Liver-Specific Activation of AMPK Prevents Steatosis on a High-Fructose Diet.

Autor:	Woods A; MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital, London W12 0NN, UK. Electronic address: angela.woods@lms.mrc.ac.uk., Williams JR; MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital, London W12 0NN, UK., Muckett PJ; MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital, London W12 0NN, UK., Mayer FV; MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital, London W12 0NN, UK., Liljevald M; Drug Safety and Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal 431 83, Sweden., Bohlooly-Y M; Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal 431 83, Sweden., Carling D; MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital, London W12 0NN, UK; Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital, London W12 0NN, UK. Electronic address: david.carling@lms.mrc.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2017 Mar 28; Vol. 18 (13), pp. 3043-3051.
DOI:	10.1016/j.celrep.2017.03.011
Abstrakt:	AMP-activated protein kinase (AMPK) plays a key role in integrating metabolic pathways in response to energy demand. We identified a mutation in the γ1 subunit (γ1 D316A ) that leads to activation of AMPK. We generated mice with this mutation to study the effect of chronic liver-specific activation of AMPK in vivo. Primary hepatocytes isolated from these mice have reduced gluconeogenesis and fatty acid synthesis, but there is no effect on fatty acid oxidation compared to cells from wild-type mice. Liver-specific activation of AMPK decreases lipogenesis in vivo and completely protects against hepatic steatosis when mice are fed a high-fructose diet. Our findings demonstrate that liver-specific activation of AMPK is sufficient to protect against hepatic triglyceride accumulation, a hallmark of non-alcoholic fatty liver disease (NAFLD). These results emphasize the clinical relevance of activating AMPK in the liver to combat NAFLD and potentially other associated complications (e.g., cirrhosis and hepatocellular carcinoma). (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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