Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

Abstract

Background: Dietary protein deficiency and amino acid imbalance cause hepatic fat accumulation. We previously demonstrated that only arginine deficiency or total amino acid deficiency in a diet caused significant hepatic triglyceride (TG) accumulation in young Wistar rats. In this study, we explored the mechanisms of fatty liver formation in these models.Methods: We fed 6-week-old male Wistar rats a control diet (containing an amino acid mixture equivalent to 15% protein), a low-total-amino acid diet (equivalent to 5% protein; 5PAA), and a low-arginine diet (only the arginine content is as low as that of the 5PAA diet) for 2 weeks.Results: Much greater hepatic TG accumulation was observed in the low-arginine group than in the low-total-amino acid group. The lipid consumption rate and fatty acid uptake in the liver did not significantly differ between the groups. In contrast, the low-total-amino acid diet potentiated insulin sensitivity and related signaling in the liver and enhanced de novo lipogenesis. The low-arginine diet also inhibited hepatic very-low-density lipoprotein secretion without affecting hepatic insulin signaling and lipogenesis.Conclusions: Although the arginine content of the low-arginine diet was as low as that of the low-total-amino acid diet, the two diets caused fatty liver via completely different mechanisms. Enhanced lipogenesis was the primary cause of a low-protein diet-induced fatty liver, whereas lower very-low-density lipoprotein secretion caused low-arginine diet-induced fatty liver.

Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats

“…1c,d, Supplementary Table S3). While a ΔArg diet inhibited hepatic TAG secretion, resulting in fatty liver 13 , our results indicated that dietary adenine, but not guanine, fully rescued TAG secretion in the liver (Fig. 1e, f).…”

“…A previous study demonstrated that a low-protein/amino acid diet and a low-arginine diet resulted in significant fatty liver development 4,5 , which led to the assumption that dietary arginine intake could have an important role in NAFLD progression. However, dietary arginine intake did not correlate with hepatic TAG levels, and a low-amino acid diet and a low-arginine diet induced fatty liver through a different mechanism, although both diets contained the same amounts of arginine 13 . This suggests that dietary amino acid concentrations are not primarily important; instead, serum amino acids are associated with hepatic lipid metabolism.…”