of Medical Study in the San Carlos Clinic Hospital (IdISSC), Complutense University of Madrid, Ciudad Universitaria, 28040 Madrid, Spain Division of Biochemistry and Molecular Biology, Faculty of Medicine, Institute of Health-related Study at the San Carlos Clinic Hospital (IdISSC), Complutense University of Madrid, Ciudad Universitaria, 28040 Madrid, Spain; [email protected] (P.D.); [email protected] (A.P.-G.); [email protected] (E.) Division of Cell Biology, Faculty of Medicine, Institute of Health-related Study in the San Carlos Clinic Hospital (IdISSC), Complutense University of Madrid, Ciudad Universitaria, 28040 Madrid, Spain; [email protected] Correspondence: [email protected] These authors have contributed equally to this operate.Citation: Hurtado-Carneiro, V.; Dongil, P.; P ez-Garc , A.; varez, E.; Sanz, C. Preventing Adenosine A1 receptor (A1R) Agonist Purity & Documentation oxidative Strain within the Liver: An Chance for GLP-1 and/or PASK. Antioxidants 2021, ten, 2028. doi.org/ ten.3390/antiox10122028 Academic Editors: Teresa Carbonell Cam and Joan RosellCatafauAbstract: The liver’s higher metabolic activity and detoxification functions generate reactive oxygen species, mainly via oxidative phosphorylation inside the mitochondria of hepatocytes. In contrast, it also has a potent antioxidant mechanism for counterbalancing the oxidant’s impact and relieving oxidative anxiety. PAS kinase (PASK) can be a serine/threonine kinase containing an N-terminal Per-ArntSim (PAS) domain, in a position to detect redox state. Through fasting/feeding modifications, PASK regulates the expression and activation of critical liver proteins involved in carbohydrate and lipid metabolism and mitochondrial biogenesis. Interestingly, the functional inactivation of PASK prevents the improvement of a high-fat diet program (HFD)-induced obesity and diabetes. Furthermore, PASK deficiency alters the activity of other nutrient sensors, which include the AMP-activated protein kinase (AMPK) as well as the mammalian target of rapamycin (mTOR). Furthermore for the expression and subcellular localization of nicotinamide-dependent histone deacetylases (SIRTs). This overview focuses on the connection between oxidative stress, PASK, along with other nutrient sensors, updating the restricted knowledge around the role of PASK within the antioxidant response. We also comment on glucagon-like peptide 1 (GLP-1) and its collaboration with PASK in preventing the damage linked with hepatic oxidative anxiety. The present information would recommend that PASK inhibition and/or exendin-4 therapy, in particular beneath fasting situations, could ameliorate issues linked with excess oxidative stress. Keywords and phrases: exendin-4; metabolic sensors; antioxidantsReceived: 19 October 2021 AT1 Receptor Antagonist Species Accepted: 15 December 2021 Published: 20 DecemberPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.1. Introduction The liver is often a very important organ for adapting to nutritional alterations (e.g., fasting/feeding states) by responding appropriately to achieve metabolic and power homeostasis via its role in the storage and redistribution of carbohydrates, proteins, vitamins, and lipids. two. Liver Metabolic Functions and Detoxification Immediately after food intake, the liver shops glucose as glycogen, facilitating glycemic control [1]. In addition, the excess carbohydrate in carbohydrate-rich diets is converted into fatty acids through de novo lipogenesis [2,3]. By contrast, the liver produces glucose beneath fasting circumstances, 1st by glycogenolysis and subsequently via hepatic