Adapter proteins regulate insulin resistance and lipid metabolism in obesity

Insulin resistance and dysregulated lipid meta- bolism are major causes of type 2 diabetes. Insulin and inflam- matory signal pathways play key roles in insulin resistance and fat accumulation. Specifically, adapter proteins transduce sig- nals from insulin or cytokine receptors to the downstream pathways and may contribute to insulin resistance and disor- dered lipid metabolism in obesity and type 2 diabetes. Here, the recent advances in understanding the roles of adapter proteins in insulin resistance and lipid homeostasis are discussed.

Adapter proteins regulate insulin resistance and lipid metabolism in obesity

Insulin resistance and dysregulated lipid metabolism are major causes of type 2 diabetes. Insulin and inflammatory signal pathways play key roles in insulin resistance and fat accumulation. Specifically, adapter proteins transduce signals from insulin or cytokine receptors to the downstream pathways and may contribute to insulin resistance and disordered lipid metabolism in obesity and type 2 diabetes. Here, the recent advances in understanding the roles of adapter proteins in insulin resistance and lipid homeostasis are discussed.

Relationship between the expression of TLR4 and TIRAP and sepsis in peripheral blood

Objective:To explore the relationship between the expression of TLR4 and TIRAP and sepsis severity.Methods:The study selected 30 healthy examinees as the control group and 53 patients with sepsis as the observation group.The patients in the observation group were assessed by Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ).40 patients with APACHE Ⅱ score≤20,were classified into the low-score sepsis group;13 patients with APACHE Ⅱ score>20,were classified into the high-score sepsis group.The levels of TLR4 and TIRAP in venous serum were detected in all subjects by enzyme-linked immunosorbent assay(ELISA).Results:The levels of TLR4 and TIRAP in serum were 0.886±0.058 ng/ml and 5.216±0.410 ng/ml in the control group;2.253±0.379 ng/ml and 9.540±2.294 ng/ml in the low-score sepsis group;4.494±0.709 ng/ml and 19.206±1.755 ng/ml in the high-score sepsis group.The observation group(low-score and high-score sepsis groups)was significantly different from the control group(p=.000),and the low-score sepsis group was significantly different from the high-score sepsis group(p=.000).With APACHE II score of 20 as the cut-off point,the low-score sepsis group was consisted of low-risk patients and the high-score group was consisted of the high-risk,which can indicate the sepsis severity.According to Pearson’s correlation analysis,the level of TLR4 was positively correlated with sepsis severity(r=0.931,p<.05),the level of TIRAP was also positively correlated with the sepsis severity(r=0.972,p<.05);the level of TLR4 was positively correlated with the level of TIRAP(r=0.936,p<.05).Conclusions:The levels of TLR4 and TIRAP in septic patients can be used to predict and determine the severity of sepsis.

Breed and adaptive response modulate bovine peripheral blood cells＇ transcriptome

Background： Adaptive response includes a variety of physiological modifications to face changes in external or internal conditions and adapt to a new situation. The acute phase proteins（APPs） are reactants synthesized against environmental stimuli like stress, infection, inflammation.Methods： To delineate the differences in molecular constituents of adaptive response to the environment we performed the whole-blood transcriptome analysis in Italian Holstein（IH） and Italian Simmental（IS） breeds. For this, 663 IH and IS cows from six commercial farms were clustered according to the blood level of APPs. Ten extreme individuals（five APP＋ and APP-variants） from each farm were selected for the RNA-seq using the Illumina sequencing technology. Differentially expressed（DE） genes were analyzed using dynamic impact approach（DIA）and DAVID annotation clustering. Milk production data were statistically elaborated to assess the association of APP＋ and APP-gene expression patterns with variations in milk parameters.Results： The overall de novo assembly of cDNA sequence data generated 13,665 genes expressed in bovine blood cells. Comparative genomic analysis revealed 1,152 DE genes in the comparison of all APP＋ vs. all APP-variants; 531 and 217 DE genes specific for IH and IS comparison respectively. In all comparisons overexpressed genes were more represented than underexpressed ones. DAVID analysis revealed 369 DE genes across breeds, 173 and 73 DE genes in IH and IS comparison respectively. Among the most impacted pathways for both breeds were vitamin B6 metabolism, folate biosynthesis, nitrogen metabolism and linoleic acid metabolism.Conclusions： Both DIA and DAVID approaches produced a high number of significantly impacted genes and pathways with a narrow connection to adaptive response in cows with high level of blood APPs. A similar variation in gene expression and impacted pathways between APP＋ and APP-variants was found between two studied breeds. Such similarity was also confirmed by annotation clustering of the DE genes. However, IH breed showed higher and more differentiated impacts compared to IS breed and such particular features in the IH adaptive response could be explained by its higher metabolic activity. Variations of milk production data were significantly associated with APP＋ and APP-gene expression patterns.