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• W4381376674 abstract "Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and altered hepatic energy metabolism, with imbalanced glucose and lipid metabolism. Nicotinamide riboside (NR) has recently emerged as a potential therapeutic for a broad range of metabolic abnormalities. Here, we evaluate the effect of NR treatment on hepatic substrate metabolism in mice with NAFLD. NAFLD was induced by feeding the animals with a choline-deficient, amino acid-define (CDAA) diet for 4 weeks. Mice (C57BL/6) in the NR treatment group (CDAA+NR) were then put on a NR-containing CDAA diet for 10 weeks while the non-treated animals remained on CDAA. Both groups of animals had similar food consumption and weight gain rates, with comparable liver-to-body weight ratios. At the conclusion of the treatment, isolated livers were perfused via the portal vein with 13C metabolic tracers, i.e. 5.5 mM [1,6-13C]glucose + 0.4 mM [U-13C]long chain fatty acids (LCFA) suspended in bovine serum albumin. Fractional substrate oxidations and flux analyses were done using 13C nuclear magnetic resonance (NMR) spectroscopy. An increasing trend of oxygen consumption rates was observed as a result of NR treatment (1.50±0.43 µmol/min/liver) compared to the CDAA-treated group (0.68±0.15 µmol/min/liver). However, the increase is not statistically different. 13C NMR isotopomer flux analyses revealed that pyruvate dehydrogenase flux relative to citrate synthase flux are comparable across the 2 groups (CDAA: 30±4%; CDAA+NR: 33±10%). No changes in fractional oxidation of 13C-long-chain fatty acids and 13C-glucose were observed as a result of nicotinamide riboside treatment, with 44±2% and 48±3% of Ac-CoA derived from 13C-LCFA in CDAA and CDAA+NR livers, respectively. 13C-glucose contributed as a minor source of Ac-CoA (~4-5%) in both groups. These findings suggest that nicotinamide riboside treatment did not affect substrate, fats vs glucose, utilization in CDAA-induced NAFLD mouse livers. Disclosure Q. Shen: None. J.K. Pugmire: None. U. Suwannasual: None. N.R. Maptue: None. C. Khemtong: None. Funding University of Florida" @default.
• W4381376674 created "2023-06-21" @default.
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• W4381376674 date "2023-06-20" @default.
• W4381376674 modified "2023-09-26" @default.
• W4381376674 title "1592-P: Evaluating Metabolic Effects of Nicotinamide Riboside on Hepatic Substrate Metabolism in CDAA-Induced NAFLD Mice" @default.
• W4381376674 doi "https://doi.org/10.2337/db23-1592-p" @default.
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