of Health-related Analysis at 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.) Department of Cell 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] 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. Stopping oxidative Stress within the Liver: An Opportunity for GLP-1 and/or PASK. Antioxidants 2021, 10, 2028. doi.org/ ten.3390/antiox10122028 Academic Editors: Teresa Carbonell Cam and Joan RosellCatafauAbstract: The liver’s high metabolic activity and detoxification functions produce reactive oxygen species, mainly by means of oxidative phosphorylation within the mitochondria of hepatocytes. In contrast, it also includes a potent antioxidant mechanism for counterbalancing the oxidant’s impact and relieving oxidative stress. PAS kinase (PASK) is usually a serine/threonine kinase containing an N-terminal Per-ArntSim (PAS) domain, able to detect redox state. In the course of fasting/feeding adjustments, PASK regulates the expression and activation of important 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 (HFD)-induced obesity and diabetes. Moreover, PASK deficiency alters the activity of other nutrient sensors, like the AMP-activated protein kinase (AMPK) plus the mammalian target of rapamycin (mTOR). In addition for the expression and subcellular localization of OX2 Receptor site nicotinamide-dependent histone deacetylases (SIRTs). This critique focuses on the partnership between oxidative strain, PASK, along with other nutrient sensors, updating the restricted expertise N-type calcium channel manufacturer 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 damage connected with hepatic oxidative tension. The present expertise would recommend that PASK inhibition and/or exendin-4 therapy, especially below fasting conditions, could ameliorate issues linked with excess oxidative pressure. 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 often a crucial organ for adapting to nutritional alterations (e.g., fasting/feeding states) by responding appropriately to achieve metabolic and power homeostasis by way of its function in the storage and redistribution of carbohydrates, proteins, vitamins, and lipids. two. Liver Metabolic Functions and Detoxification Following food intake, the liver retailers glucose as glycogen, facilitating glycemic manage [1]. In addition, 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 below fasting conditions, 1st by glycogenolysis and subsequently by means of hepatic
