Dietary arginine affects the insulin signaling pathway, glucose metabolism and lipogenesis in juvenile blunt snout bream Megalobrama amblycephala

Abstract

This study evaluated the mechanisms governing insulin resistance, glucose metabolism and lipogenesis in juvenile fish fed with graded levels of dietary arginine. The results showed that, compared with the control group (0.87%), 2.31% dietary arginine level resulted in the upregulation of the relative gene expression of IRS-1, PI3K and Akt in the insulin signaling pathway, while 2.70% dietary arginine level led to inhibition of these genes. 1.62% dietary arginine level upregulated glycolysis by increasing GK mRNA level; 2.70% dietary arginine level upregulated gluconeogenesis and resulted in high plasma glucose content by increasing PEPCK and G6P mRNA level. Furthermore, 2.70% dietary arginine level significantly lowered GLUT2 and increased PK mRNA levels. 1.62% dietary arginine level significantly upregulated ACC, FAS and G6PDH mRNA levels in the fat synthesis pathway and resulted in high plasma TG content. These results indicate that 1.62% dietary arginine level improves glycolysis and fatty acid synthesis in juvenile blunt snout bream. However, 2.70% dietary arginine level results in high plasma glucose, which could lead to negative feedback of insulin resistance, including inhibition of IRS-1 mRNA levels and activation of gluconeogenesis-related gene expression. This mechanism seems to be different from mammals at the molecular level.

Figure 1

Relative expressions of insulin signaling pathway. Such as IRS-1 (A), PI3K (B) and Akt (C) genes in the liver of blunt snout bream fed diets with different arginine levels. Data are expressed as means with SEM. Value with different superscripts are significantly different (P < 0.05).

Figure 2

Relative expressions of glucose metabolism signaling pathway. Such as GK (A), PK (B), PEPCK (C), G6P (D), GS (E), and GLUT 2 (F) genes in the liver of blunt snout bream fed diets with different arginine levels. Data are expressed as means with SEM. Value with different superscripts are significantly different (P < 0.05).

Figure 3

Plasma glucose (A) liver glycogen (B) and plasma insulin (C) contents of blunt snout bream fed diets with different arginine levels. Data are expressed as means with SEM. Value with different superscripts are significantly different (P < 0.05).

Figure 4

Relative expressions of lipid metabolism signaling pathway. Such as (A) FAS, (B) ACC, (C) G6PDH genes in the liver of blunt snout bream fed diets with different arginine levels. Data are expressed as means with SEM. Value with different superscripts are significantly different (P < 0.05).

Figure 5

Plasma cholesterol (A) and triglyceride (B) contents of blunt snout bream fed diets with different arginine levels. Data are expressed as means with SEM. Value with different superscripts are significantly different (P < 0.05).

Figure 6

Glucose and lipid metabolism signaling pathway. Optimal dietary arginine level (1.62%) elevated the relative expression of Glucokinase (GK); Glucose-6-phosphate dehydrogenase (G6PDH); Fatty acid synthase (FAS); Acetyl CoA carboxylase (ACC). High dietary arginine level (2.70%) increased the relative gene expressions of Phosphoenolpyruvate carboxykinase (PEPCK); Glucose 6-phosphatase (G6P) and Pyruvate kinase (PK); lowered Glucose transporter 2 (GLUT 2).

Figure 7

Insulin signaling pathway. Excess dietary arginine level (2.70%) resulted in protein S6 kinase 1 (S6K1) was over-expressed, which led to negative feedback in insulin resistance including inhibition of Insulin receptor substrate 1 (IRS-1); Phosphoinositide 3-kinase (PI3K) and Protein kinase B (Akt).