Bidirectional effect of vitamin D on brown adipogenesis of C3H10T1/2 fibroblast-like cells

• Published in: PeerJ (San Francisco, CA) CA), 2023-01, Vol.11, p.e14785-e14785, Article e14785
• Main Authors: Mukai, Takako, Kusudo, Tatsuya
• Format: Article
• Language: English
• Subjects: 3T3-L1; Adipocytes; Adipogenesis; Adipose tissue (brown); Adipose tissues; Alfacalcidol; Animals; BAT; Biochemistry; Body fat; Bone turnover; Brown adipocyte; C3H10T1/2; Calcifediol; Calcitriol; Cardiovascular disease; Cell Biology; Cell differentiation; Cell proliferation; Cytotoxicity; Fibroblasts; Gene expression; Genetic transcription; Glucose metabolism; Homeostasis; Insulin; Laboratories; Lipid metabolism; Lipids; Metabolic disorders; Metabolic syndrome; Metabolites; Mice; Molecular Biology; Obesity; Peroxisome proliferator-activated receptors; Physiological aspects; Physiology; Proteins; Reverse transcription; Risk factors; Scientific equipment and supplies industry; Thermogenesis; Tomography; Uncoupling protein 1; Vitamin D; Vitamin D3; Vitamin deficiency; Vitamins - pharmacology; Western blotting
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.14785

Brown adipose tissue (BAT) dissipates caloric energy as heat and plays a role in glucose and lipid metabolism. Therefore, augmentation and activation of BAT are the focus of new treatment strategies against obesity, a primary risk factor of metabolic syndrome. The vitamin D system plays a crucial role in mineral homeostasis, bone metabolism, and cell proliferation and differentiation. In this study, we investigated the effects of vitamin D [1,25(OH) D ] on brown adipocyte differentiation. The mouse fibroblast-like cell line C3H10T1/2 was differentiated into brown adipocytes in the presence of 1,25(OH) D . The effect of 1,25(OH) D on brown adipocyte differentiation was assessed by measuring lipid accumulation, the expression of related genes, and cytotoxicity. The viability of C3H10T1/2 cells was measured using the Cell Counting Kit-8 assay. Gene expression was investigated using quantitative reverse transcription-polymerase chain reaction. Protein expression was estimated using western blotting. 1,25(OH) D inhibited adipocyte differentiation and exerted a cytotoxic effect at 1 nM. However, in the physiological concentration range (50-250 pM), 1,25(OH) D promoted uncoupling protein 1 (UCP1) expression in C3H10T1/2 cells. This effect was not observed when 1,25(OH) D was added 48 h after the initiation of differentiation, suggesting that the vitamin D system acts in the early phase of the differentiation program. We showed that 1,25(OH) D increased the expression of two key regulators of brown adipogenesis, PR domain containing 16 ( ) and peroxisome proliferator-activated receptor coactivator-1 ( ). Furthermore, 1,25(OH) D increased expression in 3T3-L1 beige adipogenesis in a dose-dependent manner. These data indicate the potential of vitamin D and its analogs as therapeutics for the treatment of obesity and related metabolic diseases.