title: High fat diet-Induced obesity alters vitamin D metabolizing enzyme expression in mice.
abstract: Low serum 25(OH)D concentrations have been reported in obese humans. Inadequate sun exposure and impaired hepatic 25-hydroxylation have been suggested as possible reasons for obesity-associated vitamin D deficiency; however, the underlying mechanism has not been elucidated. We investigated the effects of high fat diet-induced obesity on vitamin D status and vitamin D metabolizing enzyme expression. Male C57BL mice (4 weeks old) were fed control diet containing 10% energy from fat (control group) or high fat diet containing 45% energy from fat (obese group) for 18 weeks. There were no differences in serum 25(OH)D concentrations between two groups, while serum 1,25(OH)2 D concentrations were significantly higher in obese mice. Hepatic mRNA levels of 25-hydroxylases (Cyp2r1, Cyp27a1, and Cyp2j3) were lower in the obese group (31, 30, and 48% lower, respectively). Renal 1α-hydroxylase (Cyp27b1) mRNA levels were higher and 24-hydroxylase (Cyp24) mRNA levels were lower in the obese group. Serum 1,25(OH)2 D concentrations correlated positively with renal Cyp27b1 expression levels and negatively with renal Cyp24 expression levels. Serum PTH concentrations were higher in obese mice. In visceral adipose tissue, Cyp27a1, Cyp2j3, and vitamin D receptor mRNA levels were higher in obese mice. Overall, vitamin D metabolizing enzyme expression was influenced by high fat diet-induced obesity, which might partly explain the mechanisms of the altered vitamin D endocrine system associated with obesity. Higher serum PTH and 1,25(OH)2 D concentrations in obese mice suggest abnormal regulation of serum 1,25(OH)2 D concentrations due to hyperparathyroidism, which might have contributed to lower hepatic 25-hydroxylase mRNA levels.
authors.affiliation: Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Korea.
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Park
authors.affiliation: Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Korea.
authors.forename: Chan Yoon
authors.initials: CY
authors.lastname: Park
authors.affiliation: Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Korea.|Research Institute of Human Ecology, College of Human Ecology, Seoul National University, Seoul, Korea.
authors.forename: Sung Nim
authors.initials: SN
authors.lastname: Han
mesh_terms: D000818:Animals; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat; D005786:Gene Expression Regulation; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014807:Vitamin D / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D010281:Parathyroid Hormone; D012333:RNA, Messenger; D014807:Vitamin D; D003577:Cytochrome P-450 Enzyme System; C106098:Cyp2j3 protein, rat; C569548:Cyp2r1 protein, mouse; D053493:Cholestanetriol 26-Monooxygenase; C506832:Cyp27a1 protein, mouse; D065668:Vitamin D3 24-Hydroxylase
keywords: 1,25-dihydroxyvitamin D; 25-hydroxyvitamin D; hepatic 25-hydroxylase; high fat diet-induced obesity; renal 1α-hydroxylase; renal 24-hydroxylase