Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting in ob/ob and db/db mice, but is stimulated by leptin

Tooru M. Mizuno, Steven P. Kleopoulos, Hugo T. Bergen, James L. Roberts, Catherine A. Priest, Charles V. Mobbs

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Abstract

Reduction in the activity of the a-melanocyte-stimulating hormone (α- MSH) system causes obesity, and infusions of α-MSH can produce satiety, raising the possibility that α-MSH may mediate physiological satiety signals. Since α-MSH is coded for by the pro-opiomelanocortin (POMC) gene, we examined if POMC gene expression would be inhibited by fasting in normal mice or in models of obesity characterized by leptin insufficiency (ob/ob) or leptin insensitivity (db/db). In wild-type mice, hypothalamic POMC mRNA was decreased >60% after a 2-day fast and was positively correlated with leptin mRNA. Similarly, compared with controls, POMC mRNA was decreased by at least 60% in both db/db and ob/ob mice. POMC mRNA was negatively correlated with both neuropeptide Y (NPY) and melanin-concentrating hormone (MCH) mRNA. Finally, treatment of both male and female ob/ob mice with leptin stimulated hypothalamic POMC mRNA by about threefold. These results suggest that impairment in production, processing, or responsiveness to α-MSH may be a common feature of obesity and that hypothalamic POMC neurons, stimulated by leptin, may constitute a link between leptin and the melanocortin system.

Original languageEnglish (US)
Pages (from-to)294-297
Number of pages4
JournalDiabetes
Volume47
Issue number2
DOIs
StatePublished - Jan 1 1998

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Mizuno, T. M., Kleopoulos, S. P., Bergen, H. T., Roberts, J. L., Priest, C. A., & Mobbs, C. V. (1998). Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting in ob/ob and db/db mice, but is stimulated by leptin. Diabetes, 47(2), 294-297. https://doi.org/10.2337/diab.47.2.294