Fructose and glucose combined with free fatty acids induce metabolic disorders in HepG2 cell: A new model to study the impacts of high-fructose/sucrose and high-fat diets in vitro.

Abstract

This work investigated the underlying mechanism of high-fructose/sucrose and high-fat diets, which rapidly induce metabolic syndrome in vivo, via a new cell model. Glucose and/or fructose were used to induce the human hepatoma cell (HepG2) in the presence of palmitic acid, oleic acid, or combined fatty acids (CFA) for 24 h. The alterations in lipid and uric acid production, glucose metabolism, oxidative status, and related genes and proteins were monitored. The cell model that featured metabolic disorders was established by treatment of 10 mM glucose and 15 mM fructose plus 1 mM CFA. Results showed that palmitic acid mainly induced insulin resistance, oxidative stress, and triglyceride (TG) secretion, whereas oleic acid mainly contributed to intracellular TG. Fructose was mainly responsible for uric acid and cholesterol production. In addition, fructose synergistically elevated the intra- and extracellular TG and extracellular malonaldehyde with glucose and CFA. Regulations of genes and proteins associated with carbohydrate metabolism and lipogenesis partially explained the action of fructose in inducing the metabolic disorders in cell. The combination of glucose, fructose, and CFA could successfully induce metabolic disorders in HepG2 cells, including dyslipidemia, insulin resistance, hyperuricemia, and oxidative stress.