Document Detail

Role of lipids in the control of food intake.
MedLine Citation:
PMID:  21252653     Owner:  NLM     Status:  Publisher    
PURPOSE OF REVIEW: The classical hypothesis that a decrease in glucose utilization, registered by specific sensors in the brain, leads to hunger was challenged as lipids and amino acids also provide energy for cell metabolism. This review presents recent progress in the knowledge on lipid signals associated with feeding initiation or inhibition. RECENT FINDINGS: Although the brain does not utilize fatty acids as primary energy sources, recent evidence indicates that intermediates of fatty acids metabolism in the hypothalamus serve as sensors of energy status. Pharmacological or genetic inhibition of brain fatty-acid synthase and carnitine palmitoyltransferase-1c results in profound decreases in feeding and body weight in rodents. These effects depend on changes in the intracytoplasmic pool of long-chain fatty-acyl-CoA and malonyl-CoA, an intermediate of the de-novo fatty acid synthesis in neurons that integrate hormonal and nutrient-derived signals to control feeding behaviour. The central regulatory enzyme is AMP-activated protein kinase, which reversibly phosphorylates acetyl-CoA carboxylase and malonyl-CoA decarboxylase, two enzymes that increase the level of malonyl-CoA in the cells when phosphorylated in response to a low intracellular ratio of AMP/ATP due to decrease in glucose oxidation. SUMMARY: Such a mechanism is compatible with a central energostatic control of feeding based on glucose utilization by neurons and opens new therapeutic perspectives to develop pharmacological compounds that act at the level of pivotal enzymes such as AMP-activated protein kinase, acetyl-CoA carboxylase, malonyl-CoA decarboxylase, and module malonyl-CoA level in cells, to favour central inhibition of feeding.
Marc Fantino
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-19
Journal Detail:
Title:  Current opinion in clinical nutrition and metabolic care     Volume:  -     ISSN:  1535-3885     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9804399     Medline TA:  Curr Opin Clin Nutr Metab Care     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Medical School Hospital of the Burgundy University, Dijon, France.
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