Open AccessAgouti/Melanocortin Interactions with Leptin Pathways in Obesity
Author(s) -
Zemel Michael B.,
Xue Bingzhong
Publication year - 1998
Publication title -
nutrition reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.958
H-Index - 150
eISSN - 1753-4887
pISSN - 0029-6643
DOI - 10.1111/j.1753-4887.1998.tb01764.x
Subject(s) - leptin , medicine , endocrinology , melanocortin 4 receptor , melanocortin , adipocyte , melanocortin receptor , biology , leptin receptor , melanocortin 3 receptor , hyperinsulinemia , receptor , obesity , adipose tissue , hormone , insulin resistance
The cloning of mouse obesity genes and their human homologues provides unique opportunities to identify novel cellular targets for therapeutic intervention. The first of these to be cloned, agouti, antagonizes central nervous system melanocortin receptor (MCR) binding, resulting in hyperphagia and an obesity/hyperinsulinemia syndrome. There appears to be significant crosstalk between the agouti and leptin signaling systems. Agouti antagonism of central nervous system (CNS) MCR binding inhibits the anorexic effects of leptin, whereas agouti up‐regulates adipocyte leptin expression, serving to limit the magnitude of agouti‐induced obesity. The effects of agouti and leptin mutations on obesity, however, are independent and additive. Agouti also regulates adipocyte lipid metabolism, functioning both to increase the expression and activity of lipogenic genes and to inhibit lipolysis. Both of these actions occur via a Ca 2+ ‐dependent mechanism, suggesting that modulation of adipocyte Ca 2+ transport may be a key target for further investigation.