L-Ornithine L-Aspartate for the Treatment of Sarcopenia in Chronic Liver Disease: The Taming of a Vicious Cycle
Figure 2
(a) Schematic representation of a vicious cycle by which hyperammonemia in cirrhosis resulting from diminished hepatic ammonia removal and portal-systemic shunting of venous blood results in muscle damage characterized by impairment of proteostasis and autophagy, the hallmarks of sarcopenia. Sarcopenia results in decreased capacity for ammonia removal by the muscle leading to enhancement of hyperammonemia and the cycle continues. (b) Treatment with LOLA results in reduction of hyperammonemia via metabolic and hepatoprotective mechanisms leading to a reduction of muscle damage and sarcopenia with consequent restoration of muscle glutamine synthesis, an additional mechanism implicated in the lowering of blood ammonia by LOLA in chronic liver disease. Direction and magnitude of changes in components of the cycle in this figure are indicated by arrows.