A leptin dose-response study in obese (ob/ob) and lean (+/?) mice

Ruth B.S. Harris, Jun Zhou, Stephen M. Redmann, Gennady N. Smagin, Steven R. Smith, Erin Rodgers, Jeffrey J. Zachwieja

Research output: Contribution to journalArticlepeer-review

263 Scopus citations


This experiment determined the amount of leptin required to correct different abnormalities in leptin-deficient ob/ob mice. Baseline food intakes and body weights of lean (+/?) and obese (ob/ob) C57Bl/6J <ob= mice were recorded for 7 days. An Alzet miniosmotic pump was placed in the peritoneal cavity of each mouse and delivered 0, 1, 2, 5, 10, or 42 μg/day human leptin for 7 days. In ob/ob mice, 2 μg leptin/day reduced food intake and body weight, and increased hypothalamic and brain stem serotonin concentrations. All fat pads were reduced 35-40% by 10 μg leptin/day, and liver weight, lipid, and glycogen decreased. Serum insulin and glucose were reduced in all leptin-treated ob/ob mice, and levels were normalized by 10 μg/day leptin. Low rectal temperatures of ob/ob mice were corrected by 10 and 42 μg/day leptin. These doses also increased brown adipose tissue uncoupling protein expression. The only responses in lean mice were a transient reduction in food intake and weight loss with 10 or 42 μg/day leptin. This study shows enhanced leptin sensitivity in ob/ob mice and suggests that increased temperature and sympathetic activity are indirect responses to high concentrations of protein.

Original languageEnglish (US)
Pages (from-to)8-19
Number of pages12
Issue number1
StatePublished - Jan 1998
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology


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