of Medical Investigation in the San Carlos Clinic Hospital (IdISSC), Complutense University of Madrid, Ciudad Universitaria, 28040 Madrid, Spain Department of Biochemistry and Molecular Biology, Faculty of Medicine, Institute of Medical Analysis in 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.) Department of Cell Biology, Faculty of Medicine, Institute of Healthcare Investigation at 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 function.Citation: Hurtado-Carneiro, V.; Dongil, P.; P ez-Garc , A.; varez, E.; Sanz, C. Stopping Oxidative Tension 5-HT Receptor Antagonist web inside the Liver: An Opportunity for GLP-1 and/or PASK. Antioxidants 2021, ten, 2028. doi.org/ 10.3390/antiox10122028 Academic Editors: Teresa Carbonell Cam and Joan RosellCatafauAbstract: The liver’s higher metabolic activity and detoxification functions create reactive oxygen species, mostly through oxidative phosphorylation inside the mitochondria of hepatocytes. In contrast, it also includes a potent antioxidant mechanism for counterbalancing the oxidant’s effect and relieving oxidative tension. PAS kinase (PASK) is really a serine/threonine kinase containing an N-terminal Per-ArntSim (PAS) domain, in a position to detect redox state. For the duration of fasting/feeding changes, PASK regulates the expression and activation of crucial liver proteins involved in carbohydrate and lipid metabolism and mitochondrial biogenesis. Interestingly, the functional inactivation of PASK prevents the development of a high-fat diet program (HFD)-induced obesity and diabetes. Also, PASK deficiency alters the activity of other nutrient sensors, for instance the AMP-activated protein kinase (AMPK) and also the mammalian target of rapamycin (mTOR). Additionally to the expression and subcellular localization of nicotinamide-dependent histone deacetylases (SIRTs). This review focuses on the partnership among oxidative stress, PASK, and also other nutrient sensors, updating the restricted know-how on the part of PASK inside 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 PARP14 site strain. The current know-how would suggest that PASK inhibition and/or exendin-4 remedy, particularly beneath fasting circumstances, could ameliorate problems associated with excess oxidative strain. Key phrases: exendin-4; metabolic sensors; antioxidantsReceived: 19 October 2021 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 a very important organ for adapting to nutritional changes (e.g., fasting/feeding states) by responding appropriately to achieve metabolic and energy homeostasis through its part inside the storage and redistribution of carbohydrates, proteins, vitamins, and lipids. 2. Liver Metabolic Functions and Detoxification Right after meals intake, the liver stores glucose as glycogen, facilitating glycemic manage [1]. Furthermore, the excess carbohydrate in carbohydrate-rich diets is converted into fatty acids through de novo lipogenesis [2,3]. By contrast, the liver produces glucose under fasting conditions, first by glycogenolysis and subsequently by way of hepatic