title: Vitamin d deficiency attenuates high-fat diet-induced hyperinsulinemia and hepatic lipid accumulation in male mice.
abstract: It is increasingly recognized that vitamin D deficiency is associated with increased risks of metabolic disorders among overweight children. A recent study showed that vitamin D deficiency exacerbated inflammation in nonalcoholic fatty liver disease through activating toll-like receptor 4 in a high-fat diet (HFD) rat model. The present study aimed to further investigate the effects of vitamin D deficiency on HFD-induced insulin resistance and hepatic lipid accumulation. Male ICR mice (35 d old) were randomly assigned into 4 groups as follows. In control diet and vitamin D deficiency diet (VDD) groups, mice were fed with purified diets. In HFD and VDD+HFD groups, mice were fed with HFD. In VDD and VDD+HFD groups, vitamin D in feed was depleted. Feeding mice with vitamin D deficiency diet did not induce obesity, insulin resistance, and hepatic lipid accumulation. By contrary, vitamin D deficiency markedly alleviated HFD-induced overweight, hyperinsulinemia, and hepatic lipid accumulation. Moreover, vitamin D deficiency significantly attenuated HFD-induced up-regulation of hepatic peroxisome proliferator-activated receptor γ, which promoted hepatic lipid uptake and lipid droplet formation, and its target gene cluster of differentiation 36. In addition, vitamin D deficiency up-regulated carnitine palmitoyltrans 2, the key enzyme for fatty acid β-oxidation, and uncoupling protein 3, which separated oxidative phosphorylation from ATP production, in adipose tissue. These data suggest that vitamin D deficiency is not a direct risk factor for obesity, insulin resistance, and hepatic lipid accumulation. Vitamin D deficiency alleviates HFD-induced overweight, hyperinsulinemia, and hepatic lipid accumulation through promoting fatty acid β-oxidation and elevating energy expenditure in adipose tissue.
authors.affiliation: Department of Toxicology (X.-J.L., B.-W.W., C.Z., Y.-H.C., C.-Q.H., H.W., D.-X.X.), Anhui Medical University, Hefei, China, 230032; Anhui Provincial Key Laboratory of Population Health and Aristogenics (X.-J.L., Y.-H.C., H.W., D.-X.X.), Hefei, China, 230032; First Affiliated Hospital (X.-J.L., X.C.), Anhui Medical University, Hefei, China, 230032; and School of Life Science (M.-Z.X.), Anhui Medical University, Hefei, China, 230032.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Liu
authors.forename: Bi-Wei
authors.initials: BW
authors.lastname: Wang
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Mi-Zhen
authors.initials: MZ
authors.lastname: Xia
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.forename: Chun-Qiu
authors.initials: CQ
authors.lastname: Hu
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004435:Eating / Q000187:drug effects; D002149:Energy Intake / Q000187:drug effects; D006946:Hyperinsulinism / Q000209:etiology*; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009765:Obesity / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014808:Vitamin D Deficiency / Q000378:metabolism / Q000503:physiopathology*