Adipocyte Hypertrophy, Inflammation and Fibrosis Characterize Subcutaneous Adipose Tissue of Healthy, Non-Obese Subjects Predisposed to Type 2 Diabetes

• Published in: PloS one Vol. 9; no. 8; p. e105262
• Main Authors: Henninger, A. M. Josefin, Eliasson, Björn, Jenndahl, Lachmi E., Hammarstedt, Ann
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.08.2014; Public Library of Science (PLoS)
• Subjects: Adipocytes; Adipocytes - cytology; Adipocytes - metabolism; Adipogenesis; Adipogenesis - genetics; Adipose tissue; Adult; Biology and Life Sciences; Blood Glucose; Body fat; Body mass; Body Mass Index; Cell Differentiation; Cell Enlargement; Cell size; Chronology; complications; cytology; Development and progression; Diabetes Mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - etiology; Diabetes therapy; Disease Susceptibility; Endocrinology and Diabetes; Endokrinologi och diabetes; etiology; Female; Fibrosis; Gene Expression; Genetic Predisposition to Disease; genetics; Glucose; Glucose tolerance; Glucose tolerance test; Hip; Humans; Hypertrophy; Inflammation; Inflammation - complications; Inflammation - genetics; Insulin; Insulin - metabolism; Insulin resistance; Laboratories; Male; Medicine and Health Sciences; metabolism; Middle Aged; Obesity; pathology; Risk Factors; Sensitivity; Subcutaneous Fat; Subcutaneous Fat - metabolism; Subcutaneous Fat - pathology; Triglycerides; Type 2; Type 2 diabetes; Wnt protein; Wnt Signaling Pathway; United States > US; Sweden
• DOI: 10.1371/journal.pone.0105262
• ISSN: 1932-6203

The adipose tissue is important for development of insulin resistance and type 2 diabetes and adipose tissue dysfunction has been proposed as an underlying cause. In the present study we investigated presence of adipocyte hypertrophy, and gene expression pattern of adipose tissue dysfunction in the subcutaneous adipose tissue of healthy, non-obese subjects predisposed to type 2 diabetes compared to matched control subjects with no known genetic predisposition for type 2 diabetes. Seventeen healthy and non-obese subjects with known genetic predisposition for type 2 diabetes (first-degree relatives, FDRs) and 17 control subjects were recruited. The groups were matched for gender and BMI and had similar age. Glucose tolerance was determined by an oral glucose tolerance test and insulin sensitivity was calculated using HOMA-index. Blood samples were collected and subcutaneous abdominal adipose tissue biopsies obtained for gene expression analysis and adipocyte cell size measurement. Our findings show that, in spite of similar age, BMI and percent body fat, FDRs displayed adipocyte hypertrophy, as well as higher waist/hip ratio, fasting insulin levels, HOMA-IR and serum triglycerides. Adipocyte hypertrophy in the FDR group, but not among controls, was associated with measures of impaired insulin sensitivity. The adipocyte hypertrophy was accompanied by increased inflammation and Wnt-signal activation. In addition, signs of tissue remodeling and fibrosis were observed indicating presence of early alterations associated with adipose tissue dysfunction in the FDRs. Genetic predisposition for type 2 diabetes is associated with impaired insulin sensitivity, adipocyte hypertrophy and other markers of adipose tissue dysfunction. A dysregulated subcutaneous adipose tissue may be a major susceptibility factor for later development of type 2 diabetes.