Diet high in fructose promotes liver steatosis and hepatocyte apoptosis in C57BL/6J female mice: Role of disturbed lipid homeostasis and increased oxidative stress. (May 2017)

• Record Type: Journal Article
• Authors: Choi, Youngshim; Abdelmegeed, Mohamed A.; Song, Byoung-Joon
• Is Part Of: Food and chemical toxicology. Volume 103(2017)
• Page Start: 111
• Page End: 121
• Publication Date: 2017-05
• Subjects: ACC acetyl-CoA carboxylase -- Adiponectin R2 adiponectin receptor 2 -- AFLD alcoholic fatty liver disease -- ALT alanine aminotransferase -- AMPK AMP-activated protein kinase -- ATGL adipose triglyceride lipase -- Bax Bcl-2-associated X protein -- Bcl2 B-cell lymphoma 2 -- CAT catalase -- CD36 cluster of differentiation 36 -- ContD regular chow control diet -- FAS fatty acid synthase -- FATP2 fatty acid transport protein 2 -- GSH reduced glutathione -- GSSG oxidized glutathione disulfide -- HFD high fat diet -- HFRD high (H)-fructose (FR) diet (D) -- HO-1 heme oxygenase-1 -- HSL hormone-sensitive lipase -- iNOS inducible nitric oxide synthase -- NAFLD Non-alcoholic fatty liver disease -- P-ACC phospho-acetyl-CoA carboxylase -- P-AMPK phospho-AMP-activated protein kinase -- PARP-1 poly-ADP-ribosyl polymerase-1 -- PPARα peroxisome proliferator-activated receptor α -- RNS reactive nitrogen species -- ROS reactive oxygen species -- RXRα Retinoid X receptor α -- SCD1 stearoyl-CoA desaturase-1 -- SOD superoxide dismutase -- TG triglyceride -- TNFα tumor necrosis factor α -- VLDL very low density lipoprotein; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2017.02.039
• Languages: English
• ISSNs: 0278-6915

Abstract

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. Graphical abstract: Highlights: HFRD-fed mice exhibited higher levels of hepatic lipogenesis as evidenced by increased FAS and SCD1. Hepatic fatty acid oxidation was inhibited as evidenced by decreased adiponection-R2, P-AMPK, P-ACC, and RXR-α. HFRD increased the hepatic levels of iNOS and GSSG/GSH, suggesting the development of oxidative stress. HFRD-fed mice elevated the levels of macrophages and pro-inflammatory cytokine TNF-α in the adipose tissue. HFRD-fed mice exhibited increased hepatocyte apoptosis, as shown by the elevated levels of Bax/Bcl2 ratio and PARP-1 protein.