Intrinsic heterogeneity in adipose tissue of fat-specific insulin receptor knock-out mice is associated with differences in patterns of gene expression

被引:71
作者
Blüher, M
Patti, ME
Gesta, S
Kahn, BB
Kahn, CR
机构
[1] Joslin Diabet Ctr, Boston, MA 02215 USA
[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA
[3] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrine, Diabet Unit, Boston, MA 02215 USA
关键词
D O I
10.1074/jbc.M404569200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mice with a fat-specific insulin receptor knock-out (FIRKO) have reduced adipose tissue mass, are protected against obesity, and have an extended life span. White adipose tissue of FIRKO mice is also characterized by a polarization into two major populations of adipocytes, one small (< 50 mu m) and one large (> 100 mum), which differ with regard to basal triglyceride synthesis and lipolysis, as well as in the expression of fatty acid synthase, sterol regulatory element-binding protein 1c, and CCAAT/enhancer-binding protein alpha (C/EBP-alpha). Gene expression analysis using RNA isolated from large and small adipocytes of FIRKO and control (IR lox/lox) mice was performed on oligonucleotide microarrays. Of the 12,488 genes/expressed sequence tags represented, 111 genes were expressed differentially in the four populations of adipocytes at the p < 0.001 level. These alterations exhibited 10 defined patterns and occurred in response to two distinct regulatory effects. 63 genes were identified as changed in expression depending primarily upon adipocyte size, including C/EBP-alpha, C/EBP-delta, superoxide dismutase 3, and the platelet-derived growth factor receptor. 48 genes were regulated primarily by impairment of insulin signaling, including transforming growth factor beta, interferon gamma, insulin-like growth factor I receptor, activating transcription factor 3, aldehyde dehydrogenase 2, and protein kinase C delta. These data suggest an intrinsic heterogeneity of adipocytes with differences in gene expression related to adipocyte size and insulin signaling.
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页码:31891 / 31901
页数:11
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