School of Medicine, Faculty of Health, University of Tasmania, Hobart, Tasmania 7000, Australia.
Nutrients. 2017 Sep 7;9(9):985. doi: 10.3390/nu9090985.
Both dietary fat and vitamin D deficiency have been linked with increased incidence of non-alcoholic fatty liver disease and insulin resistance. While sex differences in disease prevalence and severity are well known, the impact on disease pathogenesis remains unclear. To further explore the effect of these exposures on metabolic function, C57BL/6 male and female mice were weaned onto one of four diets; low fat vitamin D replete, low fat vitamin D deficient, or two high fat diets, one vitamin D replete and one deficient. Visceral fat, hepatic adiposity, and insulin resistance were measured after five and a half weeks. Vitamin D deficiency, independent of dietary fat, increased hepatic fat accumulation in both sexes ( = 0.003), although did not increase hepatic expression of interleukin-6 ( = 0.92) or tumor necrosis factor-α ( = 0.78). Males were observed to have greater insulin resistance (glucose area under the curve: < 0.001, homeostatic model assessment for insulin resistance: = 0.046), and have greater visceral adiposity ( < 0.001), while female mice had greater hepatic fat accumulation ( < 0.001). This study is the first to demonstrate vitamin D deficiency alone can cause hepatic accumulation while also being the first to observe higher liver fat percentages in female mice.
膳食脂肪和维生素 D 缺乏与非酒精性脂肪肝和胰岛素抵抗的发病率增加有关。尽管疾病的患病率和严重程度存在性别差异已得到广泛认可，但这些差异对疾病发病机制的影响仍不清楚。为了进一步探讨这些暴露因素对代谢功能的影响，将 C57BL/6 雄性和雌性小鼠分别用四种饮食中的一种喂养至断奶：低脂肪维生素 D 充足、低脂肪维生素 D 缺乏、或两种高脂肪饮食，一种维生素 D 充足，另一种缺乏。喂养五周半后测量内脏脂肪、肝脂肪堆积和胰岛素抵抗。无论饮食脂肪如何，维生素 D 缺乏都会增加两性的肝脂肪堆积（ = 0.003），但不会增加白细胞介素-6（ = 0.92）或肿瘤坏死因子-α（ = 0.78）的肝表达。研究发现雄性的胰岛素抵抗更严重（血糖曲线下面积： < 0.001，胰岛素抵抗的稳态模型评估： = 0.046），内脏脂肪更多（ < 0.001），而雌性小鼠的肝脂肪堆积更多（ < 0.001）。本研究首次证明了单独的维生素 D 缺乏会导致肝脏堆积，同时也是首次观察到雌性小鼠的肝脏脂肪百分比更高。
