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

• Main Authors: Lila Otani, Hiroki Nishi, Ayaka Koyama, Yuta Akasaka, Yusuke Taguchi, Yuka Toyoshima, Daisuke Yamanaka, Fumihiko Hakuno, Huijuan Jia, Shin-Ichiro Takahashi, Hisanori Kato
• Format: Article
• Language: English
• Published: BMC 2020-08-01
• Series: Nutrition & Metabolism
• Subjects: Arginine deficiency; Low-protein diet; Hepatosteatosis; Apolipoprotein A-IV; Insulin signaling
• Online Access: http://link.springer.com/article/10.1186/s12986-020-00477-5

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.