Cutting Edge: Vitamin D Regulates Lipid Metabolism in Mycobacterium tuberculosis Infection

Abstract

Vitamin D has long been linked to resistance to tuberculosis, an infectious respiratory disease that is increasingly hard to treat due to multidrug resistance. Previous work established that vitamin D induces macrophage antimicrobial functions against Mycobacterium tuberculosis. Here we report a novel, metabolic role for vitamin D in tuberculosis identified through integrated transcriptome and mechanistic studies. Transcriptome analysis revealed an association between vitamin D receptor (VDR) and lipid metabolism in human tuberculosis and infected macrophages. Vitamin D treatment of infected macrophages abrogated infection-induced accumulation of lipid droplets, which are required for intracellular M. tuberculosis growth. Additional transcriptomics results showed that vitamin D downregulates the pro-adipogenic peroxisome proliferator-activated receptor gamma (PPARγ) in infected macrophages. PPARγ agonists reversed the antiadipogenic and the antimicrobial effects of VDR, indicating a link between VDR- and PPARγ-signaling in regulating both vitamin D functions. These findings suggest potential for host-based, adjunct antituberculosis therapy targeting lipid metabolism.

Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation

“…Lysolipids are phospholipids that have had one or more acyl group removed (by hydrolysis). Vitamin D has multiple effects on lipid metabolism through its actions on nuclear hormone receptors, such as the vitamin D receptor and PPARγ (30), including changing the phospholipid content of cells (31). Thus, our results are consistent with the effects of vitamin D on lipid metabolism mediated through these receptors.…”

Vitamin D, leptin and impact on immune response to seasonal influenza A/H1N1 vaccine in older persons

“…42 Several in vitro studies have recently demonstrated that VDR and PPAR-g signaling pathways interact and there is evidence of "crosstalk," although the detailed mechanisms have not been elucidated. 42,44,45 In one study, PPAR-g was found to monopolize RXR-a available for VDR binding and there was an inverse relationship between VDR and PPARg basal expression in these cell lines. 44 The promotor region of certain human PPAR genes contains a potent VDRE (vitamin D response element).…”

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“…A study has shown that M. tuberculosis infected macrophages differentiate into lipid rich foam cells by accumulating lipid droplets that are required for its intracellular growth [48,49] . Another recent study reported that vitamin D 3 treatment inhibited the accumulation of lipid droplets in infected macrophages by downregulating the expression of proadipogenic peroxisome proliferator-activated receptor-γ (PPAR-γ) and control the growth of intracellular M. tuberculosis [50] .…”