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Cellular Energy Depletion Resets Whole-Body Energy by Promoting Coactivator-Mediated Dietary Fuel Absorption.

Authors :
Chopra, Atul R.
Kommagani, Ramakrishna
Saha, Pradip
Louet, Jean-Francois
Salazar, Christina
Song, Junghun
Jeong, Jaewook
Finegold, Milton
Viollet, Benoit
DeMayo, Franco
Chan, Lawrence
Moore, David D.
O'Malley, Bert W.
Source :
Cell Metabolism; Jan2011, Vol. 13 Issue 1, p35-43, 9p
Publication Year :
2011

Abstract

Summary: All organisms have devised strategies to counteract energy depletion and promote fitness for survival. We show here that cellular energy depletion puts into play a surprising strategy that leads to absorption of exogenous fuel for energy repletion. The energy-depletion-sensing kinase AMPK binds, phosphorylates, and activates the transcriptional coactivator SRC-2, which in a liver-specific manner promotes absorption of dietary fat from the gut. Hepatocyte-specific deletion of SRC-2 results in intestinal fat malabsorption and attenuated entry of fat into the blood stream. This defect can be attributed to AMPK- and SRC-2-mediated transcriptional regulation of hepatic bile acid (BA) secretion into the gut, as it can be completely rescued by replenishing intestinal BA or by genetically restoring the levels of hepatic bile salt export pump (BSEP). Our results position the hepatic AMPK-SRC-2 axis as an energy rheostat, which upon cellular energy depletion resets whole-body energy by promoting absorption of dietary fuel. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15504131
Volume :
13
Issue :
1
Database :
Supplemental Index
Journal :
Cell Metabolism
Publication Type :
Academic Journal
Accession number :
57165431
Full Text :
https://doi.org/10.1016/j.cmet.2010.12.001