Effect of agonists of the G protein-coupled receptor 109A on the ketogenesis in primary hepatocytes

来源 :中国畜牧兽医学会兽医内科与临床诊疗学分会第八届代表大会暨学术研讨会 | 被引量 : 0次 | 上传用户:hummerandy
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  Ketosis or hyperketonemia,characterized by elevated levels of ketone bodies and NEFAs in the blood,is an important disease associated with negative energy balance (NEB) in dairy cow during the transition period from late gestation to early lactation.The excessive NEFA from fat mobilization due to NEB is metabolized,converted to ketone body(mainly β-hydroxybutyric acid,BHBA) in liver.HMGCS2 and HMGCL are the two main enzymes which involved in ketone body synthesis in liver.The GPR109A belongs to the family of hydroxy-carboxylic acid receptors and is activated by niacin(NC) as well by BHBA as the endogenous ligand.In this study,we evaluated the effect of the GPR 109As agonists (BHBA:0, 0.5, 1, 3 and 5 mM;NC:2, 8 and 32 μmol/L)on ketogenesis.mRNA and protein expression levels of HMGCS2 and HMGCL were detected in primary hepatocytes of bovine in vitro using qPCR and ELISA.The results showed that BHBA and NC decreased expression level of HMGCS2 and HMGCL in bovine hepatocytes in a dose-dependent manner,furthermore,high levels of BHBA or NC (exceeded 1 mmol/L and 32 μmol/L,respectively) can significantly inhibit expression of HMGCS2 and HMGCL (P<0.05),thus restricting ketone body production.Conclusion,the downregulation of HMGCS2 and HMGCL may be related to GPR109A activation by BHBA and NC.These findings implied feedback loops exist between BHBA concentration in plasma and ketogenesis in liver.
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