Elda Cristina Villaseñor-Tapia

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent global health concern driven by metabolic imbalance and excess caloric intake, leading to hepatic steatosis, inflammation, and fibrosis that may progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, or hepatocellular carcinoma. Current management relies primarily on lifestyle interventions and, in advanced stages, pharmacological therapies; however, long-term outcomes remain limited due to variable efficacy and poor sustainability. Recent advances in pharmacotherapy, including GLP-1 receptor agonists, THR-β agonists and SGLT2 inhibitors, have shown clinically meaningful improvements in metabolic parameters and hepatic steatosis, although their impact on fibrosis and long-term disease modification remains uncertain. In parallel, genomic and nanotechnology-based strategies (such as RNA-based therapies and nanoparticle delivery systems) have emerged as promising approaches to enhance drug stability, targeting, and therapeutic precision. Despite these advances, most emerging strategies remain at preclinical or early translational stages, with significant challenges related to safety, scalability, regulatory approval, and long-term efficacy. In this context, this review provides an integrative synthesis of pharmacological, genomic, and nanotechnology-based therapies, highlighting their mechanisms, limitations, and translational potential. Future research should focus on well-designed clinical trials, standardized evaluation frameworks, and the development of personalized therapeutic approaches. The convergence of these strategies may enable more effective and durable interventions for MASLD.

Metabolic dysfunction–associated steatotic liver disease (MASLD) is defined as the presence of excess triglyceride storage in the liver in the presence of at least one cardiometabolic risk factor. This term highlights the connection between fatty liver and metabolic dysfunction. Dietary factors, such as excessive consumption of saturated fats and sugar, contribute significantly to the accumulation of lipids in organs not specialized for fat storage, such as the liver. Hepatic lipid accumulation initiates dynamic changes in mitochondrial function and promotes the development and progression of MASLD. High‐fat, high‐fructose diet models have provided crucial insights into how nutritional factors induce mitochondrial dysfunction, which is characterized by impaired fatty acid oxidation, excessive generation of reactive oxygen species, and damage to mitochondrial DNA. Lifestyle modifications, including dietary adjustments such as calorie restriction and weight loss, are essential for the early prevention and long‐term treatment of MASLD. However, in recent years, several pharmacological options have emerged for the treatment of MASLD, primarily for the management of its comorbidities. This review explores the mechanisms of mitochondrial dysfunction promoted by the accumulation of hepatic lipids, analyzes the evidence of mitochondrial alterations in the liver of dietary models, and summarizes some of the main therapeutic interventions for MASLD and their effects on mitochondrial function.

Introduction. Chronic kidney disease (CKD) constitutes a chronic inflammatory state associated with an increase in inflammatory mediators and profibrotic molecules such as tumor necrosis factor‐α (TNF‐α). Etanercept (ETA) is a TNF inhibitor widely used in treatment of autoimmune inflammatory diseases. However, the effects of TNF‐α inhibition in the establishment of CKD have not been fully elucidated. We evaluate the effects of TNF inhibition by ETA in adenine‐ (Ad‐) induced CKD in rats. Methods. Rats were divided into three groups: control, renal injury model, and model plus ETA (2 mg/kg, 3 times per week (w); sc). Renal injury was induced by Ad administration (100 mg/kg, daily for 2 or 4 w; orogastric). Serum TNF‐α levels and biochemical parameters for renal function were evaluated. Histopathological changes in the kidney were assessed using H&E and Masson’s trichrome staining and also immunostaining for tubular cells. Results. Ad administration produced a renal functional decline, tubular atrophy, interstitial inflammation, and fibrosis for 2 w, followed by renal anemia, several renal dysfunctions, tubular atrophy, and fibrosis at 4 w. A significant increase in serum TNF‐α levels was observed from 2 w of Ad administration and remained elevated up to 4 w. Treatment with ETA partially reduced kidney damage but was very effective to blocking serum TNF‐α. Conclusion. Although inhibition of TNF by ETA was very effective in reducing serum TNF‐α, this strategy was partially effective in preventing Ad‐induced CKD.