The differential effects of high-fat and high fructose diets on the liver of male albino rat and the proposed underlying mechanisms.

BACKGROUND: The western-style diet is characterized by the high intake of energy-dense foods. Consumption of either high fructose diet or saturated fat resulted in the development of metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Many researchers studied the effect of high-fat diet (HFD), high fructose diet (HFruD) and high fructose high-fat diet (HFHF) on the liver. The missing data are the comparison effect of these groups i.e. are effects of the HFHF diet on the liver more pronounced? So, this study was designed to compare the metabolic and histopathological effect of the HFD, HFruD, and HFHF on the liver. The proposed underlying mechanisms involved in these changes were also studied.

MATERIALS AND METHODS: 24 rats were divided into four groups: control, HFD, HFruD, and HFHF. Food was offered for 6 weeks. Biochemical, light microscopic, immunohistochemical { Inducible nitric oxide synthase (iNOS) and alpha-smooth muscle actin (α-SMA)}, Real-time PCR (gene expression of TNF-α, IL-6, Bax, BCL2, and caspase 3), histomorphometric analysis and oxidative/antioxidative markers {thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA)/glutathione (GSH) and superoxide dismutase (SOD)} were done.

RESULTS: The HFD, HFruD and HFHF groups developed a cluster of liver disorders; steatosis, necrosis, inflammation, apoptosis, ballooning degeneration and cytoplasmic vacuolations. Internal metabolic impairments include elevated the serum levels of glucose, triglycerides, LDL and decreased the serum levels of HDL and albumin. The immunoreaction of the α-SMA and iNOS was strong in these groups. The oxidant markers (MDA and TBARS) were elevated, while the antioxidant markers (SOD and GSH) were decreased. The area % of collagen, inflammatory markers, caspase 3 and Bax elevated, while the BCL-2/Bax ratio decreased. The decrease of PAS, antioxidant markers and the elevation of the α-SMA, iNOS, inflammatory and oxidant markers were obvious in the HFHF when compared to that of the other groups.

CONCLUSIONS: HFD, HFruD, and HFHF developed morphologic hepatic changes ranging from steatosis to necrosis and inflammation, besides the development of internal metabolic impairments. The chief factors of hepatic injury were fat accumulation in the hepatocytes, oxidative stress and highly elevated iNOS. Compared to the other groups, HFHF's effect was more prominent.