Conclusion
These results are consistent with basic science data, suggesting that COL6A3 might contribute to adipose tissue inflammation.
Methods
Adipose tissue biopsies were obtained from a cross-sectional study (n = 109), an overfeeding study (n = 9), and a pioglitazone treatment study (n = 14). Adipose tissue gene expression was measured by quantitative RT-PCR, immunohistochemistry, and adipocyte sizing by fixation with osmium and Coulter counting. Body composition was measured by dual-energy x-ray absorptiometry and visceral adipose tissue by computed tomography. Patients with high or low COL6A3 mRNA were compared by one-way ANOVA.
Results
In humans, immunohistochemistry revealed that COL6 is present in adipose tissue extracellular matrix. COL6A3 mRNA is correlated with body mass index (r = 0.60, P < 0.0001) and fat mass (r = 0.41, P < 0.0001). COL6A3 expression was similar in obese vs. type 2 diabetes patients. Obese subjects with high COL6A3 mRNA had greater visceral adipose tissue mass (P < 0.05), lower size of small and medium adipocytes (P < 0.05), more CD68+ and CD163/MAC2+ macrophages, and increased macrophage inflammatory protein-1alpha and macrophage chemoattractant protein-1alpha mRNA (P < 0.05). Eight weeks of overfeeding increased body weight and COL6A3 mRNA (P < 0.05). Pioglitazone decreased COL6A3 mRNA, and the change was inversely proportional to baseline COL6A3 mRNA (r = -0.95, P < 0.0001).