Combined effects of insulin treatment and adipose tissue-specific agouti expression on the development of obesity

被引:56
作者
Mynatt, RL
Miltenberger, RJ
Klebig, ML
Zemel, MB
Wilkinson, JE
Wilkison, WO
Woychik, RP
机构
[1] OAK RIDGE NATL LAB,DIV BIOL,OAK RIDGE,TN 37831
[2] UNIV TENNESSEE,DEPT NUTR,KNOXVILLE,TN 37996
[3] UNIV TENNESSEE,COLL VET MED,DEPT PATHOL,KNOXVILLE,TN 37901
[4] GLAXO WELLCOME INC,RES TRIANGLE PK,NC 27709
基金
英国惠康基金;
关键词
transgenic mice; diabetes;
D O I
10.1073/pnas.94.3.919
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The agouti gene product is a secreted protein that acts in a paracrine manner to regulate coat color in mammals, Several dominant mutations at the agouti locus in mice cause the ectopic, ubiquitous expression of agouti, resulting in a condition similar to adult-onset obesity and non-insulin-dependent diabetes mellitus, The human agouti protein is 85% homologous to mouse agouti; however, unlike the mouse agouti gene, human agouti is normally expressed in adipose tissue, To address whether expression of agouti in human adipose tissue is physiologically relevant, transgenic mice were generated that express agouti in adipose tissue. Similar to most humans, these mice do not become obese or diabetic, However, we found that daily insulin injections significantly increased weight gain in the transgenic lines expressing agouti in adipose tissue, but not in nontransgenic mice, These results suggest that insulin triggers the onset of obesity and that agouti expression in adipose tissue potentiates this effect, Accordingly, the investigation of agouti's role in obesity and non-insulin-dependent diabetes mellitus in mice holds significant promise for understanding the pathophysiology of human obesity.
引用
收藏
页码:919 / 922
页数:4
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