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

Endocrinology. 1998 Jan;139(1):8-19. doi: 10.1210/endo.139.1.5675.


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) C57B1/6J <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 microg/day human leptin for 7 days. In ob/ob mice, 2 microg 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 microg 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 microg/day leptin. Low rectal temperatures of ob/ob mice were corrected by 10 and 42 microg/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 microg/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.

MeSH terms

  • Animals
  • Biogenic Monoamines / analysis
  • Body Temperature / drug effects
  • Body Weight / drug effects
  • Brain Chemistry / drug effects
  • Dose-Response Relationship, Drug
  • Eating / drug effects
  • Female
  • Insulin / blood
  • Leptin
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Ovary / drug effects
  • Proteins / pharmacology*


  • Biogenic Monoamines
  • Insulin
  • Leptin
  • Proteins