The Research Of Insulin Resistance Induced By High Levels Of NEFAs In The Adipocyte Of Dairy Cows

Perinatal cows were often in a state of negative energy balance induced by increased energy demand, growth and low dry matter intake, which further resulted in fat mobilization. Exssitive fat mobilization significantly induced high blood levels of NEFAs, and then induced fatty liver or ketosis. Importantly, the perinatal cows with negative energy balance presented low insulin sensitive index, and reflected by the less effect of insulin to the cell of cows, which further promoted the disorder of lipid metabolism. Insulin sighnaling pathways is combined with insulin and IR on the target cell membrane and tyrosine residues of IRS1 phosphorylation sites to activate the downstream PI3K/Akt signaling pathways to play a role of physiological cascade. Its IRS1 phosphorylation of tyrosine residues is the kepoint of insulin resistance, and the serine residues of phosphorylation sites of IRS1 further reduced its tyrosine phosphorylation, which further deduced the role of insulin. And ERS and mitochondrial dysfunction was associated with the insulin resistance, and could further induced IRS1 serine phosphorylation and block the insulin signal transmission, thereby inducing insulin resistance. However, the relationship between the high levels of NEFAs and the insulin resistance of cow adipose tissue and how NEFAs caused the insulin resistance of cow adipose cells was not reported. Therefore, this study wasstudied the relationship and induction mechanism between the NEFAs and insulin resistance in the cow adipose tissue suing the cow adipose cells.Cow adipose cells were treated with 0, 0.6, 1.2, and 2.4 mmol/L NEFAs, respectively. The results showed that IRS1 serine phosphorylation was enhanced and Akt phosphorylation was decresed with the increase of NEFAs concentration, which inducate that high concentrations of NEFAs could induce the insulin resistance in adipose cells. Furthermore, adipose cells treated with 2.4 mmol/L NEFAs for0.5 h, 1.5 h, 3 h, 5 h, 7 h, 12 h, and treaded 100 nmol/L insulin for 20 min. The results showed that the phosphorylation of IRS-1 serine residues was the highest in 3 h group.Adipose cells were treaded with different concentrations of NEFAs. The results found that NEFAs significantly increased PERK and IRE1 a phosphorylation in adipose cells. In addition, GRP78 and XBP-1s gene expression were also significantly increased. Thesehe results showed that high levels of NEFAs could induce ERS in the adipose cells. In addition, the results also showed that the protein expression of PGC-1?, Mfn2 and NRF-1 were significantly decreased. These results suggested that NEFAs could induce adipose cells mitochondrial dysfunction.TUDCA is an inhibitor of cells ERS, GW4064 is an agonist of PGC-1?. Adipose cells were treaded with TUDCA, GW4064, 2.4mmol/L NEFAs and 100nmol/L insulin, respectively. The experimental results show that TUDCA treatment could decreased the phosphorylation of PERK and IRE1? induced by NEFA. Furthermore, GW4064 treatment could increased the protein expression of PGC-1?, Mfn2 and the mRNA expression of GRP78, XBP-1s and PGC-1?. Importantly, the phosphorylation of IRS-1 serine was decreased. These results indicate that inhibition of endoplasmic reticulum stress and mitochondrial dysfunction induced by NEFAs can improve insulin resistance in fat cells.In conclusion, high concentration NEFAs caused insulin resistance, ERS, mitochondrial dysfunction. ERS and mitochondrial dysfunction is associated with the induction of insulin resistance induced by NEFA in cow adipose cells.