Insulin Sensitizing Effects of Vitamin D Mediated through Reduced Adipose Tissue Inflammation and Fibrosis

• DOI: 10.2337/db18-39-or
• Publication Date: 2018-06-22T18:57:33Z
• Authors: ERIC LONTCHI-YIMAGOU; SONA KANG; KEHAO ZHANG; AKANKASHA GOYAL; JEE YOUNG YOU; PREETI KISHORE; EVAN ROSEN; MEREDITH HAWKINS
• Keywords: Adipose tissue macrophages

Adipose tissue inflammation and fibrosis appear to be mediated by adipocytes contribute insulin resistance. Since vitamin D (25(OH)D) has anti-inflammatory anti-fibrotic effects, expression of its receptor in macrophages suggests that 25(OH)D signaling could mediate paracrine effects within adipose improve We performed a randomized, double-blinded placebo-controlled trial examine the repleting 25(OH)D-deficient (<20 ng/ml), resistant, overweight-to-obese humans (n=19). repletion >30 ng/ml was associated with reductions inflammatory (0.6-0.7-fold decreased TNF-α, IL-6, iNOS PAI-1) pro-fibrotic (0.4-0.8-fold TGF-β1, HiF1α, Collagen I, V, VI MMP7) genes, collagen immunofluorescence (19% reduction, p=0.02) improved hepatic sensitivity, assessed as suppression endogenous glucose production (EGP) during hyperinsulinemic clamp studies (1.28 ± 0.20 vs. 0.88 0.18 mg/kg/min, p=0.03). To determine whether D’s are through adipocytes, we studied an adipocyte-specific knockout mouse model (Adiponectin-Cre+VDR+/ fl) after 12 weeks on high fat diet. Despite no differences body weight or adiposity, VDR KO mice exhibited increased several pro-inflammatory (Tnf-α, iNos, Pai-1, Mcp-1 F4/80; 4-10 fold) genes (Tgf-β1, VI, Tsp1; 2-4 fold), concert resistance 2h (4 mU/kg/min)-euglycemic clamps (EGP 10 3 2 mg/kg/min WT, p = 0.021). These human rodent establish beneficial role restraining well resistance, suggest normalizing levels have metabolic benefits targeted individuals. Disclosure E. Lontchi-Yimagou: None. S. Kang: K. Zhang: A. Goyal: J. You: P. Kishore: Rosen: M. Hawkins: