Association of Omental Adipocyte Hypertrophy and Fibrosis with Human Obesity and Type 2 Diabetes.

Abstract

Morphological alterations including adipocyte hypertrophy and fibrosis deposition are important surrogate markers of visceral adipose tissue function, but the relationships between these morphological changes and type 2 diabetes mellitus (T2DM) and impaired insulin sensitivity are poorly defined. Omental adipose tissue was obtained from 66 individuals with obesity but without T2DM (OB group), 93 individuals with both obesity and T2DM (T2DM group), and 15 individuals with normal BMI and normal glucose tolerance (NGT group). Adipocyte diameter and volume were measured through pathological section analysis. Pericellular and perilobular fibrosis was determined through picrosirius red staining and immunochemistry, while fibrosis-related genes were tested through gene expression and hydroxyproline content. Compared with the NGT and OB groups, individuals from the T2DM group displayed increased adipocyte diameter and volume levels. Increased adipocyte size (diameter and volume) was positively associated with hyperglycemia and insulin resistance and inversely correlated with insulin sensitivity (using the Matsuda whole-body insulin sensitivity index assessment of insulin sensitivity) and β-cell function (disposition index 30 and disposition index 120). The fibrosis levels of the OB group were the highest out of the three groups, whereas the fibrosis levels of T2DM individuals were lower than the OB group but higher than the NGT group. Although fibrosis was negatively correlated with T2DM, fibrosis deposition was not remarkably associated with impaired systemic insulin sensitivity and glucose metabolism. Compared with fibrosis deposition, adipocyte hypertrophy is more closely associated with T2DM and impaired systemic insulin sensitivity.