Markers of remodeling in subcutaneous adipose tissue are strongly associated with overweight and insulin sensitivity in healthy non-obese men

Background Alteration in extracellular matrix (ECM) in adipose tissues (AT) has been associated with insulin resistance, diabetes and obesity. Aim To investigate whether selected biomarkers of ECM remodeling in AT associate with the amount and distribution of abdominal AT and with insulin sensitivity and other glucometabolic variables. Materials and Methods Subcutaneous AT and fasting blood samples were collected in 103 middle-aged healthy non-obese men. Gene expression in AT was determined by RT-PCR and distribution of AT by computed tomography, separated into subcutaneous, deep subcutaneous and visceral AT. Circulating levels were determined by ELISA, and insulin sensitivity was measured by glucose clamp technique, assessing glucose disposal rate (GDR). Results Metalloproteinase (MMP)-9, tissue inhibitor of MMP (TIMP)-1 and plasminogen activator inhibitor (PAI)-1 expression in AT correlated significantly to the amount of AT in all compartments (r s =0.41-0.53, all p ≤0.01), and to insulin sensitivity, insulin, C-peptide, waist circumference and body mass index (BMI) (r s =0.25–0.57, all p ≤0.05). When dichotomizing the glucometabolic variables at median levels the expression of MMP-9 was 5.3 fold higher in subjects with insulin sensitivity below median (GDR<6.3mg/kg/min) ( p =0.002) and 3.1 fold higher in subjects with BMI above median level (>23.5kg/m 2 ) ( p =0.013). Galectin-3 did not associate with the amount of AT, but inversely with insulin and c.peptide ((p<0.01m both). Conclusion In our healthy non-obese middle-aged population AT-expressed genes, central in remodeling of ECM, associated strongly with the amount of abdominal AT, overweight and insulin sensitivity, indicating AT-remodeling to be important also in non-obese individuals. The remodeling process seems furthermore to play a central role for glucometabolic disturbances.