AgRP Neurons Require Carnitine Acetyltransferase to Regulate Metabolic Flexibility and Peripheral Nutrient Partitioning.

Autor:	Reichenbach A; Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia; Department of Physiology, Monash University, Clayton 3800, VIC, Australia., Stark R; Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia; Department of Physiology, Monash University, Clayton 3800, VIC, Australia., Mequinion M; Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia; Department of Physiology, Monash University, Clayton 3800, VIC, Australia., Denis RRG; Université of Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionelle et Adaptative, CNRS UMR 8251, 75205 Paris, France., Goularte JF; Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia., Clarke RE; Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia; Department of Physiology, Monash University, Clayton 3800, VIC, Australia., Lockie SH; Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia; Department of Physiology, Monash University, Clayton 3800, VIC, Australia., Lemus MB; Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia; Department of Physiology, Monash University, Clayton 3800, VIC, Australia., Kowalski GM; Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood 3125, VIC, Australia., Bruce CR; Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood 3125, VIC, Australia., Huang C; Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia; Monash Biomedical Proteomics Facility and Department of Biochemistry, Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia., Schittenhelm RB; Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia; Monash Biomedical Proteomics Facility and Department of Biochemistry, Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia., Mynatt RL; Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA; Transgenic Core Facility, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA., Oldfield BJ; Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia; Department of Physiology, Monash University, Clayton 3800, VIC, Australia., Watt MJ; Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia; Department of Physiology, Monash University, Clayton 3800, VIC, Australia., Luquet S; Université of Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionelle et Adaptative, CNRS UMR 8251, 75205 Paris, France., Andrews ZB; Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia; Department of Physiology, Monash University, Clayton 3800, VIC, Australia. Electronic address: zane.andrews@monash.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Feb 13; Vol. 22 (7), pp. 1745-1759.
DOI:	10.1016/j.celrep.2018.01.067
Abstrakt:	AgRP neurons control peripheral substrate utilization and nutrient partitioning during conditions of energy deficit and nutrient replenishment, although the molecular mechanism is unknown. We examined whether carnitine acetyltransferase (Crat) in AgRP neurons affects peripheral nutrient partitioning. Crat deletion in AgRP neurons reduced food intake and feeding behavior and increased glycerol supply to the liver during fasting, as a gluconeogenic substrate, which was mediated by changes to sympathetic output and peripheral fatty acid metabolism in the liver. Crat deletion in AgRP neurons increased peripheral fatty acid substrate utilization and attenuated the switch to glucose utilization after refeeding, indicating altered nutrient partitioning. Proteomic analysis in AgRP neurons shows that Crat regulates protein acetylation and metabolic processing. Collectively, our studies highlight that AgRP neurons require Crat to provide the metabolic flexibility to optimize nutrient partitioning and regulate peripheral substrate utilization, particularly during fasting and refeeding. (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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