Emerging natural products against obesity and metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis: Direct target discovery and mechanistic insight

4 hours ago

Obesity is a multifactorial metabolic condition linked to lipid dysregulation and energy imbalance, driving global prevalence.
Obesity leads to serious comorbidities like metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), key causes of liver-related morbidity.
Pathophysiological shared factors include insulin resistance, chronic inflammation, and mitochondrial dysfunction, creating a cycle where obesity worsens hepatic steatosis and fibrosis.
FDA-approved treatments like GLP-1 receptor agonists (e.g., semaglutide) show weight loss efficacy but have limitations like gastrointestinal intolerance and variable liver outcomes.
Recent approval of resmetirom for MASH addresses some needs but faces challenges in durability, accessibility, and adverse effects such as gastrointestinal reactions.
Natural products, due to their structural diversity and multitarget potential, offer promising therapeutic avenues for dual intervention in obesity-MASLD/MASH.
The review evaluates emerging endogenous metabolites and plant-derived compounds, focusing on their directly validated molecular targets and preclinical evidence for metabolic reprogramming.
It integrates translational insights from natural product research and clinical trials of related synthetic agonists to advance frameworks for managing obesity and MASLD/MASH concurrently.

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