1. Cellular energy depletion resets whole-body energy by promoting coactivator-mediated dietary fuel absorption.
- Author
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Chopra AR, Kommagani R, Saha P, Louet JF, Salazar C, Song J, Jeong J, Finegold M, Viollet B, DeMayo F, Chan L, Moore DD, and O'Malley BW
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Member 11, ATP-Binding Cassette Transporters biosynthesis, ATP-Binding Cassette Transporters genetics, Ablation Techniques, Animals, Bile Acids and Salts metabolism, Cells, Cultured, Energy Metabolism, Gene Expression Regulation, Hep G2 Cells, Hepatocytes enzymology, Hepatocytes metabolism, Humans, Intestinal Absorption, Liver cytology, Liver enzymology, Liver metabolism, Malabsorption Syndromes metabolism, Malabsorption Syndromes pathology, Male, Mice, Mice, Knockout, Nuclear Receptor Coactivator 2 genetics, Phosphorylation, Promoter Regions, Genetic, RNA-Binding Proteins metabolism, Transcriptional Activation, AMP-Activated Protein Kinases metabolism, ATP-Binding Cassette Transporters metabolism, Dietary Fats metabolism, Nuclear Receptor Coactivator 2 deficiency, Nuclear Receptor Coactivator 2 metabolism
- Abstract
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., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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