Author : Samira Mostafa
CoAuthors : Enas A Abd El-Haleim, Ashraf K Bahgat, Samira Saleh
Source : World J Gastroenterol 2016 March 14; 22(10): 2931-2948
Date of Publication : 10/2017
Abstract :
Abstract
AIM: To evaluate the effect of resveratrol, alone and
in combination with fenofibrate, on fructose-induced
metabolic genes abnormalities in rats.
METHODS: Giving a fructose-enriched diet (FED) to rats for 12 wk was used as a model for inducing hepatic dyslipidemia and insulin resistance. Adult male albino rats (150-200 g) were divided into a control
group and a FED group which was subdivided into
4 groups, a control FED, fenofibrate (FENO) (100
mg/kg), resveratrol (RES) (70 mg/kg) and combined treatment (FENO + RES) (half the doses). All treatments were given orally from the 9th week till the
end of experimental period. Body weight, oral glucose tolerance test (OGTT), liver index, glucose, insulin, insulin resistance (HOMA), serum and liver triglycerides (TGs), oxidative stress (liver MDA, GSH and SOD),serum AST, ALT, AST/ALT ratio and tumor necrosis
factor-α (TNF-α) were measured. Additionally, hepatic gene expression of suppressor of cytokine signaling-3
(SOCS-3), sterol regulatory element binding protein-
1c (SREBP-1c), fatty acid synthase (FAS), malonyl CoA
decarboxylase (MCD), transforming growth factor-β1 (TGF-β1) and adipose tissue genes expression of leptin
and adiponectin were investigated. Liver sections were taken for histopathological examination and steatosis area were determined.
RESULTS: Rats fed FED showed damaged liver,
impairment of glucose tolerance, insulin resistance, oxidative stress and dyslipidemia. As for gene expression, there was a change in favor of dyslipidemia
and nonalcoholic steatohepatitis (NASH) development. All treatment regimens showed some benefit in
reversing the described deviations. Fructose caused deterioration in hepatic gene expression of SOCS-3, SREBP-1c, FAS, MDA and TGF-β1 and in adipose tissue
gene expression of leptin and adiponectin. Fructose showed also an increase in body weight, insulin
resistance (OGTT, HOMA), serum and liver TGs, hepatic MDA, serum AST, AST/ALT ratio and TNF-α compared to control. All treatments improved SOCS-3, FAS, MCD, TGF-β1 and leptin genes expression while only RES and FENO + RES groups showed an improvement in
SREBP-1c expression. Adiponectin gene expression was improved only by RES. A decrease in body weight,HOMA, liver TGs, AST/ALT ratio and TNF-α were
observed in all treatment groups. Liver index was increased in FENO and FENO + RES groups. Serum TGs
was improved only by FENO treatment. Liver MDA was improved by RES and FENO + RES treatments. FENO +
RES group showed an increase in liver GSH content.
CONCLUSION: When resveratrol was given with half the dose of fenofibrate it improved NASH-related fructose-induced disturbances in gene expression
similar to a full dose of fenofibrate.
Key words: Fructose; Nonalcoholic steatohepatitis;
Suppressor of cytokine signaling-3; Sterol regulatory
element binding protein-1c; Fatty acid synthase;
Malonyl CoA decarboxylase; Leptin; Adiponectin;
Transforming growth factor-β; Tumor necrosis factor-α
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