Abstract
Vitamin D status has been implicated in obesity and adipose tissue inflammation. In the present study, we explored the effects of dietary vitamin D supplementation on adipose tissue inflammation and immune cell population, and the effects of in vitro 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) treatment on pro-inflammatory cytokine production by stromal vascular cells (SVCs) and adipocytes in lean and high-fat diet-induced obese mice. The results show that epididymal fat Mcp-1 and Rantes mRNA levels, which were higher in obese mice compared with lean mice, were significantly down-regulated by vitamin D supplementation. While obese mice had higher numbers of macrophages and natural killer (NK) cells within adipose tissue, these remained unaltered by vitamin D supplementation. In accordance with these in vivo findings, the in vitro 1,25(OH)2D3 treatment decreased IL-6, MCP-1, and IL-1β production by SVCs from obese mice, but not by adipocytes. In addition, 1,25(OH)2D3 treatment significantly decreased Tlr2 expression and increased mRNA levels of Iκba and Dusp1 in SVCs. These findings suggest that vitamin D supplementation attenuates inflammatory response in adipose tissue, especially in SVCs, possibly through inhibiting NF-κB and MAPK signaling pathways in SVCs but not by the inhibition of macrophage infiltration.
Highlights
The prevalence of obesity and related disorders are increasing worldwide
Several in vitro studies have shown that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment could alleviate inflammatory responses in mouse or human adipocytes [9,10]
We evaluated whether dietary vitamin D supplementation would affect inflammatory responses and the subpopulation of immune cells in adipose tissue using high-fat diet-induced obese and lean mice
Summary
Adipose tissue expansion or fat accumulation in the liver, observed with obesity, activates the pro-inflammatory signaling pathway, which mediates pathogenesis of metabolic disorders, such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) [1,2,3,4]. Hypovitaminosis D is often observed in obese humans [5]. (1,25(OH)2D3) treatment could alleviate inflammatory responses in mouse or human adipocytes [9,10]. Adipose tissue, composed of adipocytes and non-adipocytes known as stromal vascular cells (SVCs), functions as an energy reservoir and as a mediator for immune and inflammatory responses by releasing more than 260 proteins [11,12]. Obesity leads to hypertrophic adipose expansion, which triggers the recruitment of inflammatory immune cells and the secretion of pro-inflammatory
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