Journal article
AgRP Neurons Require Carnitine Acetyltransferase to Regulate Metabolic Flexibility and Peripheral Nutrient Partitioning
A Reichenbach, R Stark, M Mequinion, RRG Denis, JF Goularte, RE Clarke, SH Lockie, MB Lemus, GM Kowalski, CR Bruce, C Huang, RB Schittenhelm, RL Mynatt, BJ Oldfield, MJ Watt, S Luquet, ZB Andrews
Cell Reports | CELL PRESS | Published : 2018
Abstract
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 af..
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Grants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank Minh Deo technical assistance. We acknowledge Monash FlowCore for sorting of cells using FACS. We acknowledge use of the facilities at the Monash Biomedical Proteomics Facility and the Monash Histology Platform. We thank Doug Compton from Research Diets for helping to set up and establish BioDAQ feeding cages. This study was supported by an Australian NHMRC grant and fellowship (1126724 and 1084344 to Z.B.A. and APP1077703 to M.J.W.). This work used the PBRC Transgenic Core, which is supported in part by COBRE (NIH 8P20GM103528) and NORC (NIH 2P30-DK072476-11A1) center grants from the NIH. A.R. is supported by an Australian Government Research Training Program scholarship. J.F.G. is the recipient of funding from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq Brazil.