Dietary Tomato Powder Feeding Attenuated Non-Alcoholic Fatty Liver Disease Independent of Sirtuin1 Activity in Mice

Objectives: Sirtuin 1 (SIRT1) is a highly conserved NAD+-dependent protein deacetylase that modulates lipid metabolism, oxidative stress, and inflammation. We have previously shown that whole tomato (tomato powder, TP) and lycopene inhibited high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) by modulating SIRT1 activity in animal models. Whether dietary TP inhibits NAFLD and HCC dependent on SIRT1 activity remains unknown. Methods: Mice with homozygous ablation in catalytic activity of SIRT1 (MT) and their corresponding wild type littermates (WT) were injected with the carcinogen diethylnitrosamine at two weeks of age. At six weeks of age, mice were fed with a HFD (60% total calories from fat) with or without TP (containing lycopene 100 mg/kg diet or equivalent to dietary lycopene intake of 8.1 mg per day in humans) for 34 weeks. Pathological and biochemical variables were assessed in the liver, mesenteric adipose tissue, and plasma. Results: TP feeding significantly reduced plasma levels of triglycerides, hepatic steatosis score, and inflammatory foci in HFD-fed WT and MT mice at comparable hepatic lycopene concentrations (7.7 ± 1.7 and 7.4 ± 2.0 nmol/g liver, respectively). However, the beneficial effects of TP feeding were achieved through different molecular mechanisms: In WT mice, the protective effect of TP was associated with increased hepatic SIRT1 protein expression and activity, along with decreased mRNA expressions of caspase-1 and fatty acid-binding protein 1. Moreover, TP feeding lowered the concentration of hepatic IL-1β protein; In MT mice, TP feeding decreased hepatic levels of malondialdehyde, acetylated-p53, and acetyl-CoA carboxylase, and increased mRNA expressions of glutathione peroxidase-1 and AMP-kinase phosphorylation. Furthermore, TP feeding significantly lowered the mRNA expression of IL-6 in mesenteric adipose tissue and the protein concentration of IL-6 in both plasma and the liver. Neither the lack of SIRT1 activity nor TP feeding altered the incidence, multiplicity, and volume of HCC in both WT and MT mice. Conclusions: The present study demonstrates that dietary TP, independent of SIRT1 activity, ameliorates HFD-induced NAFLD, oxidative stress, and inflammatory responses in the liver and mesenteric adipose tissue. Funding Sources: Supported by USDA/NIFA/AFRI and USDA/ARS.