Effect Of Ketone Bodies And Non-Esterified Fatty Acids On Insulin Sensitivity In Diary Cows

High-yielding diary cows are often in a state of negative energy balanceat early milking time, severe negative energy balance leads to excessive mobilization of body fat, the metabolism of glucose and lipid become disordered, then Ketosis occurs. Insulin is one of the most important hormones regulating the metabolism of glucose and lipid, and plays an important role in the pathogenesis of ketosis. This study aims to clarify the state of insulin sensitivity in cows with ketosis and the effect of β-hydroxybutyrate (BHBA) and non-esterified acids (NEFA) on insulin signal in the liver and adipose tissue.In this experiment, 32 predelivery Holstein cows were selected, blood samples were collected from 1 week prepartum to 8weeks postpartum, the plasma levels of ketone body (KET)、non-esterified fatty acid (NEFA)、glucose (GLU)、insulin (INS) and insulin sensitivity index (RQUICKI) were detected. The plasma KET content of lOMg/dL was used as the standard, the cows were divided into ketosis group(K, KET≥10Mg/dL) and non-ketosis group(NK, KET<10Mg/dL).The dynamical changes of KET、NEFA、GLUT、INS and RQUICKI were analysised in K group and NK group, and the correlation of RQUICKI with other indexes was investigated. The results showed that the plasma levels of KET and NEFA of K group were significantly higher than those of NK group; the plasma INS level of K group was significantly higher than that of NK group. The RQUICKI of K group at 1 week prepartum and 4-8 weeks postpartum was significantly lower than NK group.Correlation analysis (n=320) showed that RQUICKI was very significantly correlated with NEFA(r= -0.383, P<0.001),GLU(r=-0.220, P<0.001), INS(r=-0.167, P<0.005).In vitro experiment, different concentrations of BHBA (0.5、1.0、 3.0、5.0 mM/L) and NEFA (0.4、0.8、1.6mmol/L) were used to treat the liver and subcutaneous adipose tissues of Holstein cows, and real-time flurescent quantitative PCR relative quantitative method was used to detect the INS receptor (InsR) and post-receptor signaling pathways critical factors IRS1, IRS2, p85 and GLUT4 mRNA relative expression. Results showed that high concentrations of BHBA and NEFA could significantly reduce the relative expression of IRS 1, IRS2, GLUT4 and InsR, and then leaded to a reduced insulin sensitivity of liver and adipose tissues. Liver and adipose tissues were more sensitive to the effect of NEFA.Conclusion, the insulin sensitivity in K cows is lower than that in NK cows, and the reduced insulin sensitivity is mainly related to the high level of plasma NEFA. High plasma levels of BHBA and NEFA in cows with ketosis may reduce the sensitivity of their liver and adipose tissue to insulin.