title: Metabolic responses to leptin in obese db/db mice are strain dependent.
abstract: 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.
authors.affiliation: Departments of Neuroscience and Biostatistics, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA. harrisrb@arches.uga.edu
authors.forename: R B
authors.initials: RB
authors.lastname: Harris
authors.forename: T D
authors.initials: TD
authors.lastname: Mitchell
authors.forename: X
authors.initials: X
authors.lastname: Yan
authors.forename: J S
authors.initials: JS
authors.lastname: Simpson
authors.forename: S M
authors.initials: SM
authors.lastname: Redmann
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C515447:leptin receptor, mouse