Introduction: Globally, non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. It occurs in 20-40% of the population and 70-95% of diabetic and obese patients. NAFLD could progress from steatosis to non-alcoholic steatohepatitis (NASH). Worldwide, fast-food diet (FFD) is widely used due to its convenience and palatability.
Aim of Work: This study aimed at evaluating the hepatic biochemical, histological, and morphometric changes occurred on persistent FFD and sedentary lifestyle in adult male mice, the possibility of premalignant dysplastic changes and the recovery potentiality after FFD discontinuation. Moreover, the possible roles of endoplasmic reticulum (ER) stress and cytochrome-P450-family2-subfamilyE-gene1 (CYP2E1) were assessed.
Materials and Methods: 48 adult male mice were kept singly in cages and grouped into control, FFD and recovery groups. Each group was furtherly divided according to the time of sacrifice. 3 control subgroups with FFD subgroups were sacrificed at 4, 6&8 months. However, the remaining 3 control subgroups with the recovery subgroups were sacrificed at 6, 8&10 months. Biochemical, histological, and morphometric studies were done.
Results: FFD group showed progressive hepatic lesion from accumulation of fat microvesicles to deposition of macrovesicles with ER stress, unfolded protein response (UPR) activation, CYP2E1 over-expression, inflammation & apoptosis. Then, there was development of multiple small dysplastic foci inside the lesion area. The improvement in the recovery group was significant in case of steatosis, non-significant in case of NASH and undetectable in dysplasia.
Conclusion: Chronic FFD with sedentary lifestyle could lead to hepatic steatosis and sequentially to NASH through ER stress, UPR activation and CYP2E1 over-activation. With persistence of FFD and inactive behavior, the insult might progress to dysplasia, a precancerous lesion. Although more time is needed for appropriate assessment of recovery, it could be assumed that hepatic steatosis is easily recoverable, NASH is poorly recoverable while dysplasia is irrecoverable.