Metabolic responses to leptin in obese db/db mice are strain dependent.
Obese, diabetic C57BL/Ks db/db mice that lack the long-form leptin receptor exhibit no decrease in body weight or food intake when treated with leptin. Here we compared responses to leptin in two strains of db/db mice: C57BL/6J mice that are hyperglycemic and hyperinsulinemic and C57BL/Ks that are hyperglycemic and normo- or hypoinsulinemic. Chronic intraperitoneal infusion of 10 microgram leptin/day partially reversed hyperglycemia in C57BL/6J male mice but exaggerated the diabetic state of female mice. Bolus intraperitoneal injections of 40 microgram leptin/day did not effect glucose in either strain of male db/db mice, whereas chronic intraperitoneal infusion of 20 microgram leptin/day significantly reduced fasting blood glucose in male mice from both strains, especially C57BL/6J mice. Food intake, body weight, rectal temperature, and body fat did not change. Chronic intraperitoneal infusion of 10 microgram leptin/day significantly reduced body fat in lean db/+ C57BL/6J but not in C57BL/Ks mice. Thus peripherally administered leptin is active in mice that have only short-form leptin receptors, and the response is dependent on the method of leptin administration and the background strain.
Harris
R B
RB
Departments of Neuroscience and Biostatistics, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA. harrisrb@arches.uga.edu
Mitchell
T D
TD
Yan
X
X
Simpson
J S
JS
Redmann
S M
SM
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D005215:Fasting / Q000502:physiology; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006720:Homozygote; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism; D007263:Infusions, Parenteral; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese / Q000378:metabolism*; D009765:Obesity; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D013045:Species Specificity
D001786:Blood Glucose; D002352:Carrier Proteins; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C515447:leptin receptor, mouse