Histidine Promotes the Glucose Synthesis through Activation of the Gluconeogenic Pathway in Bovine Hepatocytes.

Tianyu Yang,Kang Zhan,Maocheng Jiang,Guoqi Zhao,Osmond Datsomor,Xiaoyu Ma,Zhiqiang Cheng

doi:10.3390/ani11113295

Tianyu Yang, Kang Zhan + Show 5 more

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https://doi.org/10.3390/ani11113295

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Abstract

Simple SummaryThis study evaluated the effect of histidine (His) on hepatic glucose output and the expression of genes related to the gluconeogenic pathway in vitro. The results demonstrate that the supplementation of HIS can significantly improve the mRNA expression of phosphoenolpyruvate carboxykinase 1 (PCK1), phosphoenolpyruvate carboxykinase 2 (PCK2), fructose-1,6-bisphosphatase 1 (FBP1), and glucose-6-phosphatase (G6PC). Moreover, the addition of His ameliorated bovine hepatocytes glucose output. This study demonstrated that bovine hepatocytes can efficiently convert His into glucose to provide the energy required.Histidine (His) is considered to be the first-limiting amino acid (AA) on grass silage-based diets in lactation cows, which correlate positively with lactose yield. The higher glucose requirements of lactating cows can be met through a combination of increased capacity for gluconeogenesis and increased supply of gluconeogenic precursors. However, the effect of His on the expression of gluconeogenic genes in the bovine hepatocytes is less known. Therefore, this study aimed to investigate the regulatory effect of His on the key gluconeogenic genes and glucose output in bovine hepatocytes. The addition of 0.15, 0.6, and 1.2 mM His in a medium significantly enhanced (p < 0.05) the viability of bovine hepatocytes. Remarkably, 1.2 mM His induced profound changes (p < 0.05) in the mRNA level of key genes involved in gluconeogenesis, including PCK1, PCK2, FBP1, and G6PC in vitro. Furthermore, the mRNA expression of PCK1 was significantly elevated (p < 0.05) by the addition of 1.2 mM His at 3, 6, 12, and 24 h of incubation. The hepatic glucose output increased (p < 0.05) linearly with increasing His concentration. These findings indicate that the addition of His may be efficiently converted into glucose via the upregulation of genes related to the gluconeogenic pathway.

Highlights

Histidine (His) is the first-limiting amino acids (AA) on grass silage-based diets in lactation cows, which can remarkably enhance milk yield [1]
The expression of key genes involved in gluconeogenic pathway, including phosphoenolpyruvate carboxykinase 1 (PCK1), phosphoenolpyruvate carboxykinase 2 (PCK2), pyruvate carboxylase (PC), G6PC, and FBP1 were investigated using Quantitative Real-time PCR (qRT-PCR) (Figure 2 and Table 2)
At 3, 6, 12, and 24 h of incubation, His markedly upregulated (p < 0.05) the expression of PCK1 mRNA compared with the absence of His

Summary

Introduction

Histidine (His) is the first-limiting amino acids (AA) on grass silage-based diets in lactation cows, which can remarkably enhance milk yield [1]. Previous studies have reported that a sufficient proportion of His bypasses the rumen to increase the milk and lactose yield in lactating cows fed grass silage-based diets [4,5]. We were interested in testing whether an increase in lactose yield through His supplementation was due to gluconeogenic pathway activation, as propionate-induced gluconeogenesis has been previously explored [8]. The proportion of propionate involved in gluconeogenesis is between 50% and 60% in bovine hepatocytes [7] Supplementation with His increased lactose yield on grass silage-based diets in lactation cows with a low proportion of propionate in the rumen [1,4,5]

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