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Endocrinology Vol. 139, No. 1 8-19
Copyright © 1998 by The Endocrine Society

ARTICLES

A Leptin Dose-Response Study in Obese (ob/ob) and Lean (+/?) Mice

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

Pennington Biomedical Research Center and the Department of Veterinary Physiology (J.Z.), Pharmacology and Toxicology, Louisiana State University, Baton Rouge, Louisiana 70808

Address all correspondence and requests for reprints to: Ruth Harris, Ph.D., Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, Louisiana 70808. E-mail: Harrisrb{at}mhs.pbrc.edu

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.




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