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

John N. Fain, Nobel A. Del Mar, Christopher A. Meade, Anton Reiner, Daniel Goldowitz

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

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 ∼ 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.

Original languageEnglish (US)
Pages (from-to)145-152
Number of pages8
JournalHuman molecular genetics
Volume10
Issue number2
StatePublished - Jan 15 2001

Fingerprint

Huntington Disease
Adipocytes
Transgenic Mice
Mutation
Aptitude
Adipose Tissue
Leptin
Obesity
Insulin
Isoproterenol
Serum
Fats
Glucose
High Fat Diet
Body Weight
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Abnormalities in the functioning of adipocytes from R6/2 mice that are transgenic for the Huntington's disease mutation. / Fain, John N.; Del Mar, Nobel A.; Meade, Christopher A.; Reiner, Anton; Goldowitz, Daniel.

In: Human molecular genetics, Vol. 10, No. 2, 15.01.2001, p. 145-152.

Research output: Contribution to journalArticle

Fain, John N. ; Del Mar, Nobel A. ; Meade, Christopher A. ; Reiner, Anton ; Goldowitz, Daniel. / Abnormalities in the functioning of adipocytes from R6/2 mice that are transgenic for the Huntington's disease mutation. In: Human molecular genetics. 2001 ; Vol. 10, No. 2. pp. 145-152.
@article{47403efa3ee94b24a20ae0c430881c34,
title = "Abnormalities in the functioning of adipocytes from R6/2 mice that are transgenic for the Huntington's disease mutation",
abstract = "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 ∼ 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.",
author = "Fain, {John N.} and {Del Mar}, {Nobel A.} and Meade, {Christopher A.} and Anton Reiner and Daniel Goldowitz",
year = "2001",
month = "1",
day = "15",
language = "English (US)",
volume = "10",
pages = "145--152",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Abnormalities in the functioning of adipocytes from R6/2 mice that are transgenic for the Huntington's disease mutation

AU - Fain, John N.

AU - Del Mar, Nobel A.

AU - Meade, Christopher A.

AU - Reiner, Anton

AU - Goldowitz, Daniel

PY - 2001/1/15

Y1 - 2001/1/15

N2 - 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 ∼ 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.

AB - 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 ∼ 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.

UR - http://www.scopus.com/inward/record.url?scp=0035862874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035862874&partnerID=8YFLogxK

M3 - Article

C2 - 11152662

AN - SCOPUS:0035862874

VL - 10

SP - 145

EP - 152

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 2

ER -