Localization and effect of ectopic expression of CPT1c in CNS feeding centers

Yun Dai, Michael J. Wolfgang, Seung Hun Cha, M. Daniel Lane

Research output: Contribution to journalArticlepeer-review

Abstract

Hypothalamic neurons monitor peripheral energy status and produce signals to adjust food intake and energy expenditure to maintain homeostasis. However, the molecular mechanisms by which these signals are generated remain unclear. Fluctuations in the level of hypothalamic malonyl-CoA are known to serve as an intermediary in regulating energy homeostasis and it has been proposed that the brain-specific carnitine palmitoyltransferase-1c (CPT1c) serves as a target of malonyl-CoA in the central nervous system (CNS). Here, we report that CPT1c is widely expressed in neurons throughout the CNS including the hypothalamus, hippocampus, cortex, and amygdala. CPT1c is enriched in neural feeding centers of the hypothalamus with mitochondrial localization as an outer integral membrane protein. Ectopic over-expression of CPT1c by stereotactic hypothalamic injection of a CPT1c adenoviral vector is sufficient to protect mice from body weight gain when fed a high-fat diet. These findings show that CPT1c is appropriately localized in regions and cell types to regulate energy homeostasis and that its over-expression in the hypothalamus is sufficient to protect mice from adverse weight gain caused by high-fat intake.

Original languageEnglish (US)
Pages (from-to)469-474
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume359
Issue number3
DOIs
StatePublished - Aug 3 2007

Keywords

  • AMPK
  • Acetyl-CoA carboxylase
  • Carnitine palmitoyltransferase-1c
  • Fatty acid synthase
  • Malonyl-CoA
  • Obesity

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Localization and effect of ectopic expression of CPT1c in CNS feeding centers'. Together they form a unique fingerprint.

Cite this