Vitamin D3 supplementation decreases a unique circulating monocyte cholesterol pool in patients with type 2 diabetes

•Vitamin D is first intervention to reduce monocyte cholesterol in type 2 diabetes.•Vitamin D replacement decreases monocyte CD36 expression and cholesterol uptake.•Vitamin D is a monocyte ER stress reliever in type 2 diabetes. Cross-sectional studies indicate consistent associations between low 25(...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of steroid biochemistry and molecular biology 2018-03, Vol.177, p.187-192
Main Authors: Riek, Amy E., Oh, Jisu, Darwech, Isra, Worthy, Veronica, Lin, Xiaobo, Ostlund, Richard E., Zhang, Rong M., Bernal-Mizrachi, Carlos
Format: Article
Language:English
Subjects:
Atherosclerosis
CD36
Cholesterol metabolism
Monocytes
Vitamin D
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•Vitamin D is first intervention to reduce monocyte cholesterol in type 2 diabetes.•Vitamin D replacement decreases monocyte CD36 expression and cholesterol uptake.•Vitamin D is a monocyte ER stress reliever in type 2 diabetes. Cross-sectional studies indicate consistent associations between low 25(OH)D concentration and increased risk of cardiovascular disease (CVD), but results of randomized control trials (RCTs) are mixed. However, the majority of the RCTs do not focus on type 2 diabetics, potentially obscuring the effects of vitamin D in this population. In vitro 1,25(OH)2D3 downregulates macrophage cholesterol deposition, but the in vivo effects are unknown. To explore potential mechanisms of the effects of vitamin D on CVD risk in patients with type 2 diabetes, we isolated monocytes in a subset of 26 patients from our RCT of diabetics with baseline serum 25(OH)D 50% reduction in the vitamin D group with no change in the placebo group. This was mediated through suppression of endoplasmic reticulum stress and scavenger receptor CD36 protein expression. The reduction in monocyte cholesterol uptake was reflected in a 19% decrease in total monocyte cholesterol content. Interestingly, cross-sectional analysis of circulating monocytes from vitamin D-deficient vs. sufficient diabetic patients revealed 8-fold higher cholesteryl ester content, confirming the capacity of these monocytes to uptake and carry cholesterol in the circulation. This study identifies a unique circulating cholesterol pool within monocytes that is modulated by vitamin D and has the potential to contribute to CVD in type 2 diabetes.
ISSN:0960-0760
1879-1220
DOI:10.1016/j.jsbmb.2017.09.011