Independent of Calorie Intake, Short-term Alternate-day Fasting Alleviates NASH, With Modulation of Markers of Lipogenesis, Autophagy, Apoptosis, and Inflammation in Rats

Abstract

Non-alcoholic steatohepatitis (NASH) is a worldwide health problem. Alternate-day fasting (ADF), although thought to be aggressive, has proven safety and efficacy. We aimed to evaluate the effect of short-term ADF against already established high-fat-fructose (HFF)-induced NASH, independent of the amount of calorie intake, and to study the effect of ADF on lipogenesis, apoptosis, and hepatic inflammation. Male Sprague Dawley rats were divided into two groups: (1) negative control and (2) NASH group fed on HFF for 9 weeks, and then randomized into two subgroups of either HFF alone or with ADF protocol for 3 weeks. The ADF could improve HFF-related elevation in serum lactate dehydrogenase and could decrease the mRNA expression of lipogenesis genes; acetyl CoA carboxylase, peroxisome proliferator-activated receptor γ, and peroxisome proliferator-activated receptor α; apoptotic genes caspase-3, p53, and inflammatory cyclo-oxygenase 2; and immunohistochemical staining for their proteins in liver with upregulation of LC3 and downregulation of P62 immunoexpression. Moreover, ADF ameliorated HFF-induced steatosis, inflammation, ballooning, and fibrosis through hematoxylin and eosin, Oil Red O, and Sirius Red staining, confirmed by morphometric analysis, without significant weight loss. Significant correlation of morphometric parameters with levels of gene expression was found. These findings suggest ADF to be a safe effective therapeutic agent in the management of NASH

Enhanced Autophagic Flux, Suppressed Apoptosis and Reduced Macrophage Infiltration by Dasatinib in Kidneys of Obese Mice

“…Among these TKIs, Dasatinib exhibited prominent autophagy induction in A549 and PC-9 cell lines. Moreover, Elsayed et al [ 47 ] found that the induction of autophagy could attenuate high fat and fructose diet-induced hepatic injury. Furthermore, Sohn et al [ 48 ] stated that stimulation of autophagy by fatty diet rescued the kidney from injury.…”

Suppression of neuronal apoptosis and glial activation with modulation of Nrf2/HO-1 and NF-kB signaling by curcumin in streptozotocin-induced diabetic spinal cord central neuropathy

“…Serum glucose was detected using an Accu check blood glucose meter (Roche Diagnostic, Germany). MDA and GSH were measured following the technique of Elsayed et al (2021a , b) .…”

Autophagy: A Cellular Guardian against Hepatic Lipotoxicity

“…Similarly, low-carb diets have shown beneficial effects in reducing hepatic steatosis in humans [ 126 ]. Interestingly, using preclinical animal models, both calorie restriction and time-restricted feeding have been shown to induce hepatic autophagy [ 63 , 129 , 130 ].…”