of Medical Investigation at 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 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 work.Citation: Hurtado-Carneiro, V.; Dongil, P.; P ez-Garc , A.; varez, E.; Sanz, C. Preventing Oxidative Pressure inside the Liver: An Opportunity 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, primarily by way of oxidative phosphorylation within the mitochondria of hepatocytes. In contrast, additionally, it features a potent antioxidant mechanism for counterbalancing the oxidant’s impact and relieving oxidative anxiety. PAS kinase (PASK) is usually a serine/threonine kinase containing an N-terminal Per-ArntSim (PAS) domain, in a position to detect redox state. Through fasting/feeding alterations, PASK regulates the expression and activation of important liver proteins involved in carbohydrate and lipid α adrenergic receptor Purity & Documentation metabolism and mitochondrial biogenesis. Interestingly, the functional inactivation of PASK prevents the development of a high-fat diet program (HFD)-induced obesity and diabetes. Moreover, PASK deficiency alters the activity of other nutrient sensors, which include the AMP-activated protein kinase (AMPK) plus the PARP2 supplier mammalian target of rapamycin (mTOR). In addition towards the expression and subcellular localization of nicotinamide-dependent histone deacetylases (SIRTs). This assessment focuses around the relationship amongst oxidative pressure, PASK, and other nutrient sensors, updating the limited knowledge around the function of PASK within the antioxidant response. We also comment on glucagon-like peptide 1 (GLP-1) and its collaboration with PASK in stopping the harm related with hepatic oxidative anxiety. The existing know-how would recommend that PASK inhibition and/or exendin-4 therapy, specially below fasting circumstances, could ameliorate problems linked with excess oxidative anxiety. Keywords: 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 crucial organ for adapting to nutritional adjustments (e.g., fasting/feeding states) by responding appropriately to attain metabolic and power homeostasis by means of its part 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 handle [1]. Furthermore, the excess carbohydrate in carbohydrate-rich diets is converted into fatty acids by way of de novo lipogenesis [2,3]. By contrast, the liver produces glucose beneath fasting conditions, initially by glycogenolysis and subsequently via hepatic