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

High-fructose, high-fat diet consumption (HFHF) is one of the primary causes of non-alcoholic fatt liver disease (NAFLD), which is due to impaired beta-oxidation or apolipoprotein secretion by hepatocytes. Activation of autophagy in hepatocytes could be a therapeutic method against hepatic complicat...

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Published in:Folia histochemica et cytobiologica 2023-01, Vol.61 (4), p.205-216
Main Authors: Hosny, Sara Adel, Moustafa, Mohammed Hafez Ahmed, Mehina, Fatma Mahmoud, Sabry, Marwa Mohamed
Format: Article
Language:English
Subjects:
Animal models
Animals
Apolipoproteins
Autophagy
Diet
Disease Models, Animal
Electron microscopy
Fasting
Fatty liver
Hepatocytes
High fat diet
Immunoreactivity
Intermittent Fasting
Liver
Liver diseases
Male
Non-alcoholic Fatty Liver Disease - drug therapy
Oxidation
Phagosomes
Rapamycin
Rats
Recovery
Sirolimus - pharmacology
Sirolimus - therapeutic use
Structure-function relationships
Subgroups
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Summary:High-fructose, high-fat diet consumption (HFHF) is one of the primary causes of non-alcoholic fatt liver disease (NAFLD), which is due to impaired beta-oxidation or apolipoprotein secretion by hepatocytes. Activation of autophagy in hepatocytes could be a therapeutic method against hepatic complications. This study was designed to compare effects of rapamycin and intermittent fasting-inducing autophagy in rats with experimentally induced nonalcoholic fatty liver. 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. 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. It could be concluded that rapamycin and intermittent fasting significantly improved NAFLD-induced changes of liver structure and function by inducing autophagy in hepatocytes.
ISSN:0239-8508
1897-5631
DOI:10.5603/fhc.95905