title: Vitamin D3/VDR resists diet-induced obesity by modulating UCP3 expression in muscles.
abstract: BACKGROUND
  The impact of vitamin D3 (VD3) on obesity has been reported in the past. Our study was aimed at investigating the possible mechanisms by which VD3 affects obesity induced by a high fat diet.
  
  
  METHODS
  Eight-week-old C57BL/6 J male mice were fed a normal- or high-fat diet for 9 weeks and were treated with a gavage of vehicle (corn oil) or cholecalciferol (50 μg/kg, daily). Body weight, white adipose tissue weight, blood lipid and glucose levels were measured. In addition, we investigated the expression of 1,25(OH)2D3 (calcitriol)/VDR-regulated genes involved in energy and lipid metabolism, such as of uncoupling protein 3 (UCP3), by using qRT-PCR in the liver, adipose tissue, skeletal muscle and C2C12, L6, and H-EMC-SS cells. We also measured UCP3 promoter transcription in the same cell lines using a Dual Luciferase Assay. Furthermore, we analyzed the binding site consensus sequences of VDR on the UCP3 promoter.
  
  
  RESULTS
  Mice consuming a high-fat diet treated with cholecalciferol had lower body weight and adipose tissue weight and higher expression of UCP3 compared to the other treatment groups. Changes in the expression of genes correlated with calcitriol/VDR. Luciferase activity was dose-dependently associated with calcitriol/VDR levels. We confirmed the functional VDR binding site consensus sequences at -2200, -1561, -634, and +314 bp in the UCP3 promoter region.
  
  
  CONCLUSIONS
  We suggest that VD3/VDR inhibits weight gain by activating UCP3 in the muscles.
authors.affiliation: Department of Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, 663-8179, Japan.|School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100102, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, 663-8179, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Futawaka
authors.affiliation: Department of Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, 663-8179, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Koyama
authors.affiliation: Department of Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, 663-8179, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fukuda
authors.affiliation: Department of Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, 663-8179, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Nephrology and Blood Purification, Institute of Biomedical Research and Innovation, Kobe Medical Frontier Center, Kobe, 650-0047, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Imamoto
authors.affiliation: Department of Food and Nutrition, Kyoto Women's University, Kyoto, 605-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyawaki
authors.affiliation: Department of Nephrology and Blood Purification, Institute of Biomedical Research and Innovation, Kobe Medical Frontier Center, Kobe, 650-0047, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kasahara
authors.affiliation: Clinical Research Institute for Endocrine and Metabolic Diseases, National Hospital Organization Kyoto Medical Center, Kyoto, 612-8555, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tagami
authors.affiliation: Department of Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, 663-8179, Japan. kemori@mukogawa-u.ac.jp.|Department of Nephrology and Blood Purification, Institute of Biomedical Research and Innovation, Kobe Medical Frontier Center, Kobe, 650-0047, Japan. kemori@mukogawa-u.ac.jp.|Clinical Research Institute for Endocrine and Metabolic Diseases, National Hospital Organization Kyoto Medical Center, Kyoto, 612-8555, Japan. kemori@mukogawa-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Moriyama
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002762:Cholecalciferol / Q000494:pharmacology*; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D000071247:Uncoupling Protein 3 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004041:Dietary Fats; D009124:Muscle Proteins; D018167:Receptors, Calcitriol; C000604393:Ucp3 protein, mouse; D000071247:Uncoupling Protein 3; D002762:Cholecalciferol; D002117:Calcitriol
keywords: Promoter; Transcription; VDRE