SIRT6, a New Hope in Liver Diseases: From Pathogenic Mechanisms to Therapeutic Strategies

Area of Science:

• Hepatology
• Molecular Biology
• Biochemistry

Background:

• Liver diseases cause 2 million deaths annually, representing a significant global health burden.
• The NAD-dependent deacetylase SIRT6 is implicated in critical liver physiological and pathological processes.
• Understanding SIRT6's role is crucial for developing new therapeutic strategies for liver disorders.

Purpose of the Study:

• To review the multifaceted role of SIRT6 in hepatic physiology and pathology.
• To emphasize SIRT6's regulatory mechanisms in lipid metabolism, inflammation, and oxidative stress.
• To explore SIRT6's involvement in various liver diseases and potential therapeutic activations.

Main Methods:

• Literature review focusing on SIRT6's functions in the liver.
• Analysis of SIRT6's regulatory pathways in lipid metabolism, inflammation, and oxidative stress.
• Examination of SIRT6's role in liver fibrosis, NAFLD, and liver cancer.

Main Results:

• SIRT6 maintains hepatic lipid homeostasis and regulates hepatic inflammation and oxidative stress.
• SIRT6 alleviates liver diseases including liver fibrosis, non-alcoholic fatty liver disease (NAFLD), and liver cancer.
• Natural and chemical activators (e.g., MDL-800, diosgenin) can enhance SIRT6 activity or expression, improving liver damage.

Conclusions:

• SIRT6 plays a critical protective role in liver health.
• Targeting SIRT6 offers a promising therapeutic avenue for diverse liver disorders.
• Activation of SIRT6 presents a potential strategy for novel liver disease treatments.