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Genetic Background (C57BL/6J Versus FVB/N) Strongly Influences the Severity of Diabetes and Insulin Resistance in ob/ob Mice

Diabetes Branch (M.H., C.C., O.G., B.S., K.R.D., D.L.R., M.L.R.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Third Department of Medicine (M.H.), First Faculty of Medicine, Charles University, 12808 Prague-2, Czech Republic; Division of Molecular Genetics and New York Obesity Research Center (S.C.), Department of Pediatrics, Columbia University, New York, New York 10032; and Metabolic Diseases Branch (N.W., M.C.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Martin Haluzik, Third Department of Medicine, First Faculty of Medicine, Charles University, U nemocnice 1, 12808, Prague-2, Czech Republic. E-mail: mhalu{at}lf1.cuni.cz.

We studied the effects of genetic background on the phenotype of ob/ob mice, a model of severe obesity, insulin resistance, and diabetes caused by leptin deficiency. Despite a comparable degree of obesity and hyperinsulinemia, C57BL/6J ob/ob mice had much milder hyperglycemia and, surprisingly, normal circulating adiponectin levels despite still-prominent signs of insulin resistance. Hyperinsulinemic-euglycemic clamp revealed relatively less whole-body and muscle insulin resistance in C57BL/6J ob/ob mice, whereas liver insulin resistance tended to be more severe than in FVB/N ob/ob mice. C57BL/6J ob/ob mice had also more rapid clearance of circulating triglycerides and more severe hepatic steatosis. We suggest that strain-related distinction in lipid handling is the most important player in the differences in diabetic phenotype and insulin sensitivity, whereas the impact of circulating adiponectin levels on the overall phenotype of ob/ob mice is less important.

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