Therapeutic effect of autophagy induced by rapamycin versus intermittent fasting in animal model of fatty liver

雷帕霉素诱导自噬与间歇性禁食对脂肪肝动物模型的治疗作用

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作者:Sara Adel Hosny, Mohammed Hafez Ahmed Moustafa, Fatma Mahmoud Mehina, Marwa Mohamed Sabry

Conclusions

It could be concluded that rapamycin and intermittent fasting significantly improved NAFLD-induced changes of liver structure and function by inducing autophagy in hepatocytes.

Material and methods

Male rats were divided into five groups: C (control, n = 6), the experimental group (EX) subdivided, EXIa (HFHF, n = 6), EXIb (recovery, n = 6), EXII (rapamycin, n = 6) and EXIII (intermittent fasting, n = 6). All rats in the experimental group received HFHF diet for 8 weeks to induce nonalcoholic-fatty liver and obesity. Then, for the next 8 weeks the animals received either a daily oral dose of rapamycin (EXII group) or to intermittent fasting (IF) for 16 hours daily (EXIII group). Blood samples were drawn, and serum TG concentration as well as ALT and AST activities were determined. Hepatic sections were examined by light and electron microscopy. LC3B immunohistochemical staining, morphometric and statistical studies were performed.

Methods

Male rats were divided into five groups: C (control, n = 6), the experimental group (EX) subdivided, EXIa (HFHF, n = 6), EXIb (recovery, n = 6), EXII (rapamycin, n = 6) and EXIII (intermittent fasting, n = 6). All rats in the experimental group received HFHF diet for 8 weeks to induce nonalcoholic-fatty liver and obesity. Then, for the next 8 weeks the animals received either a daily oral dose of rapamycin (EXII group) or to intermittent fasting (IF) for 16 hours daily (EXIII group). Blood samples were drawn, and serum TG concentration as well as ALT and AST activities were determined. Hepatic sections were examined by light and electron microscopy. LC3B immunohistochemical staining, morphometric and statistical studies were performed.

Results

Subgroups EXIa (HFHF subgroup) and EXIb (Recovery subgroup) showed marked increase in TG, ALT, and AST levels associated with loss of normal hepatic architecture, cytoplasmic vacuolations and faint LC3B immunoreactivity. Ultrathin sections exhibited many autophagosomes in hepatocytes. On the other hand, rapamycin (EXII) and IF (EXIII) groups showed significant improvement to a variable extent in comparison to EXI groups. Conclusions: It could be concluded that rapamycin and intermittent fasting significantly improved NAFLD-induced changes of liver structure and function by inducing autophagy in hepatocytes.

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