Branched-chain amino acids (BCAAs) promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals

Liver regeneration is one of the primary clinical importance in the setting of liver injury, resection, and transplantation [1],[2]. Although some amino acids are recognized to have favorable effects on the liver regeneration after partial hepatectomy (PH), molecular mechanisms underlying these effects are barely known [3].

We aimed to investigate the effects of valine, glutamine, and leucine amino acids on PH-induced NF-κB signal pathway.

Expressions of 8 genes involving in the NF-κB signal pathway was examined by an RT-PCR method in the liver tissue specimen. In our study, the effect of Leucine amino acid, a kind of Branched Chain Amino Acid (BCAA) on liver regeneration after PH in rats, was determined by RT-PCR, Western blot, and PCNA. Results showed that significantly decreased BCAA-induced upregulation of STAT-3, SOCS3, and NF-κB. However, IL-6 levels significantly increased in all groups.

In summary, demonstrating that BCAA enhances IL-6 proliferative signals in hepatocytes through down-regulation of SOCS3 while decreasing IL-6 levels and reducing its pro-inflammatory signals, all of which optimize liver regeneration. SOCS3 plays a dual role in modulating the rate of hepatocyte proliferation. In particular, this is the first demonstration of an endogenous mechanism to limit hepatocyte proliferation after injury.

Fig.1

• References

• 1 Fausto N. Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3. J. Exp. Med. 2008; 205: 91-103
• 2 Michalopoulos GK. Liver regeneration. J Cell Physiol. 2007; 213: 286-300
• 3 Cressman DE, Diamond RH, Taub R. Rapid activation of the Stat3 transcription complex in liver regeneration. Hepatology 1995; 21: 1443-1449.