A leptin dose-response study in obese (ob/ob) and lean (+/?) mice.
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.
Harris
R B
RB
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA. Harrisb@mhs.pbrc.edu
Zhou
J
J
Redmann
S M
SM
Smagin
G N
GN
Smith
S R
SR
Rodgers
E
E
Zachwieja
J J
JJ
D000818:Animals; D015306:Biogenic Monoamines / Q000032:analysis; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D007328:Insulin / Q000097:blood; D020738:Leptin; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D010053:Ovary / Q000187:drug effects; D011506:Proteins / Q000494:pharmacology*
D015306:Biogenic Monoamines; D007328:Insulin; D020738:Leptin; D011506:Proteins