Diet high in fructose promotes liver steatosis and hepatocyte apoptosis in C57BL/6J female mice: Role of disturbed lipid homeostasis and increased oxidative stress.

Abstract

The effects of high (H)-fructose (FR) diet (D) (HFRD) on hepatic lipid homeostasis, oxidative stress, inflammation and hepatocyte apoptosis were investigated in 6-week old female C57BL/6J mice fed a regular chow (ContD) or HFRD (35% fructose-derived calories) for 3 weeks. HFRD-fed mice exhibited increased levels of hepatic steatosis with a significant elevation of serum levels of triglyceride, cholesterol and TNFα compared to ContD-fed mice (P<0.05). HFRD-fed mice exhibited ∼2.7- fold higher levels FAS along with significantly decreased protein levels of adiponection-R2 (∼30%), P-AMPK (∼60%), P-ACC (∼70%) and RXR-α (∼55%), suggesting decreased hepatic fat oxidation compared to controls. Interestingly, hepatic fatty acid uptake into hepatocytes and lipolysis were significantly increased in HFRD-fed mice, as shown by decreased CD36 and fatty acid transporter protein-2, and increased adipose triglyceride lipase, respectively (P<0.05). Increased hepatic levels of iNOS and GSSG/GSH suggest elevated oxidative stress with a higher number of macrophages in the adipose tissue in HFRD-fed mice (P<0.05). Significantly elevated rates of hepatocyte apoptosis (∼2.4-fold), as determined by TUNEL analysis with increased Bax/Bcl2 ratio and PARP-1 levels (∼2- and 1.5-fold, respectively), were observed in HFRD-fed mice. Thus, HFRD exposure increased hepatic steatosis accompanied by oxidative stress and inflammation, leading to hepatocyte apoptosis.

• Authors: Youngshim Choi, Mohamed A Abdelmegeed, Byoung-Joon Song
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 103 Pg. 111-121 (May 2017) ISSN: 1873-6351 [Electronic] England
• PMID: 28257781 (Publication Type: Journal Article)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Fas protein, mouse
• Triglycerides
• fas Receptor
• Fructose
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Scd1 protein, mouse
• Stearoyl-CoA Desaturase
• Glutathione

Topics

• Animals
• Apoptosis (drug effects)
• Body Weight (drug effects)
• Female
• Fructose (adverse effects)
• Glutathione (metabolism)
• Hepatocytes (drug effects, metabolism, pathology)
• Lipid Metabolism (drug effects)
• Mice, Inbred C57BL
• Nitric Oxide Synthase Type II (metabolism)
• Non-alcoholic Fatty Liver Disease (chemically induced, pathology)
• Oxidative Stress (drug effects)
• Panniculitis (chemically induced, metabolism)
• Stearoyl-CoA Desaturase (metabolism)
• Triglycerides (blood, metabolism)
• fas Receptor (metabolism)