1: VITAMIN D REPLETION REDUCES ADIPOSE TISSUE FIBROSIS AND IMPROVES INSULIN SENSITIVITY

Jee Young You*

Eric Lontchi-Yimagou

Swati Jain

Kehao Y. Zhang

Akankasha Goyal

Preeti Kishore

Meredith Hawkins

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. …