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

Alex Reichenbach, Romana Stark, Mathieu Mequinion, Sarah H. Lockie, Moyra B. Lemus, Randall L. Mynatt, Serge Luquet, Zane B. Andrews

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)6923-6933
Number of pages11
JournalFASEB Journal
Volume32
Issue number12
DOIs
Publication statusPublished - 1 Dec 2018

Keywords

  • Body composition
  • Feeding behavior
  • Metabolic flexibility
  • Rebound weight gain
  • RER

Cite this

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title = "Carnitine acetyltransferase (Crat) in hunger-sensing AgRP neurons permits adaptation to calorie restriction",
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.",
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Carnitine acetyltransferase (Crat) in hunger-sensing AgRP neurons permits adaptation to calorie restriction. / Reichenbach, Alex; Stark, Romana; Mequinion, Mathieu; Lockie, Sarah H.; Lemus, Moyra B.; Mynatt, Randall L.; Luquet, Serge; Andrews, Zane B.

In: FASEB Journal, Vol. 32, No. 12, 01.12.2018, p. 6923-6933.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Stark, Romana

AU - Mequinion, Mathieu

AU - Lockie, Sarah H.

AU - Lemus, Moyra B.

AU - Mynatt, Randall L.

AU - Luquet, Serge

AU - Andrews, Zane B.

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