title: Induction of STEAP4 correlates with 1,25-dihydroxyvitamin D3 stimulation of adipogenesis in mesenchymal progenitor cells derived from human adipose tissue.
abstract: The vitamin D receptor (VDR) is expressed in human adipocytes and is transiently induced during early adipogenesis in mesenchymal progenitor cell models. VDR null mice exhibit enhanced energy expenditure and reduced adiposity even when fed high fat diets. Adipocyte-specific transgenic-expression of human VDR in mice enhances adipose tissue mass, indicating that VDR activation in adipocytes enhances lipid storage in vivo. In these studies, we conducted genomic profiling and differentiation assays in primary cultures of human adipose-derived mesenchymal progenitor cells to define the role of the VDR and its ligand 1,25-dihydroxyvitamin D3 (1,25D) in adipogenesis. In the presence of adipogenic media, 1,25D promoted lipid accumulation and enhanced the expression of FABP4, FASN, and PPARγ. Mesenchymal cells derived from 6-month old VDR null mice exhibited impaired adipogenesis ex vivo but differentiation was restored by stable expression of human VDR. STEAP4, a gene that encodes a metalloreductase linked to obesity, insulin sensitivity, metabolic homeostasis and inflammation, was highly induced in human adipose cells differentiated in the presence of 1,25D but was minimally affected by 1,25D in undifferentiated precursors. These studies provide a molecular basis for recent epidemiological associations between vitamin D status, body weight and insulin resistance which may have relevance for prevention or treatment of metabolic syndrome and obesity.
authors.affiliation: Department of Biomedical Sciences, University at Albany, Albany, NY 12144, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Narvaez
authors.forename: K M
authors.initials: KM
authors.lastname: Simmons
authors.forename: J
authors.initials: J
authors.lastname: Brunton
authors.forename: A
authors.initials: A
authors.lastname: Salinero
authors.forename: S V
authors.initials: SV
authors.lastname: Chittur
authors.forename: J E
authors.initials: JE
authors.lastname: Welsh
mesh_terms: D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D000818:Animals; D001835:Body Weight / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D008565:Membrane Proteins; D047495:PPAR gamma; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D010088:Oxidoreductases; C503310:STEAP4 protein, human; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I