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Experimental Biology and Medicine 228:24-32 (2003)
© 2003 Society for Experimental Biology and Medicine

ORIGINAL RESEARCH ARTICLE

Leptin-Induced Changes in Body Composition in High Fat-Fed Mice1

Ruth B.S. Harris2, Tiffany D. Mitchell and Sadie Hebert

Pennington Biomedical Research Center, Baton Rouge, LA 70808

Female C57BL/6J mice were adapted to 10% or 45% kcal fat diets for 8 weeks. Continuous intraperitoneal infusion of 10 µg of leptin/day from a miniosmotic pump transiently inhibited food intake in low fat-fed but not high fat-fed mice. In contrast, both low and high fat-fed leptin-infused mice were less fat than their phosphate-buffered saline (PBS) controls after 13 days. Leptin infusion inhibited insulin release but did not change glucose clearance in low fat-fed mice during a glucose tolerance test. A single intraperitoneal injection of 30 µg of leptin inhibited 24-hr energy intake and inhibited weight gain in both low and high fat-fed mice. Insulin responsiveness was improved in high fat-fed mice during an insulin sensitivity test due to an exaggerated elevation of circulating insulin concentrations. Thus, leptin infusion reduced adiposity independently of energy intake in high fat-fed mice and improved insulin sensitivity in low fat-fed mice, whereas leptin injections, which produced much greater, but transient, increases in serum leptin concentration, inhibited energy intake in both low and high fat-fed mice.

Key Words: leptin infusion • leptin injection • leptin resistance • body composition • IRS protein




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