Characterization of melanin concentrating hormone and preproorexin expression in the murine hypothalamus

Melanin concentrating hormone (MCH) and the orexins (A and B) have been ide ntified as neuropeptides localized to the lateral hypothalamic area (LHA) a nd are potential regulators of energy homeostasis. Potential factors regula ting expression of both MCH and the orexins include fasting and leptin. Pre vious studies have generated conflicting data and, as there is little lepti n receptor expressed in the lateral hypothalamus. it is likely that any obs erved leptin effects on these peptides are indirect. In this study, we exam ined MCH and preproorexin expression in mice in physiological states of sta rvation, with or without leptin administration, in addition to characterizi ng MCH and preproorexin expression in well-known obesity models, including ob/ob and UCP-DTA mice. Neuropeptide Y (NPY) expression in the arcuate nucl eus was used as a positive control. After a 60-h fast, expression of both N PY and MCH mRNA was increased (by 148 and 33%, respectively) while preproor exin expression in the murine LHA did not change. Leptin administration to fasted mice blunted the rise in MCH and NPY expression towards control leve ls. In contrast, there was a 78% increase in preproorexin expression in fas ted mice in response to peripheral leptin administration. MCH expression wa s increased (by 116%) in ob/ob mice at baseline. as we have previously repo rted. In addition, leptin treatment of ob/ob mice blunted the increase in M CH expression. In contrast, preproorexin expression did not differ in the l eptin-deficient ob/ob mice or in the obese hyperleptinemic brown adipose ti ssue deficient (UCP-DTA) mice in comparison with controls. In summary. MCH expression is increased in two states of decreased leptin, fasting and ob/o b mice, and leptin replacement blunts MCH expression in both paradigms. Thu s, MCH expression appears to be regulated by leptin. In contrast, preproore xin expression does not respond acutely to fasting, although it is acutely increased by leptin treatment during fasting. These preproorexin responses are in contrast to those seen with well-characterized orexigenic neuropepti des, such as NPY and AgRP, suggesting that appetite regulation may not be a significant physiological role of orexins. This conclusion is further supp orted by the observation that orexin ablated mice have arousal and not feed ing deficits. (C) 2001 Elsevier Science B.V. All rights reserved.