Vitamin K2 Alleviates Metabolic Dysfunction-Associated Steatotic Liver Disease Through Mitochondrial Dysfunction...

Area of Science:

• Hepatology
• Microbiology
• Nutritional Science

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) impacts one-third of the global population.
• Gut microbiota dysbiosis is linked to MASLD development.
• Vitamin K2 (VK2) shows potential in ameliorating mitochondrial dysfunction in MASLD models.

Purpose of the Study:

• To elucidate the mechanism by which VK2 modulates MASLD.
• To investigate the role of gut microbiota in VK2's therapeutic effects on MASLD.
• To explore VK2's impact on mitochondrial function and inflammatory pathways in MASLD.

Main Methods:

• Establishment of a MASLD mouse model using a high-fat diet (HFD).
• Administration of VK2 and assessment of liver histology, lipid levels, and inflammatory markers.
• 16S rRNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation (FMT) to analyze gut microbiota.
• Adeno-associated virus 9 (AAV9) mediated gene delivery to investigate molecular mechanisms.

Main Results:

• VK2 significantly reduced hepatic lipids (TG, TC) and liver enzymes (ALT, AST) in HFD-fed mice.
• VK2 suppressed inflammation, oxidative stress, and improved mitochondrial dysfunction in a gut microbiota-dependent manner.
• VK2 restored gut microbiota balance, increasing Lactobacillus abundance, and upregulated SIRT3 signaling pathway proteins.

Conclusions:

• VK2 demonstrates significant therapeutic potential for MASLD.
• The beneficial effects of VK2 are mediated through gut microbiota modulation, particularly enhancing Lactobacillus.
• VK2 ameliorates MASLD by improving mitochondrial dysfunction via the SIRT3 signaling pathway.