Endocrine Abstracts

Leptin circulates as a free (FL) and a protein-bound (BL) form, with the soluble leptin receptor (LR) as an important binding compound. This study was set out to address the distinct role of the leptin components in the metabolic and inflammatory tissue-repair response in patients with liver cirrhosis.

Methods

We investigated hepatic substrate and leptin metabolism in 40 cirrhotics employing a combination of arterial and hepatic vein catheterisation technique and hepatic blood flow measurements. Next to metabolic, inflammatory, and neuroendocrine parameters, FL, BL, and sLR were determined by specific radioimmunassays.

Results

Whereas Fl was not increased, BL and sLR were significantly elevated in cirrhotics compared to matched controls. BL was correlated to sLR only in cirrhotics (r=0.70,P<0.001). FL was linked to metabolic parameters like energy storage (body fat mass; r=0.36, P<0.05), insulin and insulin resistance (r=0.48; r=0.46, P<0.01) as well as hepatic glucose and energy release (r=0.35 and r=0.40, P<0.05). In contrast, BL and sLR were linked to proinflammatory cytokines and sympathetic activity (r=0.61 and r=0.56, P<0.01). In addition, we found evidence, that the liver may be involved in generation of sLR and BL.

Conclusion

Our data suggest that the components of the leptin system FL, BL, and sLR have distinct roles in metabolic and inflammatory processes in patients with liver cirrhosis and that the liver is capable to modulate the leptin system and its biological capacity. The better understanding of this metabolic and inflammatory tissue-repair response may lead to innovative new therapy strategies in liver disease.