2) Hepatic Injury
The liver requires FOXOs to maintain cellular and metabolic balance, and FOXO dysregulation may aid in the emergence of Non-alcoholic fatty liver disease (NAFLD) (Dong., 2017). Given the significance of FOXOs in maintaining healthy levels of lipids and glucose, it is not astonishing that abnormalities in hepatic FOXO regulation might contribute to metabolic ailments (Gross et al., 2009). AMP-activated protein kinase (AMPK) plays a crucial function in hepatic metabolic regulation. Once activated, AMPK inhibits energy-consuming biosynthesis processes, such as fatty acid and sterol production, while simultaneously activating ATP-producing catabolic pathways, including fatty acid oxidation  and activates autophagy in the liver (Viollet et al., 2006). FOXO3a phosphorylation has been implicated as a key ROS-activated rapid response. PI3K and the AMPK signalling pathway are the most important sensors of stress signals in the management of FOXO3a-dependent cellular homeostasis. In addition, it has been identified that the AMPK–FOXO3a axis is the key homeostatic signalling framework that regulates the physiological response to oxidative stress (Jin et al., 2022). In addition to Akt/SGK, SIRT1, and PPAR-α, MAPK, an essential metabolic master and cell energy sensor, has been implicated in influencing FOXO3a transcriptional activity. SIRT1 and PPAR-α are reciprocally regulatory. A rise in hepatic SIRT1 enhances PPAR-α activity, and PPAR-α is a crucial factor in the upregulation of SIRT1 gene expression. PPAR-α is a nuclear receptor that stimulates fatty acid oxidation, regulates lipid metabolism, and stimulates autophagy (Gautam et al., 2020).