Abstract
Studies on animal models have demonstrated that feeding a low-arginine diet inhibits triacylglycerol (TAG) secretion from the liver, resulting in marked fatty liver development in rats. Here, we first showed that culturing hepatocytes in the medium mimicking the serum amino acid profile of low-arginine diet-fed rats induced TAG accumulation in the cells, indicating that the specific amino acid profile caused TAG accumulation in hepatocytes. Dietary adenine supplementation completely recovered hepatic TAG secretion and abolished hepatic TAG accumulation in rats. A comprehensive non-linear analysis revealed that inhibition of hepatic TAG accumulation by dietary adenine supplementation could be predicted using only serum amino acid concentration data. Comparison of serum amino acid concentrations indicated that histidine, methionine, and branched-chain amino acid (BCAA) concentrations were altered by adenine supplementation. Furthermore, when the serum amino acid profiles of low-arginine diet-fed rats were altered by modifying methionine or BCAA concentrations in their diets, their hepatic TAG accumulation was abolished. Altogether, these results suggest that an increase in methionine and BCAA levels in the serum in response to dietary arginine deficiency is a key causative factor for hepatic TAG accumulation, and dietary adenine supplementation could disrupt this phenomenon by altering serum amino acid profiles.
Highlights
Studies on animal models have demonstrated that feeding a low-arginine diet inhibits triacylglycerol (TAG) secretion from the liver, resulting in marked fatty liver development in rats
Among individuals with non-alcoholic fatty liver disease (NAFLD), many remain under benign conditions, whereas others exhibit non-alcoholic steatohepatitis (NASH) which can progress to liver inflammation, cirrhosis, and hepatocellular carcinoma[1,2]
Since it is known that dietary arginine deficiency alters nucleotide metabolism in the liver, thereby increasing orotic acid biosynthesis[8,9], some researchers have raised the possibility that fatty liver induced by a low-arginine diet may be caused by increased orotic acid[10]
Summary
Studies on animal models have demonstrated that feeding a low-arginine diet inhibits triacylglycerol (TAG) secretion from the liver, resulting in marked fatty liver development in rats. When the serum amino acid profiles of low-arginine diet-fed rats were altered by modifying methionine or BCAA concentrations in their diets, their hepatic TAG accumulation was abolished These results suggest that an increase in methionine and BCAA levels in the serum in response to dietary arginine deficiency is a key causative factor for hepatic TAG accumulation, and dietary adenine supplementation could disrupt this phenomenon by altering serum amino acid profiles. Since it is known that dietary arginine deficiency alters nucleotide metabolism in the liver, thereby increasing orotic acid biosynthesis[8,9], some researchers have raised the possibility that fatty liver induced by a low-arginine diet may be caused by increased orotic acid[10] In this case too, the detailed molecular mechanisms still remain unclear as to how modified nucleotide metabolism or the related metabolites alter the hepatic lipid metabolism. A mathematical non-linear analysis based on a machine learning method revealed that a comprehensive serum amino acid profile, but not individual amino acid concentrations, correlated well with hepatic TAG levels in a rat m odel[5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
