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

Abstract

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-weeklong 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.

Protective Role of Picralima nitida Seed Extract in High-Fat High-Fructose-Fed Rats

“…In the liver, glucokinase plays a critical catalytic role by promoting the addition of a phosphate group to glucose, thereby enhancing its uptake in the liver [ 51 , 52 ]. Phosphoenolpyruvate carboxykinase, on the other hand, is a crucial enzyme in the gluconeogenesis pathway that helps to increase glucose production [ 53 ]. Reduced expression of glucokinase in the liver may be a result of the elevated plasma glucose concentration observed in rats fed an HFHF diet only indicating an inability to promote glucose uptake in the liver despite elevated insulin levels.…”

“…Activators of glucokinase have been shown to be important in the treatment of diabetes [ 52 , 54 ]. The mRNA expression level of carnitine palmitoyltransferase 1 α (CPT-1 α ), an important enzyme that aids the transport of long-chain free fatty acids into the mitochondria where they undergo β -oxidation, has been shown to decrease in experimental rodents fed a high-fat diet, high fructose diet, or high-fat high fructose combined diet [ 53 , 55 – 57 ]. Conversely, mRNA expression of HMG-COA reductase, a rate-limiting enzyme of the cholesterol biosynthetic pathway, has been reported to increase following the consumption of a high-fat diet in rats [ 58 , 59 ].…”

Fructose and metabolic health: governed by hepatic glycogen status?

“…), and chronic fructose ingestion in rats leads to an increase in hepatic lipogenic genes as well as a concurrent decrease in hepatic carnitine palmitoyltransferase 1 (CPT1) (Teofilovic et al . ). This suggests that fructose increases net hepatic lipid production from multiple mechanisms, not solely an increase in lipogenesis.…”

“…B, high hepatic glycogen status determines that ingested fructose is shunted away from glycogen synthesis and towards lipogenic pathways, which leads to greater VLDL export. G-6-P, glucose-6-phosphate; G-1-P, glucose-1-phosphate; UDP, uridine diphosphate glucose; F-1-P, fructose-1-phosphate; F-6-P, fructose-6-phosphate; F-1,6-P 2 , carnitine palmitoyltransferase 1 (CPT1) (Teofilovic et al 2016). This suggests that fructose increases net hepatic lipid production from multiple mechanisms, not solely an increase in lipogenesis.…”