Mechanistic Insight of Na/K-ATPase Signaling and HO-1 into Models of Obesity and Nonalcoholic Steatohepatitis

• Published in: International journal of molecular sciences Vol. 21; no. 1; p. 87
• Main Authors: Pratt, Rebecca, Lakhani, Hari Vishal, Zehra, Mishghan, Desauguste, Rutmann, Pillai, Sneha S, Sodhi, Komal
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-12-2019; MDPI
• Subjects: Adipocytes; Animals; Antioxidants; Apoptosis; Attenuation; Cell growth; Cytokines; Genotype & phenotype; Growth factors; Heme; Heme Oxygenase-1 - metabolism; Homeostasis; Humans; Inflammation; Kinases; Lipids; Metabolism; Mitochondria; Molecular modelling; Na+/K+-exchanging ATPase; Non-alcoholic Fatty Liver Disease - metabolism; Obesity; Obesity - metabolism; Oxidants; Oxidative Stress; Oxidizing agents; Oxygenase; Phenotypes; Proteins; Review; Signal Transduction; Sodium-Potassium-Exchanging ATPase - metabolism; Na/K-ATPase signaling; heme oxygenase 1; obesity; oxidative stress; non-alcoholic steatohepatitis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21010087

Obesity is a multifaceted pathophysiological condition that has been associated with lipid accumulation, adipocyte dysfunction, impaired mitochondrial biogenesis and an altered metabolic profile. Redox imbalance and excessive release of inflammatory mediators have been intricately linked in obesity-associated phenotypes. Hence, understanding the mechanisms of redox signaling pathways and molecular targets exacerbating oxidative stress is crucial in improving health outcomes. The activation of Na/K-ATPase/Src signaling, and its downstream pathways, by reactive oxygen species (ROS) has been recently implicated in obesity and subsequent nonalcoholic steatohepatitis (NASH), which causes further production of ROS creating an oxidant amplification loop. Apart from that, numerous studies have also characterized antioxidant properties of heme oxygenase 1 (HO-1), which is suppressed in an obese state. The induction of HO-1 restores cellular redox processes, which contributes to inhibition of the toxic milieu. The novelty of these independent mechanisms presents a unique opportunity to unravel their potential as molecular targets for redox regulation in obesity and NASH. The attenuation of oxidative stress, by understanding the underlying molecular mechanisms and associated mediators, with a targeted treatment modality may provide for improved therapeutic options to combat clinical disorders.