open access

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Abstract

PI3K signaling is thought to mediate leptin and insulin action in hypothalamic pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, through largely unknown mechanisms. We inactivated either p110α or p110β PI3K catalytic subunits in these neurons and demonstrate a dominant role for the latter in energy homeostasis regulation. In POMC neurons, p110β inactivation prevented insulin- and leptin-stimulated electrophysiological responses. POMCp110β null mice exhibited central leptin resistance, increased adiposity, and diet-induced obesity. In contrast, the response to leptin was not blocked in p110α-deficient POMC neurons. Accordingly, POMCp110α null mice displayed minimal energy homeostasis abnormalities. Similarly, in AgRP neurons, p110β had a more important role than p110α. AgRPp110α null mice displayed normal energy homeostasis regulation, whereas AgRPp110β null mice were lean, with increased leptin sensitivity and resistance to diet-induced obesity. These results demonstrate distinct metabolic roles for the p110α and p110β isoforms of PI3K in hypothalamic energy regulation.

Type: Article
Title: Dominant Role of the p110β Isoform of PI3K over p110α in Energy Homeostasis Regulation by POMC and AgRP Neurons
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cmet.2009.09.008
Publisher version: https://doi.org/10.1016/j.cmet.2009.09.008
Language: English
Additional information: Copyright © The Author 2009. This article is licensed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/3.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10159949
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