THE MOLECULAR MECHANISMS OF HEPATIC STEATOSIS AND ITS RELATIONSHIP WITH CARBOHYDRATE AND LIPID METABOLISM
The Molecular Mechanisms of Hepatic Steatosis
Keywords:
Hepatic steatosis, Lipid metabolism, Metabolic dysfunction-associated steatotic liver disease (MASLD), Oxidative stress.Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent form of liver disease worldwide, affecting approximately one-quarter of the global population. It is characterized by hepatic fat accumulation (steatosis) and is linked to increased morbidity, comorbidities, and mortality. Objectives: This review aims to explore the molecular mechanisms underlying hepatic steatosis in MASLD, with a particular focus on the metabolic pathways involved in lipid and carbohydrate dysregulation. Methods: A narrative review of current literature was conducted to examine the interplay between lipid influx, fatty acid oxidation, lipid export, and oxidative stress in the pathogenesis of MASLD. Special emphasis was placed on the compensatory and maladaptive responses of the liver’s metabolic pathways. Results: In MASLD, increased fatty acid uptake and de novo lipogenesis exceed the liver’s capacity for fatty acid oxidation and lipid export. While compensatory mechanisms initially upregulate lipid oxidation and export, these become insufficient as disease progresses. This imbalance contributes to oxidative stress through impaired mitochondrial function, as well as enhanced peroxisomal and cytochrome P450-mediated oxidation. The resulting lipid accumulation triggers lipoapoptosis, driving both hepatic injury and systemic metabolic dysfunction. Conclusions: Dysregulated hepatic lipid metabolism in MASLD fosters oxidative stress and cellular injury, thereby promoting disease progression and contributing to associated comorbidities such as cardiovascular disease, diabetes, and obesity. Understanding these mechanisms may inform the development of targeted therapeutic strategies.
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