La proteine Agouti et son role dans les syndromes d'obesite

Translated title of the contribution: The role of the Agouti protein in the yellow mouse obesity syndrome

Research output: Contribution to journalReview article

1 Scopus citations

Abstract

Several dominant mutations at the agouti locus in the mouse cause a syndrome of marked obesity, hyperinsulinemia, insulin resistance, hyperglycemia, increased lean body mass as well as yellow coat color. Dominant obese yellow mutants, such as viable yellow (A(vy)) and lethal yellow (A(y)) exhibit mutations in the promoter region of the agouti gene, resulting in ectopic overexpression of agouti transcripts which contain the entire protein-coding portion in numerous tissues. Transgenic mice in which the wild-type agouti cDNA is placed under the transcriptional control of ubiquitous promoters develop the yellow mouse obesity syndrome, demonstrating that ectopic expression of agouti per se is responsible for this syndrome. While expression of agouti in adipose tissue does not lead to obesity, the combination of hyperinsulinemia and agouti expression in adipose tissue leads to weight gain. The mechanism of agouti regulation of mouse coat color is based upon competitive antagonism of α-melanocyte stimulating hormone (α-MSH) binding at the melanocortin receptor 1 (MC1-R), resulting in suppression of cAMP production and a shift from eumelanin (black pigment) to phaeomelanin (yellow pigment) production. Similar to its action on the skin, agouti acts centrally as an antagonist to α-MSH at the melanocortin receptor (MC-4R). Agouti recombinant protein increases intracellular Ca2+ ([Ca2+]i) signaling in several cell types including adipocytes and stimulates fatty acid and triglyceride synthesis in adipocytes at least in part via a Ca2+-dependent mechanism. Agouti and insulin act in an additive manner to increase fatty acid synthesis in adipocytes. Interestingly, agouti is expressed in human adipose tissue and pancreatic islets where it increases intracellular calcium and insulin secretion.

Translated title of the contributionThe role of the Agouti protein in the yellow mouse obesity syndrome
Original languageFrench
Pages (from-to)898-906
Number of pages9
JournalMedecine/Sciences
Volume14
Issue number8-9
DOIs
StatePublished - 1998

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