Published online Jul 18, 2016. doi: 10.4254/wjh.v8.i20.838
Peer-review started: February 22, 2016
First decision: March 25, 2016
Revised: March 28, 2016
Accepted: June 14, 2016
Article in press: June 16, 2016
Published online: July 18, 2016
AIM: To determine whether hepatocyte lipogenesis, in an in vitro cell culture model, is modulated by adjusting culture media monosaccharide content and concentration.
METHODS: Hepatocytes (Huh7), demonstrating glucose and fructose uptake and lipid biosynthesis, were incubated in culture media containing either glucose alone (0.65-0.72 mmol/L) or isosmolar monosaccharide (0.72 mmol/L) comprising fructose:glucose (F:G) molar ratios ranging from 0.58-0.67. Following a 24-h incubation, cells were harvested and analyzed for total protein, triglyceride (TG) and cholesterol (C) content. Significant differences (P < 0.05) among groups were determined using analysis of variance followed by Dunnett’s test for multiple comparisons.
RESULTS: After a 24 h incubation period, Huh7 cell mass and viability among all experimental groups were not different. Hepatocytes cultured with increasing concentrations of glucose alone did not demonstrate a significant change either in C or in TG content. However, when the culture media contained increasing F:G molar ratios, at a constant total monosaccharide concentration, synthesis both of C and of TG increased significantly [F:G ratio = 0.58, C/protein (μg/μg) = 0.13; F:G = 0.67, C/protein = 0.18, P < 0.01; F:G ratio = 0.58, TG/protein (μg/μg) = 0.06; F:G ratio = 0.67, TG/protein = 0.11, P < 0.01].
CONCLUSION: In an in vitro hepatocyte model, glucose or fructose plus glucose support total cell mass and lipogenic activity. Increasing the fructose:glucose molar ratio (but not glucose alone) enhances triglyceride and cholesterol synthesis. These investigations demonstrate fructose promotes hepatocellular lipogenesis, and they provide evidence supporting future, in vivo studies of fructose’s role in the development of hepatic steatosis and non-alcoholic fatty liver disease.
Core tip: Employing an in vitro hepatocyte culture model, these data demonstrate fructose promotes intracellular synthesis both of cholesterol and of triglyceride. The results support the requirement for future, in vivo investigations to determine whether diets high in fructose are risk factors for hepatic steatosis and development of non-alcoholic fatty liver disease.