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 regulation (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 severe wasting beginning at approximately 12 weeks of age and die between 12 and 15 weeks. Despite an overall growth retardation compared with wild-type littermates, we observed an enhanced accumulation of body fat at 8-9 weeks of age in R6/2 mice fed laboratory chow or a synthetic high fat, high sugar diet. 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. As expected, the obesity in the high fat, high sugar-fed R6/2 mice was accompanied by increased serum leptin. The ability of insulin to stimulate leptin 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 of 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.
Fain
J N
JN
Departments of Molecular Sciences and Anatomy and Neurobiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA. jfain@utmem.edu
Del Mar
N A
NA
Meade
C A
CA
Reiner
A
A
Goldowitz
D
D
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D046508:Culture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004822:Epididymis / Q000033:anatomy & histology; D005938:Glucocorticoids / Q000494:pharmacology; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D020738:Leptin / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005938:Glucocorticoids; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D007328:Insulin; D020738:Leptin; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D003907:Dexamethasone; D007545:Isoproterenol