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Role of exercise and rapamycin on the expression of energy metabolism genes in liver tissues of rats fed a high?fat diet.

ABSTRACT: The mTOR pathway serves an important role in the development of insulin resistance induced by obesity. Exercise improves obesity?associated insulin resistance and hepatic energy metabolism; however, the precise mechanism of this process remains unknown. Therefore, the present study investigated the role of rapamycin, an inhibitor of mTOR, on exercise?induced expression of hepatic energy metabolism genes in rats fed a high?fat diet (HFD). A total of 30 male rats were divided into the following groups: Normal group (n=6) fed chow diets and HFD group (n=24) fed an HFD for 6 weeks. The HFD rats performed exercise adaptation for 1 week and were randomly divided into the four following groups (each containing six rats): i) Group of HFD rats with sedentary (H group); ii) group of HFD rats with exercise (HE group); iii) group of HFD rats with rapamycin (HR group); and iv) group of HFD rats with exercise and rapamycin (HER group). Both HE and HER rats were placed on incremental treadmill training for 4 weeks (from week 8?11). Both HR and HER rats were injected with rapamycin intraperitoneally at the dose of 2 mg/kg once a day for 2 weeks (from week 10?11). All rats were sacrificed following a 12?16 h fasting period at the end of week 11. The levels of mitochondrial and oxidative enzyme activities, as well as of the expression of genes involved in energy metabolism were assessed in liver tissues. Biochemical assays and oil red staining were used to assess the content of hepatic triglycerides (TGs). The results indicated that exercise, but not rapamycin, reduced TG content in the liver of HFD rats. Further analysis indicated that rapamycin reduced the activity of cytochrome c oxidase, but not the activities of succinate dehydrogenase and ??hydroxyacyl?CoA dehydrogenase in the liver of HFD rats. Exercise significantly upregulated the mRNA expression of peroxisome proliferator?activated receptor ? coactivator 1 ?, while rapamycin exhibited no effect on the mRNA expression levels of hepatic transcription factors associated with energy metabolism enzymes in the liver of HFD rats. Collectively, the results indicated that exercise reduced TG content and upregulated mitochondrial metabolic gene expression in the liver of HFD rats. Moreover, this mechanism may not involve the mTOR pathway.

SUBMITTER: Tu G

PROVIDER: S-EPMC7453655 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Role of exercise and rapamycin on the expression of energy metabolism genes in liver tissues of rats fed a high‑fat diet.

Tu Genghong G Dai Chunyan C Qu Haofei H Wang Yunzhen Y Liao Bagen B

Molecular medicine reports 20200728 4

The mTOR pathway serves an important role in the development of insulin resistance induced by obesity. Exercise improves obesity‑associated insulin resistance and hepatic energy metabolism; however, the precise mechanism of this process remains unknown. Therefore, the present study investigated the role of rapamycin, an inhibitor of mTOR, on exercise‑induced expression of hepatic energy metabolism genes in rats fed a high‑fat diet (HFD). A total of 30 male rats were divided into the following gr ...[more]

PMID: 32945385

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Project description:BACKGOUND:Obesity and dyslipidemia are major risk factors associated with non-alcoholic fatty liver disease (NAFLD). NAFLD refers to the accumulation of fat in more than 5% of the liver without alcohol consumption. NAFLD is the most common liver disease and is rapidly becoming a global public health problem. Maoberry (Antidesma bunius) is a fruit rich in antioxidants, especially phenolic compounds, which are reported to have benefits for patients with NAFLD. METHODS:We evaluated the effect of Maoberry extract on fat metabolism in liver tissues of high fat diet-induced rats. Five (5) groups (n?=?12) of male Sprague-Dawley (SD) rats were divided into those given a high fat diet with no treatment (HF), different dosages of Maoberry extracts (0.38 [ML], 0.76 [MM) and 1.52 [MH] g/kg body weight) and 10?mg/kg statin (STAT). The rats were fed a high fat diet for 4?weeks to induce obesity and subsequently continued more for 12?weeks with treatments of Maoberry extracts or STAT. The levels of triglyceride, liver enzymes, oxidative stress and inflammation markers, triglyceride synthesis regulators, and pathology of the liver in high fat diet-induced rats were investigated. RESULTS:Feeding Maoberry extract in MH groups resulted in decreasing levels of serum alanine aminotransferase (ALT), liver triglyceride, liver thiobarbituric acid reactive substances (TBARS) and mRNA expression of tumour necrosis factor (TNF)-?, interleukin (IL)-6, glycerol-3-phosphate acyltransferase (GPAT)-1 and acetyl-coenzyme A carboxylase (ACC) compared with the HF group (P?<?0.05). Moreover, histopathological study of the liver showed reduced fat droplets in the Maoberry extract treatment groups, especially in MH groups and STAT treatment groups. CONCLUSIONS:The improvements of fat metabolism in liver tissues of rats fed a high-fat diet were observed in Maoberry extracts treatment groups. The underline mechanism that link to fat metabolism might be through the process accompanied with down-regulated the gene expression of key enzymes of lipid production, antioxidant activity, and anti-inflammation properties of Maoberry extracts which contains high levels of phenolic and flavonoid compounds.

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Role of exercise and rapamycin on the expression of energy metabolism genes in liver tissues of rats fed a high?fat diet.

Publications

Role of exercise and rapamycin on the expression of energy metabolism genes in liver tissues of rats fed a high‑fat diet.

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