Hepatic retinaldehyde dehydrogenases are modulated by tocopherol supplementation in mice with hepatic steatosis

Abstract

Objectives: 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 alpha- and gamma-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. Methods: Male C57BL/6J mice were divided into four groups: a control diet (CD) group (10% fat, 20% protein, 70% carbohydrates); a CD + TF group (alpha-tocopherol: 0.7 mg.kg.d(-1), gamma-tocopherol: 3.5 mg.kg.d(-1)); a high-fat diet (HFD) group (60% fat, 20% protein, 20% carbohydrates); and a HFD + TF group (0.01 mL.g body weight.d(-1)), 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. Results: 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. Conclusions: The present study demonstrated that alpha- and gamma-TF (1:5 ratio) might play a role in modulating retinol metabolism in the prevention of NAFLD induced by a HFD. (c) 2021 Elsevier Inc. All rights reserved.