Abnormalities in the functioning of adipocytes from R6/2 mice that are transgenic for the Huntington's disease mutation

In an effort to characterize the basis of abnormalities in body weight regu lation (i.e, wasting) in Huntington's disease (HD), we examined adipocytes in a transgenic model of HD, the R6/2 mouse, These mice typically show seve re wasting beginning at similar to 12 weeks of age and die between 12 and 1 5 weeks. Despite an overall growth retardation compared with wild-type litt ermates, we observed an enhanced accumulation of body fat at 8-9 weeks of a ge in R6/2 mice fed laboratory chow or a synthetic high fat, high sugar die t, The obesity was not accompanied by symptoms associated with diabetes, as there were no abnormalities in serum glucose, serum insulin or the ability of insulin to stimulate glucose metabolism in epididymal adipose tissue, A s expected, the obesity in the high fat, high sugar-fed R6/2 mice was accom panied by increased serum leptin, The ability of insulin to stimulate lepti n release from isolated epididymal adipose tissue was also enhanced in R6/2 mice, In contrast, the ability of isoproterenol to inhibit leptin release was reduced in adipose tissue from R6/2 mice, as was the lipolytic effect o f isoproterenol, These data suggest that the obesity observed at 8-9 weeks in R6/2 mice may stem from a defect in fat breakdown by adipocytes.