Activation of Pyruvate Dehydrogenase by Sodium Dichloroacetate Shifts Metabolic Consumption from Amino Acids to Glucose in IPEC-J2 Cells and Intestinal Bacteria in Pigs

• DOI: 10.1021/acs.jafc.7b05800
• Publication Date: 2018-02-23T05:48:19Z
• Authors: Rui An; Zhiru Tang; Yunxia Li; Tiejun Li; Qingqing Xu; Jifu Zhen; Feiru Huang; Jing Yang; Cheng Chen; Zhaoliang Wu; Mao Li; Jiajing Sun; Xiangxin Zhang; Jinchao Chen; Liuting Wu; Shengjun Zhao; Jiang Qingyan; Weiyun Zhu; Yulong Yin; Zhihong Sun
• Keywords: 0301 basic medicine; Bacteria; Dichloroacetic Acid; Swine; Pyruvate Dehydrogenase Complex; Cell Line; Intestines; 03 medical and health sciences; Glucose; Dietary Supplements; Animals; Amino Acids; Intestinal Mucosa; Pyruvates

The extensive metabolism of amino acids (AA) as fuel is an important reason for the low use efficiency of protein in pigs. In this study, we investigated whether regulation of the pyruvate dehydrogenase kinase (PDK)/pyruvate dehydrogenase alpha 1 (PDHA1) pathway affected AA consumption by porcine intestinal epithelial (IPEC-J2) cells and intestinal bacteria in pigs. The effects of knockdown of PDHA1 and PDK1 with small interfering RNA (siRNA) on nutrient consumption by IPEC-J2 cells were evaluated. IPEC-J2 cells were then cultured with sodium dichloroacetate (DCA) to quantify AA and glucose consumption and nutrient oxidative metabolism. The results showed that knockdown of PDHA1 using siRNA decreased glucose consumption but increased total AA (TAA) and glutamate (Glu) consumption by IPEC-J2 cells ( P < 0.05). Opposite effects were observed using siRNA targeting PDK1 ( P < 0.05). Additionally, culturing IPEC-J2 cells in the presence of 5 mM DCA markedly increased the phosphorylation of PDHA1 and PDH phosphatase 1, but inhibited PDK1 phosphorylation ( P < 0.05). DCA treatment also reduced TAA and Glu consumption and increased glucose depletion ( P < 0.05). These results indicated that PDH was the regulatory target for shifting from AA metabolism to glucose metabolism and that culturing cells with DCA decreased the consumption of AAs by increasing the depletion of glucose through PDH activation.