Effect of lysine on afferent activity of the hepatic branch of the vagus nerve in normal and L-lysine-deficient rats

Amino acid deficiency was modeled by feeding rats a diet deficient in the essential L-amino acid, L-lysine (L-lys). There is a rapid anorectic response to such a diet, and a strong preference for L-lys develops during the deficiency. While the brain appears to trigger this preference, the peripheral pathways that inform the brain about the deficiency are not well understood. One possible information pathway may utilize an "amino acid sensor" in the hepatoportal region. In the present study, we measured in vivo neural activity in normal and L-lys-deficient rat. Compared to the normally fed controls, we found an approximately 100-fold increase in the firing sensitivity of the L-lys sensors in vagal afferent fibers from the hepatoportal region of the L-lys-deficient rats. Injection of 10 mM L-lys into the hepatoportal circulation, but not D-lysine (D-lys), evoked an increase in afferent activity. While L-lys deficiency enhanced the sensitivity of the L-lys sensors, the sensitivity due to other small amino acid sensors remained unchanged. Finally, we observed a time-dependent response of the lysine sensors to lysine deficiency. It required 3-4 days of maintenance on the lysine-deficient diet for the sensitivity of the L-lys sensors to change. Taken together, these results provide additional data to support the existence of putative L-amino acid sensors in the hepatoportal circulation. Additionally, they describe several characteristics of the L-lys sensors and show that these sensors may contribute to the adaptation to dietary L-lys deficiency and to maintenance of L-amino acid homeostasis.