The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis

Michael J Wolfgang, Takeshi Kurama, Yun Dai, Akira Suwa, Makoto Asaumi, Shun Ichiro Matsumoto, Seung Hun Cha, Teruhiko Shimokawa, M. Daniel Lane

Research output: Contribution to journalArticle

Abstract

Fatty acid synthesis in the central nervous system is implicated in the control of food intake and energy expenditure. An intermediate in this pathway, malonyl-CoA, mediates these effects. Malonyl-CoA is an established inhibitor of carnitine palmitoyltransferase-1 (CPT1), an outer mitochondrial membrane enzyme that controls entry of fatty acids into mitochondria and, thereby, fatty acid oxidation. CPT1c, a brain-specific enzyme with high sequence similarity to CPT1a (liver) and CPT1b (muscle) was recently discovered. All three CPTs bind malonyl-CoA, and CPT1a and CPT1b catalyze acyl transfer from various fatty acyl-CoAs to carnitine, whereas CPT1c does not. These findings suggest that CPT1c has a unique function or activation mechanism. We produced a targeted mouse knockout (KO) of CPT1c to investigate its role in energy homeostasis. CPT1c KO mice have lower body weight and food intake, which is consistent with a role as an energy-sensing malonyl-CoA target. Paradoxically, CPT1c KO mice fed a high-fat diet are more susceptible to obesity, suggesting that CPT1c is protective against the effects of fat feeding. CPT1c KO mice also exhibit decreased rates of fatty acid oxidation, which may contribute to their increased susceptibility to diet-induced obesity. These findings indicate that CPTIc is necessary for the regulation of energy homeostasis.

Original languageEnglish (US)
Pages (from-to)7282-7287
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number19
DOIs
StatePublished - May 9 2006

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Malonyl Coenzyme A
Carnitine O-Palmitoyltransferase
Knockout Mice
Homeostasis
Fatty Acids
Brain
Obesity
Eating
Carnitine
Mitochondrial Membranes
High Fat Diet
Enzymes
Energy Metabolism
Mitochondria
Central Nervous System
Fats
Body Weight
Diet
Muscles
Liver

Keywords

  • Acetyl-coA carboxylase
  • Fatty acid synthase
  • Food intake
  • Malonyl-CoA
  • Obesity

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis. / Wolfgang, Michael J; Kurama, Takeshi; Dai, Yun; Suwa, Akira; Asaumi, Makoto; Matsumoto, Shun Ichiro; Cha, Seung Hun; Shimokawa, Teruhiko; Lane, M. Daniel.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 19, 09.05.2006, p. 7282-7287.

Research output: Contribution to journalArticle

Wolfgang, Michael J ; Kurama, Takeshi ; Dai, Yun ; Suwa, Akira ; Asaumi, Makoto ; Matsumoto, Shun Ichiro ; Cha, Seung Hun ; Shimokawa, Teruhiko ; Lane, M. Daniel. / The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 19. pp. 7282-7287.
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