Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5560226 | Food and Chemical Toxicology | 2017 | 11 Pages |
â¢HFRD-fed mice exhibited higher levels of hepatic lipogenesis as evidenced by increased FAS and SCD1.â¢Hepatic fatty acid oxidation was inhibited as evidenced by decreased adiponection-R2, P-AMPK, P-ACC, and RXR-α.â¢HFRD increased the hepatic levels of iNOS and GSSG/GSH, suggesting the development of oxidative stress.â¢HFRD-fed mice elevated the levels of macrophages and pro-inflammatory cytokine TNF-α in the adipose tissue.â¢HFRD-fed mice exhibited increased hepatocyte apoptosis, as shown by the elevated levels of Bax/Bcl2 ratio and PARP-1 protein.
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 â¼2.7- fold higher levels FAS along with significantly decreased protein levels of adiponection-R2 (â¼30%), P-AMPK (â¼60%), P-ACC (â¼70%) and RXR-α (â¼55%), 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 (â¼2.4-fold), as determined by TUNEL analysis with increased Bax/Bcl2 ratio and PARP-1 levels (â¼2- 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.
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