Insulin-sensitizing effects of vitamin D repletion mediated by adipocyte vitamin D receptor: Studies in humans and mice

• DOI: 10.1016/j.molmet.2020.101095
• Publication Date: 2020-10-10T05:33:36Z
• Authors: Eric Lontchi-Yimagou; Sona Kang; Akankasha Goyal; Kehao Zhang; Jee Y. You; Michelle Carey; Swati Jain; Shobhit Bhansali; Sylvia Kehlenbrink; Peng Guo; Evan D. Rosen; Preeti Kishore; Meredith Hawkins
• Keywords: Adipose tissue macrophages

Adipose tissue inflammation and fibrosis appear to contribute insulin resistance in obesity. Vitamin D receptor (Vdr) genes are expressed by adipocytes, macrophages, fibroblasts, all of which could potentially play a role adipose fibrosis. As vitamin has been shown have direct anti-inflammatory effects on we determined whether specific receptor-mediated adipocytes impact ultimately resistance. We examined the repleting 25(OH)D-deficient, resistant, overweight-to-obese human subjects (n = 19). A comprehensive assessment whole-body action was undertaken with stepped euglycemic (∼90 mg/dL) hyperinsulinemic clamp studies both before after administration or placebo. were quantified real-time rt-PCR immunofluorescence subcutaneous abdominal tissue. To determine D's mediated through conducted (4 mU/kg/min) analysis using an adipocyte-specific knockout (VDR-KO) mouse model (adiponectin-Cre + VDR+/fl) following high-fat diet feeding for 12 weeks. 25(OH)D repletion associated reductions expression pro-inflammatory pro-fibrotic genes, decreased collagen immunofluorescence, improved hepatic sensitivity humans. Worsening trends six months placebo suggest progressive metabolic deficiency. Ad-VDR-KO mice mirrored D-deficient humans, displaying increased These complementary rodent support beneficial improving reducing targeted individuals, likely via adipocytes. far-reaching implications understanding mediating impacting sensitivity.