Scientific Session I, Cardiovascular, Endocrinology/Metabolism, 8.30AM – 10.30AM
1: VITAMIN D REPLETION REDUCES ADIPOSE TISSUE FIBROSIS AND IMPROVES INSULIN SENSITIVITY
Internal Medicine, Albert Einstein College of Medicine, Bronx, NY
Purpose of Study Adipose tissue fibrosis has been implicated as a contributing factor to insulin resistance and adipose inflammation in obesity. Vitamin D (vit D) has been shown to reduce fibrosis in other tissue types by inhibiting pro-fibrotic processes and collagen synthesis. Thus we hypothesized that vit D repletion could reduce adipose tissue fibrosis and improve insulin sensitivity.
Methods Used In a randomized, double-blind, placebo-controlled trial, stepped euglycemic, hyperinsulinemic (30 and 80 mU/m2/min) clamp studies were performed in 19 obese and insulin resistant human subjects with vit D deficiency (∼13 ng/ml) to quantify endogenous glucose production (EGP) and glucose uptake (GU) before and after placebo or sufficient vit D therapy to normalize vit D levels (>30 ng/ml).
Summary of Results After vit D repletion, we observed that expression of the pro-fibrotic genes TGF-β1, HiF1α, Collagen I, V, VI and MMP7 in whole fat decreased by 0.81, 0.72, 0.56, 0.56, 0.43, and 0.62-fold, respectively (all p<0.05). Collagen I immunofluorescence decreased by 61% (p=0.04). In addition, adipose tissue inflammation also decreased significantly with 0.67, 0.61, 0.71 and 0.70-fold decreases of expression of the following pro-inflammatory factors: TNF-α, IL-6, iNOS and PAI-1 (all p<0.05). The expression of the same pro-inflammatory factors in adipose tissue macrophages also decreased by 0.44, 0.32, 0.53 and 0.70-fold, respectively (all p<0.05). Importantly, these findings were associated with a 24% greater ability of insulin to suppress EGP (p=0.04). GU, however, did not show significant change. In the placebo group, there were no significant changes in expression of pro-fibrotic or pro-inflammatory genes (all p>0.05), although there was an intriguing trend toward worsening fibrosis and inflammation as well as hepatic insulin resistance when followed for 6 months. …