AMPK Activation and Lipid Homeostasis Regulation in MASLD: Investigating the Hepatoprotective and Anti-Inflammatory Effects of Meta-Capridin Medium-Chain Triglycerides

Metabolic dysfunction–associated steatotic liver disease (MASLD) is characterized by hepatic lipid accumulation, mitochondrial dysfunction, and chronic inflammation. Disruptions in fatty acid oxidation and ketogenesis contribute to disease progression, highlighting the potential of dietary interventions that enhance hepatic metabolic adaptation. This study investigates the effects of a medium-chain triglyceride supplement, meta-Capridin (m-CAP), on hepatic ketogenesis, mitochondrial function, and inflammatory responses in a MASLD rat model. Male Wistar rats were assigned to preventive and therapeutic groups and fed a normal diet, a high-fat diet (HFD), or a HFD supplemented with m-CAP. Key metabolic markers, including β-hydroxybutyrate, mitochondrial enzyme activity, peroxisome proliferator-activated receptor alpha (PPAR-α), AMP-activated protein kinase (AMPK), and LXR, were assessed alongside inflammatory cytokines and NLRP3 inflammasome activation. Results showed that m-CAP enhanced hepatic ketogenesis, increased AMPK phosphorylation, and upregulated PPAR-α, improving mitochondrial function. Additionally, it suppressed NLRP3 activation and proinflammatory cytokines, particularly in the therapeutic phase. These findings suggest that m-CAP promotes hepatic ketogenesis and modulates inflammation, supporting its potential as a functional food-based strategy for MASLD prevention and treatment.