Remote regulation of hepatic lipid secretion in the intestine by metabolic interaction of dietary arginine with ornithine.

The quantity and quality of dietary protein profoundly influence satiety, body growth, and systemic metabolism. Among the 20 major proteinogenic amino acids, arginine (Arg) is considerably associated with hepatic steatosis; when animals fed an Arg-deficient diet (ΔArg), triacylglyceride (TAG) dramatically accumulates in the liver. To explore the underlying mechanism, we first investigated the role of ornithine (Orn), as Orn is the primary metabolite of Arg and it is reportedly involved in the regulation of liver metabolism. While male Wistar rats fed a ΔArg diet exhibited a significant increase in liver TAG levels due to an attenuated TAG secretion, and consistently marked reduction of TAG-rich lipoproteins in the circulation, Orn addition to the diet completely abolished all these metabolic changes. Orn was only effective when taken orally, but not through intraperitoneal administration, suggesting that the intestine plays an essential role for Orn to regulate liver metabolism. The metabolic features similar to those of our rat model was also observed in the analyses of clinical samples, implying the common mechanism in humans. Conclusively, dietary Arg deficiency lowers local Arg-to-Orn conversion in the intestine, which in turn inhibits hepatic lipid secretion remotely via gut-liver axis.