title: 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 because of multidrug resistance. Previous work established that vitamin D induces macrophage antimicrobial functions against Mycobacterium tuberculosis. In this article, 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 proadipogenic peroxisome proliferator-activated receptor γ (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 the potential for host-based, adjunct antituberculosis therapy targeting lipid metabolism.
authors.affiliation: Knowledge Synthesis Inc., 725 Folger Avenue, Berkeley, CA 94710.
authors.forename: Hugh
authors.initials: H
authors.lastname: Salamon
authors.affiliation: Public Health Research Institute and Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ 07103.
authors.forename: Natalie
authors.initials: N
authors.lastname: Bruiners
authors.affiliation: Public Health Research Institute and Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ 07103.
authors.forename: Karim
authors.initials: K
authors.lastname: Lakehal
authors.affiliation: Public Health Research Institute and Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ 07103.
authors.forename: Lanbo
authors.initials: L
authors.lastname: Shi
authors.affiliation: Public Health Research Institute and Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ 07103.
authors.forename: Janani
authors.initials: J
authors.lastname: Ravi
authors.affiliation: Knowledge Synthesis Inc., 725 Folger Avenue, Berkeley, CA 94710.
authors.forename: Ken D
authors.initials: KD
authors.lastname: Yamaguchi
authors.affiliation: Public Health Research Institute and Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ 07103.
authors.forename: Richard
authors.initials: R
authors.lastname: Pine
authors.affiliation: Public Health Research Institute and Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ 07103.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Gennaro
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects* / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D047495:PPAR gamma / Q000276:immunology; D018167:Receptors, Calcitriol / Q000276:immunology; D059467:Transcriptome / Q000187:drug effects* / Q000276:immunology; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D014807:Vitamin D / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D047495:PPAR gamma; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014815:Vitamins; D014807:Vitamin D