We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Search for the Causal Genes of Obesity-Induced Insulin Resistance by Analyzing the Expression Profile in Human Adipose Tissues.
- Authors
Okazaki, Yukiko; Ueki, Kohjiro; Hara, Kazuo; Horikoshi, Momoko; Kadowaki, Takashi
- Abstract
Type 2 diabetes and the metabolic syndrome, are explosively increasing due to a pandemic of obesity. Numerous studies using animal models have suggested that hypertrophied adipocytes by obesity produce a wide variety of adipokines, which may cause and enhance insulin resistance and atherosclerosis. However, it remains unclear whether these results are recapitulated and what adipokines are causative for the metabolic syndrome in human. In the present study, we have extensively analyzed the expression profiles in adipose tissues of Japanese non-diabetic subjects with various body mass indexes. Fifty-one subjects, who were taken subcutaneous fat samples in the plastic surgery, participated in this study. The isolated RNA from the adipose tissue was applied to an expression analysis using a microarray chip (Affymetrix Human Genome U 133 Plus 2). Together with the clinical data, expression analysis revealed that there are 75 genes whose expression was increased more than 2 fold in overweight (OW) group (BMI≧22) compared to normal weight (NW) group (BMI<22), while 100 genes were decreased in expression more than 2 fold in OW compared to NW. These contain many genes, which seem to encode the secretory proteins including proinflammatory cytokines, Wnt family proteins and TGFβ super-family proteins. Indeed, there were strong correlations between BMI and expression levels of some adipokines, such as leptin, IL-8, IL-18 and MCP-1, whereas an inverse correlation was observed between BMI and adiponectin expression. On the other hand, very interestingly, most of the genes for mitochondrial function, such as electron transport, were decreased in expression in insulin resistant (IR) group (HOMA-IR≧ 1.5) compared to insulin sensitive (IS) group (HOMA-IR< 1.5), although the reduction of each gene expression (IR vs. IS) was too small (20-30%) to reach statistical significance. Since the subjects in the current study are not diabetic or morbidly obese, it is very likely that the moderate mitochondrial dysfunction assumed by the results of microarray data in this study may play a causative role in insulin resistance. Thus, it is important to explore what genetically and environmentally makes this change. Furthermore, some of the adipokines, whose expression was altered at the very early stage of obesity in this study, may also contribute to the development of the metabolic syndrome.
- Publication
Diabetes, 2007, Vol 56, pA286
- ISSN
0012-1797
- Publication type
Academic Journal