Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua, Chile.
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Nutrition. 2022 Feb;94:111539. doi: 10.1016/j.nut.2021.111539. Epub 2021 Nov 17.
An altered retinol metabolism might play a role in the development of nonalcoholic fatty liver disease (NAFLD). Tocopherols (TF) modulate metabolic pathways and have been proposed as a complementary treatment of obesity-induced metabolic alterations. Moreover, there is evidence suggesting that TF may modulate retinol metabolism. The aim of this study was to evaluate whether the dietary supplementation of α- and γ-TF modulates the expression of hepatic retinaldehyde dehydrogenases, RALDH1, RALDH2, and RALDH3 (involved in retinol metabolism) and, lipogenic factors sterol regulatory element binding protein-1c (SREBP-1c) and cluster differentiation 36 (CD36) in an animal model of diet-induced NAFLD.
Male C57BL/6J mice were divided into four groups: a control diet (CD) group (10% fat, 20% protein, 70% carbohydrates); a CD + TF group (α-tocopherol: 0.7 mg·kg·d, γ-tocopherol: 3.5 mg·kg·d); a high-fat diet (HFD) group (60% fat, 20% protein, 20% carbohydrates); and a HFD + TF group (0.01 mL·g body weight·d), for 12 wk. General parameters (body-adipose tissue weight, glucose-triacylglyceride serum levels), liver steatosis (histology, liver triacylglycerides content), and hepatic RALDH1, RALDH2, RALDH3, SREBP-1c and CD36 (qPCR, quantitative polymerase chain reaction; IHQ, immunohistochemistry) were measured.
TF supplementation in HFD-fed mice decreased the presence of lipid vesicles (90%) and total lipid content (75%) and downregulated the expression of RALDH1, RALDH3, SREBP-1c, and CD36.
The present study demonstrated that α- and γ-TF (1:5 ratio) might play a role in modulating retinol metabolism in the prevention of NAFLD induced by a HFD.
视黄醇代谢的改变可能在非酒精性脂肪性肝病（NAFLD）的发展中起作用。生育酚（TF）调节代谢途径，并被提议作为肥胖引起的代谢改变的补充治疗。此外，有证据表明 TF 可能调节视黄醇代谢。本研究旨在评估膳食补充 α-和 γ-TF 是否调节肝视黄醛脱氢酶（RALDH1、RALDH2 和 RALDH3，参与视黄醇代谢）和脂肪生成因子固醇调节元件结合蛋白-1c（SREBP-1c）和簇分化 36（CD36）的表达在饮食诱导的 NAFLD 动物模型中。
雄性 C57BL/6J 小鼠分为四组：对照组（10%脂肪、20%蛋白质、70%碳水化合物）；对照组+TF 组（α-生育酚：0.7 mg·kg·d，γ-生育酚：3.5 mg·kg·d）；高脂肪饮食组（60%脂肪、20%蛋白质、20%碳水化合物）；高脂肪饮食+TF 组（0.01 mL·g 体重·d），持续 12 周。测量一般参数（体重-脂肪组织重量、血糖-甘油三酯血清水平）、肝脂肪变性（组织学、肝甘油三酯含量）和肝 RALDH1、RALDH2、RALDH3、SREBP-1c 和 CD36（qPCR、定量聚合酶链反应；IHQ、免疫组织化学）。
TF 补充剂可减少 HFD 喂养小鼠的脂质泡存在（90%）和总脂质含量（75%），并下调 RALDH1、RALDH3、SREBP-1c 和 CD36 的表达。
本研究表明，α-和 γ-TF（1:5 比例）可能在调节视黄醇代谢中起作用，从而预防 HFD 引起的 NAFLD。
