Increased FNDC5/Irisin expression in human hepatocellular carcinoma

Area of Science:

• Endocrinology
• Hepatology
• Oncology

Background:

• Fibronectin type III domain containing 5 (FNDC5)/Irisin is an energy-regulating hormone linked to lipid and carbohydrate metabolism.
• Hepatic FNDC5/Irisin expression in hepatocellular carcinoma (HCC), a condition with abnormal de novo lipogenesis (DNL), was previously unknown.
• HCC is characterized by aberrant DNL, involving complex regulatory pathways.

Purpose of the Study:

• To evaluate the gene expression of FNDC5/Irisin in HCC liver tissue.
• To investigate the association of FNDC5/Irisin with regulators of DNL, inflammation, and cancer progression in HCC.
• To explore the relationship between FNDC5/Irisin and plasma lipid profiles in HCC patients.

Main Methods:

• Gene expression analysis of FNDC5/Irisin and stearoyl-CoA desaturase 1 (SCD-1) in liver tissue from 18 HCC patients and 18 deceased donors.
• Evaluation of mRNA expression for key regulators including sterol regulatory element-binding factor 1, NOTCH1, tumor necrosis factor-α, and Interleukin-6.
• Correlation analysis between hepatic FNDC5/Irisin mRNA and plasma lipid profiles in HCC patients.

Main Results:

• Hepatic mRNA expression of FNDC5/Irisin and SCD-1 was significantly higher in HCC patients compared to donors.
• Hepatic NOTCH1 mRNA expression showed a trend towards higher levels in HCC patients.
• In HCC patients, FNDC5/Irisin mRNA strongly correlated with DNL regulators (SREBF1, SCD-1), NOTCH1, and inflammatory markers (TNF-α, IL-6), and tended to correlate with plasma lipid profiles.

Conclusions:

• Hepatocellular carcinoma liver tissue exhibits overexpression of FNDC5/Irisin.
• FNDC5/Irisin expression in HCC is linked to upregulated genes involved in lipogenesis, inflammation, and cancer progression.
• These findings suggest a potential protective role for FNDC5/Irisin in mitigating liver damage within the context of HCC.