Vitamin D3/VDR resists diet-induced obesity by modulating UCP3 expression in muscles

Journal of Biomedical Science

Research

Tetsuya Tagami¹  Takashi Miyawaki²  Yuki Fukuda³  Rie Koyama³  Kumi Futawaka³  Misa Hayashi³  Kenji Moriyama⁴  Yue Fan⁵  Miyuki Imamoto⁶  Masato Kasahara⁶ 

[1] Clinical Research Institute for Endocrine and Metabolic Diseases, National Hospital Organization Kyoto Medical Center, 612-8555, Kyoto, Japan;Department of Food and Nutrition, Kyoto Women’s University, 605-8501, Kyoto, Japan;Department of Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 663-8179, Hyogo, Japan;Department of Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 663-8179, Hyogo, Japan;Department of Nephrology and Blood Purification, Institute of Biomedical Research and Innovation, Kobe Medical Frontier Center, 650-0047, Kobe, Japan;Clinical Research Institute for Endocrine and Metabolic Diseases, National Hospital Organization Kyoto Medical Center, 612-8555, Kyoto, Japan;Department of Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 663-8179, Hyogo, Japan;School of Chinese Materia Medica, Beijing University of Chinese Medicine, 100102, Beijing, China;Department of Nephrology and Blood Purification, Institute of Biomedical Research and Innovation, Kobe Medical Frontier Center, 650-0047, Kobe, Japan;

关键词: VDRE;    Transcription;    Promoter;   

DOI  :  10.1186/s12929-016-0271-2

 received in 2016-02-22, accepted in 2016-07-11,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsEight-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.ResultsMice 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.ConclusionWe suggest that VD3/VDR inhibits weight gain by activating UCP3 in the muscles.

【 授权许可】

CC BY   
© The Author(s). 2016