Gordana MATIC, Natasa VELICKOVIC, Ana TEOFILOVIC, Biljana BURSAC, Ana DJORDJEVIC, Danijela VAJNOVIC MILUTINOVIC

High dietary fructose load aggravates lipid metabolism in the liver of Wistar rats through imbalance between lipogenesis and fatty acid oxidation

Fructose ingestion is often associated with hepatic steatosis and hypertriglyceridemia. The homeostasis of hepatic lipids is mainly determined by the interplay of lipogenesis and fatty acid β-oxidation. In this study, we hypothesized that high fructose intake disturbs hepatic lipid metabolism through an imbalance between these processes. Therefore, we analyzed the effects of a 9-week-long consumption of a 60% fructose solution on physiological parameters, glycemia, and blood lipid profiles in male Wistar rats. The expression of key regulators of fatty acid oxidation (FAO) and lipogenesis in the liver were assessed by western blot and quantitative polymerase chain reaction. The results showed that fructose-fed rats were normoglycemic and hypertriglyceridemic with visceral adiposity, but without hepatic lipid deposition. A high-fructose diet is associated with increased nuclear levels of the lipogenic regulator sterol regulatory element binding protein 1c (SREBP-1c), which was followed by increased acetyl-CoA carboxylase and fatty acid synthase mRNAs. The nuclear level of the FAO transcriptional regulators peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1) and lipin-1 were unaltered, while carnitine palmitoyltransferase 1 (CPT1) mRNA was significantly decreased. Overall, our findings showed that liquid fructose overconsumption is associated with perturbation of hepatic lipid metabolism through predominance of lipogenesis over β-oxidation, resulting in spillover of triglycerides and visceral adiposity.

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