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FASEB J. 2018 Jun 22:fj201800634R. doi: 10.1096/fj.201800634R. [Epub ahead of print]

Carnitine acetyltransferase (Crat) in hunger-sensing AgRP neurons permits adaptation to calorie restriction.

Author information

1
Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
2
Department of Physiology, Monash University, Clayton, Victoria, Australia.
3
Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
4
Transgenic Core Facility, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA; and.
5
Université of Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionelle et Adaptative, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche 8251, Paris, France.

Abstract

Hunger-sensing agouti-related peptide (AgRP) neurons ensure survival by adapting metabolism and behavior to low caloric environments. This adaption is accomplished by consolidating food intake, suppressing energy expenditure, and maximizing fat storage (nutrient partitioning) for energy preservation. The intracellular mechanisms responsible are unknown. Here we report that AgRP carnitine acetyltransferase (Crat) knockout (KO) mice exhibited increased fatty acid utilization and greater fat loss after 9 d of calorie restriction (CR). No differences were seen in mice with ad libitum food intake. Eleven days ad libitum feeding after CR resulted in greater food intake, rebound weight gain, and adiposity in AgRP Crat KO mice compared with wild-type controls, as KO mice act to restore pre-CR fat mass. Collectively, this study highlights the importance of Crat in AgRP neurons to regulate nutrient partitioning and fat mass during chronically reduced caloric intake. The increased food intake, body weight gain, and adiposity in KO mice after CR also highlights the detrimental and persistent metabolic consequence of impaired substrate utilization associated with CR. This finding may have significant implications for postdieting weight management in patients with metabolic diseases.-Reichenbach, A., Stark, R., Mequinion, M., Lockie, S. H., Lemus, M. B., Mynatt, R. L., Luquet, S., Andrews, Z. B. Carnitine acetyltransferase (Crat) in hunger-sensing AgRP neurons permits adaptation to calorie restriction.

KEYWORDS:

RER; body composition; feeding behavior; metabolic flexibility; rebound weight gain

PMID:
29932868
PMCID:
PMC6219829
[Available on 2019-12-01]
DOI:
10.1096/fj.201800634R

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