Lipid Biochemistry Division, National Institute of Nutrition, Jamai Osmania-Post, Hyderabad 500007, India.
Pathology Division, National Institute of Nutrition, Jamai Osmania-Post, Hyderabad 500007, India.
Exp Cell Res. 2018 Mar 1;364(1):104-112. doi: 10.1016/j.yexcr.2018.01.040. Epub 2018 Feb 1.
Previously, we reported that vitamin A deficiency resulted in the reduction of stearoyl-CoA desaturase 1 (SCD1) and monounsaturated fatty acid (MUFA) levels, which corroborated with attenuation of high fructose-induced hepatic steatosis. Here, we aimed at assessing the effect of vitamin A deficiency on SCD1, MUFA levels and their impact on pancreas' structure and functions. Male weanling Wistar rats fed one of the four diets, namely control (Con), vitamin A-deficient (VAD), highfructose (HFr) and vitamin A-deficient diet with highfructose (VADHFr) for 16 weeks period. Compared to the control, feeding of VAD diet (alone or with HFr) resulted in pancreatic intra-islet vessel dilation and reduced plasma insulin, glucagon and C-peptide levels, however, glucose levels decreased only in VADHFr group. In line with plasma levels, VAD diet-fed animals displayed lower immunostaining for insulin and glucagon, which corroborated with increased apoptotic staining observed in the islet regions, possibly due to increased cellular stress, as indicated by high immunostaining for endothelial nitric oxide synthase (eNOS) and CCAAT/Enhancer-binding protein homologues protein (CHOP). On the other hand, it significantly decreased the SCD1 protein, which corroborated with reduced MUFA levels, particularly, oleic acid (C18:1), when compared to the control and HFr groups. In conclusion, chronic vitamin A deficiency altered the structure and functions of pancreas by diminishing the islet cells, possibly by inducing cellular stress-mediated apoptosis and decreasing SCD1-mediated oleic acid (C18:1) synthesis. Thus, the data suggest that unlike liver, the reduction in SCD1 and MUFA levels in the pancreas exerts deleterious effects on its functions and perturb the overall cellular metabolism.
先前，我们曾报道过维生素 A 缺乏会导致硬脂酰辅酶 A 去饱和酶 1（SCD1）和单不饱和脂肪酸（MUFA）水平降低，这与高果糖诱导的肝脂肪变性减轻相一致。在此，我们旨在评估维生素 A 缺乏对 SCD1、MUFA 水平的影响，以及它们对胰腺结构和功能的影响。雄性断奶 Wistar 大鼠喂食四种饮食中的一种，即对照（Con）、维生素 A 缺乏（VAD）、高果糖（HFr）和维生素 A 缺乏加高果糖（VADHFr）饮食，为期 16 周。与对照相比，喂食 VAD 饮食（单独或与 HFr 一起）导致胰岛内血管扩张和血浆胰岛素、胰高血糖素和 C 肽水平降低，但仅在 VADHFr 组中血糖降低。与血浆水平一致，喂食 VAD 饮食的动物显示胰岛素和胰高血糖素免疫染色减少，这与胰岛区域观察到的凋亡染色增加一致，这可能是由于细胞应激增加，内皮型一氧化氮合酶（eNOS）和 CCAAT/增强子结合蛋白同源物蛋白（CHOP）的免疫染色增加表明。另一方面，它显著降低了 SCD1 蛋白，这与 MUFA 水平降低有关，特别是油酸（C18:1），与对照和 HFr 组相比。总之，慢性维生素 A 缺乏通过减少胰岛细胞来改变胰腺的结构和功能，可能通过诱导细胞应激介导的细胞凋亡和减少 SCD1 介导的油酸（C18:1）合成来实现。因此，数据表明，与肝脏不同，胰腺中 SCD1 和 MUFA 水平的降低对其功能产生有害影响，并扰乱整体细胞代谢。
