In-vivo hypocalcaemic, hypophosphataemic and hyperlipaemic activities in the common peptide sequence of adrenocorticotrophin, melanocyte-stimulating hormone and lipotrophin

Drouhault, R; Valéro, Danièle; Baghdiantz, A; Blanquet, P

doi:10.1677/joe.0.0970447

Cited by 3 publications

(1 citation statement)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The lipolytic activity we observed of MSH in mice in vivo is similar to the high lipolytic activity of MSH seen in rabbits in vivo (41). In the rabbit experiments i.v.…”

Section: Discussionsupporting

confidence: 86%

Integrated control of appetite and fat metabolism by the leptin-proopiomelanocortin pathway

Forbes

Bui

Robinson

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

126

View full text Add to dashboard Cite

Leptin deficiency results in a complex obesity phenotype comprising both hyperphagia and lowered metabolism. The hyperphagia results, at least in part, from the absence of induction by leptin of melanocyte stimulating hormone (MSH) secretion in the hypothalamus; the MSH normally then binds to melanocortin-4 receptor expressing neurons and inhibits food intake. The basis for the reduced metabolic rate has been unknown. Here we show that leptin administered to leptin-deficient (ob͞ob) mice results in a large increase in peripheral MSH levels; further, peripheral administration of an MSH analogue results in a reversal of their abnormally low metabolic rate, in an acceleration of weight loss during a fast, in partial restoration of thermoregulation in a cold challenge, and in inducing serum free fatty acid levels. These results support an important peripheral role for MSH in the integration of metabolism with appetite in response to perceived fat stores indicated by leptin levels.R ecent research has outlined a pathway for control of body weight (1-4): leptin, the product of the ob gene in mouse, is produced by adipocytes (5). It circulates to the hypothalamus where it binds to cells expressing the leptin receptor, the product of the db gene in mouse (6-9). Proopiomelanocortin (POMC) neurons are among the hypothalamic neurons expressing the leptin receptor (10). This leptin binding leads to the secretion of melanocyte stimulating hormone (MSH), which in turn binds to neurons expressing the melanocortin-4 receptor (MC4-R) (11); these neurons then suppress appetite (12)(13)(14). This outline is based on the phenotypes of spontaneous and induced mouse mutants (5,9,13,(15)(16)(17)(18)(19) as well as on the phenotype of homologous mutations in humans (20-24). These interpretations are in agreement that leptin is the signal from the fat stores (adipocytes) to the center, and further that MSH regulates appetite. However, there are significant aspects of the mutant phenotypes that suggest both a greater complexity of body weight homeostasis, specifically the integration of appetite and metabolism, and a factor from the central nervous system (CNS) to the periphery mediating this integration.First, pomc͞pomc mutants that completely lack POMC peptides, including MSH, show a phenotype of altered lipid metabolism in addition to hyperphagia. As the fat content of the diet increases, the mice gain weight out of proportion to their food intake (17). This shows a particular inability to use dietary fat for sustaining metabolic rate. And when these pomc͞pomc mutants are treated by peripheral administration of an ␣-MSH analog the mice lose weight and eat less, but the weight loss is much greater than the decrease in appetite (17). Again, this result is consistent with a role for MSH in mobilizing peripheral fat stores.Second, leptin-deficient mice (ob͞ob) show decreased metabolic rate (increased metabolic efficiency; ref. 25), which precedes the onset of obesity. Notably these mutants show: (i) weight gain when pair-fed with normal c...

show abstract

“…The lipolytic activity we observed of MSH in mice in vivo is similar to the high lipolytic activity of MSH seen in rabbits in vivo (41). In the rabbit experiments i.v.…”

Section: Discussionsupporting

confidence: 86%