Lycopene and its metabolite apo‐10’‐lycopenoic acid suppressed high‐fat diet‐induced hepatic steatosis in beta‐carotene‐9’,10’‐oxygenase knockout mice (39.3)

Abstract

Prevalence of non‐alcoholic fatty liver disease is associated with the current obesity epidemic. Lycopene (LYC), which can generate apo‐10’‐lycopenoic acid (APO10LA) endogenously by beta‐carotene‐9’,10’‐oxygenase (BCO2), has been shown to modulate adipose and hepatic lipid metabolism. We examined whether BCO2 is essential for LYC’s biological effects. 12‐week supplementation of either LYC (100 mg/kg diet) or APO10LA (10 mg/kg diet) inhibited high‐fat diet (HFD)‐induced hepatic steatosis (by 77% vs 63% respectively) in BCO2‐knockout (BCO2‐KO) mice. APO10LA‐mediated steatosis suppression was associated with up‐regulated hepatic sirtuin 1 protein expression, and reduced de novo lipogenic markers (Scd1 gene; AMPK, ACC phosphorylation). These APO10LA‐mediated effects were absent in the LYC group. Intriguingly, LYC induced gene expression involved in fatty acid (FA) uptake (Lpl, Fatp4), FA β‐oxidation (Pparα, Lcad), and mitochondrial uncoupling (Ucp3) in mesenteric adipose tissue (MAT), and these LYC‐mediated effects were not present in APO10LA‐fed mice. Importantly, MAT Lpl and Ucp3 expressions were negatively correlated with hepatic steatosis, suggesting that LYC may reduce FA delivery from MAT to the liver. Taken together, this data provided novel insights that LYC and APO10LA may inhibit HFD‐induced steatosis in BCO2‐KO mice through differential mechanisms.Grant Funding Source: USDA/ARS grant 1950‐51000‐074S