Evidence of impaired adipogenesis in insulin resistance.
To elucidate the roles of adipose tissue and skeletal muscle in the early development of insulin resistance, we characterized gene expression profiles of isolated adipose cells and skeletal muscle of non-diabetic insulin-resistant first-degree relatives of type 2 diabetic patients using oligonucleotide microarrays. About 600 genes and expressed sequence tags, which displayed a gene expression pattern of cell proliferation, were differentially expressed in the adipose cells. The differentially expressed genes in the skeletal muscle were mostly related to the cellular signal transduction and transcriptional regulation. To verify the microarray findings, we studied expression of genes participating in adipogenesis. The expression of Wnt signaling genes, WNT1, FZD1, DVL1, GSK3beta, beta-catenin, and TCF1, and adipogenic transcription factors, C/EBPalpha and beta and delta, PPARgamma, and SREBP-1, was reduced in the adipose tissue. The expression of adipose-specific proteins related to terminal differentiation, such as adiponectin and aP2, was reduced both in the adipose tissue and in the adipose cells isolated from portions of the biopsies. The adipose cells were enlarged in the insulin-resistant relatives and the cell size inversely correlated with the expression of the Wnt signaling genes, adiponectin, and aP2. Our findings suggest that insulin resistance is associated with an impaired adipogenesis.
Yang
Xiaolin
X
The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg SE-413 45, Sweden.
Jansson
Per-Anders
PA
Nagaev
Ivan
I
Jack
Maia M
MM
Carvalho
Eugenia
E
Sunnerhagen
Katharina Stibrant
KS
Cam
Margaret C
MC
Cushman
Samuel W
SW
Smith
Ulf
U
D017667:Adipocytes / Q000378:metabolism* / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D048429:Cell Size; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005192:Family Health; D020869:Gene Expression Profiling; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D051821:Lymphoid Enhancer-Binding Factor 1; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012044:Regression Analysis; D015398:Signal Transduction; D051822:T Cell Transcription Factor 1; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D051822:T Cell Transcription Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3