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-MSH on food
intake, adiposity, c-Fos induction, and neuropeptide
expression
1 Program in Nutritional Sciences, Departments of 2 Psychiatry and Behavioral Sciences and 6 Medicine, University of Washington, Seattle 98195, 3 Puget Sound Veterans Affairs Health Care System, Seattle 98108, 7 Harborview Medical Center, Seattle, Washington 98104; 4 Department of Nutrition, University of California at Davis, Davis, California 95616; and 5 Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio 45267
-Melanocyte-stimulating hormone (-MSH) is a hypothalamic
neuropeptide proposed to play a key role in energy homeostasis. To
investigate the behavioral, metabolic, and hypothalamic responses to
chronic central -MSH administration, -MSH was infused
continuously into the third cerebral ventricle of rats for 6 days.
Chronic -MSH infusion reduced cumulative food intake by 10.7%
(P < 0.05 vs. saline) and body weight by 4.3%
(P < 0.01 vs. saline), which in turn lowered plasma
insulin levels by 29.3% (P < 0.05 vs. saline). However, -MSH did not cause adipose-specific wasting nor did it
alter hypothalamic neuropeptide mRNA levels. Central -MSH infusion
acutely activated neurons in forebrain areas such as the hypothalamic
paraventricular nucleus, as measured by a 254% increase in c-Fos-like
immunoreactivity (P < 0.01 vs. saline), as well as
satiety pathways in the hindbrain. Our findings suggest that, although
an increase of central melanocortin receptor signaling acutely reduces
food intake and body weight, its anorectic potency wanes during chronic
infusion and causes only a modest decrease of body weight.
melanocortin; hypothalamus; body weight
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