• Nutrition · Jun 2023

    Nicotinamide riboside and dietary restriction effects on gut microbiota and liver inflammatory and morphologic markers in cafeteria diet-induced obesity in rats.

    • Larisse Longo, Josimar Macedo de Castro, Melina Belén Keingeski, Pabulo Henrique Rampelotto, Dirson João Stein, Gabriel Tayguara Silveira Guerreiro, Valessa Emanoele Gabriel de Souza, Carlos Thadeu Schmidt Cerski, Carolina Uribe-Cruz, TorresIraci L SILSLaboratory of Pain Pharmacology and Neuromodulation: Preclinical Investigations, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Graduate Program in Medicine, Faculty of Medical Sciences, Univers, and Mário Reis Álvares-da-Silva.
    • Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Experimental Laboratory of Hepatology and Gastroenterology, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
    • Nutrition. 2023 Jun 1; 110: 112019112019.

    ObjectivesNo specific therapy is available for metabolic dysfunction-associated fatty liver disease. We investigated nicotinamide riboside (NR) and dietary restriction (DR) effects in liver lipids, inflammation, histology, intestinal permeability, and gut microbiota in a cafeteria diet (CAFD)-induced obesity model.MethodsAdult male Wistar rats were randomly assigned to standard diet (SD) or CAFD. After 6 wk, they were subdivided into six groups-SD + vehicle (Veh) (distilled water), SD + NR (400 mg/kg), DR + Veh, DR + NR, CAFD + Veh, and CAFD + NR-for 4 wk more until euthanasia.ResultsCAFD increased the hepatic content of lipids, triacylglycerols, and total cholesterol and promoted hepatomegaly, steatosis, steatohepatitis, and liver fibrosis. DR intervention successfully delayed the onset of CAFD-induced liver abnormalities except for steatosis and fibrosis. CAFD suppressed Sirt1 expression in the liver and DR increased Sirt3 expression. CAFD did not affect hepatic inflammatory genes but DR enhanced Il10 expression while decreasing Il1β expression. CAFD reduced Firmicutes and increased Bacteroidetes and Cyanobacteria, with no changes in intestinal permeability. Gut microbiota patterns in animals exposed to DR were similar to those of animals in SD. NR, specifically in CAFD, reduced hepatic triacylglycerols and total cholesterol deposition and collagen fiber accumulation in the liver and limited the colonization of CAFD-induced Cyanobacteria. NR combined with DR decreased the liver's relative weight and Tnfα expression and suppressed Sirt1 and Sirt3 hepatic expression.ConclusionsThis study suggests that NR can be a potential adjuvant to metabolic dysfunction-associated fatty liver disease therapy, encouraging further research in this field.Copyright © 2023. Published by Elsevier Inc.

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