Genetic analysis of abdominal fat distribution in SM/J and A/J mice

Abstract

Each abdominal fat depot, such as mesenteric or epididymal, differently contributes to the development of insulin resistance. The aim of this study was to identify the genetic regions that contribute to fat accumulation in epididymal/mesenteric fat and to examine whether or not the genetic regions that affect glucose metabolism and body fat distribution are coincident. We previously mapped a major quantitative trait locus (QTL) (T2dm2sa) for impaired glucose tolerance on chromosome 2 and revealed that SM.A-T2dm2sa congenic mice showed not only glucose tolerance but also fat accumulation. In the present study, to identify the loci/genes that control the accumulation of abdominal fat, we performed QTL analyses of epididymal/mesenteric fat weight by using (A/J x SM.A-T2dm2sa)F2 mice in which the effect of T2dm2sa was excluded. As a result, two highly significant QTLs for mesenteric fat, as well as three significant QTLs for epididymal/mesenteric fat, were mapped on the different chromosomal regions. This suggests that the fat accumulations in individual fat depots are controlled by distinct genomic regions. Our comparison of these QTLs for abdominal fat distribution with those for glucose metabolism revealed that the major genetic factors affecting body fat distribution do not coincide with genetic factors affecting glucose metabolism in (A/J x SM.A-T2dm2sa)F2.

Fig. 1.

The chromosomal construction of SM.A-T2dm2sa congenic mice. The gray bar shows the SM/J-derived chromosomal region. The white bar shows the A/J-derived chromosomal region.

Fig. 2.

Logarithm of odds (LOD) score curves of highly significant or significant quantitative trait loci (QTLs) for abdominal fat weights. QTLs were detected for epididymal fat weight on chromosome (Chr.) 12 and 10, and for mesenteric fat weight on Chr. 7, 16, and 5. On Chr. 10, suggestive QTL for mesenteric fat was also detected. A bold line indicates an LOD score curve of epididymal fat. A dashed line indicates an LOD score curve of mesenteric fat.

Fig. 3.

Summary of quantitative trait loci (QTLs) for fat weights and diabetes-related traits in (A/J × SM.A-T2dm2sa)F2 mice. Solid arrows indicate highly significant or significant QTLs for epididymal fat weight and mesenteric fat weight that were mapped in this study, and significant QTLs for diabetes-related traits that were mapped in the previous study (20). Dashed arrows indicate suggestive QTLs. Blue QTLs, higher allele is SM/J; red QTLs, higher allele is A/J. Mfat, suggestive QTL for mesenteric fat; Efat, suggestive QTL for epididymal fat.