Genetic evidence for discordance between obesity- and diabetes-related traits in the LGXSM recombinant inbred mouse strains

James M. Cheverud, Thomas H. Ehrich, Jane P. Kenney, L. Susan Pletscher, Clay F. Semenkovich

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Obesity and its comorbidities, particularly type 2 diabetes, have become serious public health problems over the past few decades. Although the current pandemic is largely caused by societal environmental changes in diet, variation in response to these changes have, in part, a genetic basis. Here we address the genetic basis for both obesity- and diabetes-related traits themselves and dietary fat responses for these traits in a set of recombinant inbred mouse strains formed from the cross of LG/J with SM/J (LGXSM lines) fed a standard low-fat (15% calories from fat) or high-fat (42% calories from fat) diet. We found substantial genetic variation for most of the traits studied. Weight at time of death, liver weight, and weight of the reproductive fat pad had especially high heritabilities, whereas heart weight and serum levels of free fatty acids and triglycerides had low heritabilities. Genetic correlations were very high among fat pad weights and serum leptin, indicating shared genetic variation between fat levels and hormonal appetite control. These obesity traits were moderately correlated with adult growth, liver weight, and serum insulin and cholesterol levels. A majority of traits also displayed genetic variation in response to a high-fat diet, especially the weight of the reproductive and renal fat pads as well as the liver. Genetic correlations in dietary response followed a pattern similar to that found for the traits themselves. Several strains manifested discordant responses for obesity, glucose, and insulin, consistent with the presence of genotypes protective for diabetes in the presence of obesity. These recombinant inbred strains represent potentially valuable new models for dissecting the complex physiological relationships among obesity and diabetes.

Original languageEnglish
Pages (from-to)2700-2708
Number of pages9
Issue number10
StatePublished - Oct 2004


Dive into the research topics of 'Genetic evidence for discordance between obesity- and diabetes-related traits in the LGXSM recombinant inbred mouse strains'. Together they form a unique fingerprint.

Cite this