(OR04-02-25) Feeding Phytoene, an Upstream Plant Precursor of Lycopene in Tomatoes, Attenuated Nonalcoholic Fatty Liver Disease in Mice

Objectives: Previous studies suggest that lycopene alone is not solely responsible for the health benefits of tomato consumption against nonalcoholic fatty liver disease (NAFLD) but may instead be independently related to other bioactive components in tomatoes. Phytoene (PTE), an upstream precursor of major carotenoids abundantly present in tomatoes, has been largely overlooked despite its demonstrated bioavailability in humans and animals. In this study, we investigated whether dietary PTE contributes to the protective effects of tomatoes against high refined carbohydrate diet (HRCD)-induced NAFLD in mice.

Methods: Eight-week-old C57BL/6J male mice were fed a semi-purified HRCD (66.5% carbohydrates, including sucrose) with or without PTE concentrate, extracted from tomatoes, for 24 weeks. The PTE dosage (100 mg/kg diet) was equivalent to the daily consumption of 2-3 medium-sized tomatoes in humans. Liver pathology, biochemical markers, and molecular variables were assessed.

Results: There was no difference in final body weight and liver weight between the groups. PTE feeding significantly reduced HRCD-induced hepatic steatosis scores (P  < 0.00>1) and hepatic triglyceride levels (P  < 0.05) compared to HRCD-fed controls. These protective effects were associated with: 1) increased hepatic mRNA and protein expression of the deacetylase sirtuin 1; 2) increased hepatic AMPK phosphorylation and acetyl-CoA carboxylase (ACC) 1 phosphorylation; and 3) upregulated hepatic mRNA expression of mitochondrial fatty acid oxidation genes, including Cpt1a, Hadha, and Acadm. No significant changes were observed in biomarkers of de novo lipogenesis, including Acly, Fasn, and Scd1. Additionally, we did not detect any hepatic inflammatory foci and changes in the mRNA expression of pro-inflammatory cytokines, such as Il-6 and Il-1β.

Conclusions: Dietary PTE is a biologically active compound that attenuates HRCD-induced NAFLD in mice. Its protective effects may involve the regulation of sirtuin 1 deacetylation and the enhancement of mitochondrial fatty acid oxidation through the AMPK-ACC axis.

Funding Sources: This work was supported by USDA/NIFA/AFRI and USDA/ARS.