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Publication : Cellular energy depletion resets whole-body energy by promoting coactivator-mediated dietary fuel absorption.

First Author  Chopra AR Year  2011
Journal  Cell Metab Volume  13
Issue  1 Pages  35-43
PubMed ID  21195347 Mgi Jnum  J:169479
Mgi Id  MGI:4941094 Doi  10.1016/j.cmet.2010.12.001
Citation  Chopra AR, et al. (2011) Cellular energy depletion resets whole-body energy by promoting coactivator-mediated dietary fuel absorption. Cell Metab 13(1):35-43
abstractText  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.
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