Effects of leptin on melanin-concentrating hormone expression in the brainof lean and obese Lep(ob)/Lep(ob) mice

The effect of leptin on the expression of melanin-concentrating hormone (MC H) was investigated in lean and genetically obese Lep(ob)/Lep(ob) mice. Mur ine leptin was subcutaneously infused using osmotic minipumps. The treatmen t period extended to 7 days and the daily dose of leptin delivered was 100 mu g/kg of body weight. In situ hybridization was used to assess the effect s of leptin infusion on the expression of MCH mRNA. MCH levels in the brain (hypothalamus/thalamus and the remaining part), spleen and testis were mea sured by radioimmunoassay coupled to HPLC of selected tissue extracts. Lept in significantly reduced final body weight, weight of brown adipose tissue, daily food intake in obese mice but not in lean animals. In obese mice, le ptin led to a rapid reduction in food intake which reached statistical sign ificance after only 24 h and which led to a significant reduction in the bo dy weight after 3 days of treatment. Leptin restored the normal circulating levels of glucose and insulin in obese mice. The present results mainly pr ovide evidence for a stimulating effect of leptin infusion on the MCH neuro nal system. The hypothalamic/thalamic levels of MCH mRNA and peptide were h igher in mice treated with leptin than in mice infused with phosphate-buffe red saline. The stimulation of MCH neurons appeared particularly intense in obese mice, in which the effects of leptin infusion led to the reduction i n MCH content of neuron fibers and terminals. Leptin did not affect spleen and testis MCH contents. In the light of the acknowledged orexigenic effect s of MCH, the results of this study questioned the direct role of MCH in th e action of leptin on energy balance. The increase in MCH expression follow ing leptin could occur as a mechanism to compensate the decrease in energy deposition led to by leptin. It may also indicate that MCH mediates the met abolic actions of leptin indirectly or else that leptin influences actions of MCH other than those related to the regulation of energy balance.