Abstract

Non-alcoholic fatty liver disorders (NAFLD) are defined by the accumulation of excess fat in the liver that has no other cause, such as drinking alcohol. Pyruvate dehydrogenase has been established as an alternative treatment for this disorder. NAFLD pathogenesis is complex and includes oxidative stress inflammatory processes and mitochondrial dysfunction. Impaired liver fatty acid oxidation and glucose oxidation are significant individuals in developing NAFLD, and strategies to reverse these defects can help alleviate the condition. A spectrum of liver diseases comprises NAFLD, which is currently referred to as metabolic dysfunction-associated liver disease (MASLD). The significant amounts of hepatocytes with minimal to no alcohol use hepatic steatosis disease indicates it. Over the next decade, NAFLD will overtake all other causes of cirrhosis due to its growing incidence, along with increased rates of obesity, metabolic syndromes, and, hence, prompting liver T2D transplantation. However, heart disease remains the leading cause of death, with a negligible proportion developing liver-related problems and fibrosis. To pathology, NAFLD is related to ergastoplasm stress, lipid toxicity, oxidative stress, and lipid depositions. Increased obesity and NAFLD, which is distinguished by the buildup of excess fat in the liver without alcohol abuse or other contributing factors like hepatitis C infection, are common in the public because of sedentary lifestyles and high-calorie consumption. Further, recent studies have demonstrated that, even while oxidative energy generation plays a minor role in the liver’s total glucose/ pyruvate metabolism, defects in glucose oxidation may potentially be a portion of the mitochondrial dysfunction in NAFLD. Therefore, hepatic steatosis can be reduced, and glucose homeostasis can be improved by reducing the defect in glucose oxidation. In this review, we will discuss the data supporting the role of reduced liver glucose oxidation in NAFLD pathogenesis and investigate the possibility of specifically targeting pyruvate dehydrogenase (PDH), the enzyme that limits the rate of glucose oxidation in NAFLD. We will also go over possible MOA for how elevated hepatic PDH activity and consequent glucose oxidation might cure the pathophysiology of obesity-induced NAFLD, as well as ways to target this pathway with therapeutic drugs.

Keyworde: Pyruvate dehydrogenase, therapeutic, NAFLD, diabetes mellitus, non-alcoholic fatty liver, oxidation stress

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