Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 18, 2016; 8(20): 838-843
Published online Jul 18, 2016. doi: 10.4254/wjh.v8.i20.838
Lipogenesis in Huh7 cells is promoted by increasing the fructose: Glucose molar ratio
Fernando Windemuller, Jiliu Xu, Simon S Rabinowitz, M Mahmood Hussain, Steven M Schwarz
Fernando Windemuller, Jiliu Xu, Simon S Rabinowitz, Steven M Schwarz, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
M Mahmood Hussain, Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
Author contributions: Windemuller F performed all the experiments and prepared the initial manuscript draft; Xu J and Rabinowitz SS assisted in study design and interpretation of data, as well as review of the final document; all experiments were performed in the laboratory of Hussain MM, under his guidance; Schwarz SM provided the initial study design, conducted all statistical analyses and wrote the final version of the manuscript.
Institutional review board statement: N/A.
Informed consent statement: N/A.
Conflict-of-interest statement: The authors have no personal, professional or financial relationships relevant to this report.
Data sharing statement: All technical and statistical documents, as well as all data sets, are available from the corresponding author at No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Steven M Schwarz, MD, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, State University of New York Downstate Medical Center, 445 Lenox Rd, Box 49, Brooklyn, NY 11203, United States.
Telephone: +1-718-2708968 Fax: +1-718-2701985
Received: February 20, 2016
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.

Keywords: Hepatocytes, Cholesterol, Triglycerides, Fructose, Glucose

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.