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Insulin resistance (IR) is a critical factor of the pathophysiology of Gestational diabetes mellitus (GDM). Studies on key organs involved in IR, such as livers and adipose tissues, showed that Toll-like receptor 4 (TLR4) can regulate insulin sensitivity. As a maternal-fetal interface with multi-functions, placentae could contribute to the development of IR for GDM. Thus, we investigated the expressions of TLR4/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB) in term placentae from 33 GDM women and 36 healthy pregnant women with normal glucose tolerance, evaluated local and systemic IR and furthermore identified the association between placental TLR4 and IR. TLR4 protein was expressed in various cells of term placenta, particularly in syncytiotrophoblast of villi. Compared with normal pregnancy, the expression of TLR4/MyD88/NF-kB pathway increased in the placenta of GDM (p<0.05), and these differences were more pronounced in the maternal section of the placenta and the syncytiotrophoblast of villi. In addition, more severe IR was observed in the placenta of GDM patients than the control group, evidenced with higher pIRS-1(ser312) (p<0.001) and lower IRS-1 (p<0.05) as well as pAkt proteins (p<0.01). The expression of TLR4 in placentae is positively correlated with local IR (pIRS-1: r = 0.76, p <0.001 and pAkt: r = -0.47, p <0.001) and maternal fasting (r = 0.42, p <0.01), one-hour (r = 0.52, p <0.01) and two-hour glucose (r = 0.54, p <0.01) at OGTT. We found an that enhanced expression of the TLR4-MyD88-NF-kB pathway occurs in GDM placentae, which positively correlates with heightened local IR in placentae and higher maternal hyperglycemia. The TLR4/MyD88/NF-kB pathway may play a potential role in the development of IR in placentae of GDM.

The effects of two feeding regimens on meat quality, myosin heavy chain (MyHC) types, and key factors regulating muscle fiber type (AMP‐activated protein kinase [AMPK] and peroxisome proliferator‐activated receptor‐coactivator‐1α [PGC‐1α]) in the biceps femoris muscle of Mongolia sheep were investigated. A total of 20 Mongolia sheep were weaning for 90 days and divided into two groups (pasture group (P) and confinement group (C)) at 10.36 ± 0.35 kg of weaning weight. After weaning, sheep were pasture fed or confinement fed for 9 months. The results showed that live weights, carcass weight, intramuscular fat (IMF), and Warner–Bratzler shear force (WBSF) in P group were significantly lower (p <.05) than that in C group. Compared with P group, color evaluations with respect to L* and b* values were significantly higher (p <.05) in C group. Expression of the MyHC I gene in the P group was significantly higher, while MyHC IIa and MyHC IIb genes expression was significantly lower (p <.05) than that in C group. Also, AMPK activity and expression of AMPKα2 and PGC‐1α genes were significantly higher (p <.05) in P group compared with C group. The present study indicated that muscle fiber composition was one of the key differences leading to the differences of meat quality in different feeding regimens. AMPK, particularly AMPKα2, and PGC‐1α were considered to be two key factors regulating muscle fiber types in Mongolia sheep. The results support that AMPK activity and the expression of AMPKα2 and PGC‐1α genes may affect the composition of muscle fibers; thus, AMPK activity and the expression of AMPKα2 and PGC‐1α genes had an effect on meat quality by changed composition of muscle fibers. [ABSTRACT FROM AUTHOR]

Objective: Macrosomia is one of the most common complications in gestational diabetes mellitus. Insulin-like growth factor 2 and H19 are two of the imprinted candidate genes that are involved in fetal growth and development. Change in methylation at differentially methylated region of the insulin-like growth factor 2 and H19 has been proved to be an early event related to the programming of metabolic profile, including macrosomia and small for gestational age in offspring. Here we hypothesize that alteration in methylation at differentially methylated region of the insulin-like growth factor 2 and H19 is associated with macrosomia induced by intrauterine hyperglycemia. Results: The expression of insulin-like growth factor 2 is significant higher in gestational diabetes mellitus group (GDM group) compared to normal glucose tolerance group (NGT group) both in umbilical cord blood and placenta, while the expression of H19 is significant lower in GDM group in umbilical cord blood. The expression of insulin-like growth factor 2 is significant higher in normal glucose tolerance with macrosomia group (NGT-M) compared to normal glucose tolerance with normal birthweight group (NGT-NBW group) both in placenta and umbilical cord blood. A model with interaction term of gene expression of IGF2 and H19 found that IGF2 and the joint action of IGF2 and H19 in placenta showed significantly relationship with GDM/NGT and GDM-NBW/NGT-NBW. A borderline significant association was seen among IGF2 and H19 in cord blood and GDM-M/NGT-M. The methylation level at different CpG sites of insulin-like growth factor 2 and H19 in umbilical cord blood was also significantly different among groups. Based on the multivariable linear regression analysis, the methylation of the insulin-like growth factor 2 / H19 is closely related to birth weight and intrauterine hyperglycemia. Conclusions: We confirmed the existence of alteration in DNA methylation in umbilical cord blood exposed to intrauterine hyperglycemia and reported a functional role in regulating gene associated with insulin-like growth factor 2/H19. Both of these might be the underlying pathogenesis of macrosomia. We also provided the evidence of strong associations between methylation of insulin-like growth factor 2/H19 and macrosomia induced by intrauterine hyperglycemia. [ABSTRACT FROM AUTHOR]

Mass summer mortality events in the clam Meretrix petechialis resulting from Vibrio infection have occurred frequently in recent years, and seriously threaten the clam aquaculture industry. Metabolic processes are known to support host defense and survival in stressful conditions by regulating the allocation of metabolic resources. However, changes in lipid metabolism of clams in response to Vibrio infection are largely undescribed. In the present research, we characterized changes in key gene expression and enzyme activities associated with triglyceride-related metabolism, fatty acid de novo synthesis and fatty acid β-oxidation in M. petechialis during Vibrio infection. By mining dynamic transcriptome data before the increase in mortality, we found Vibrio infection caused significant changes in the metabolic regulations of carbohydrates, lipids, and amino acids. Our data show that levels of triglycerides (TG) decreased and free fatty acids (FFA) increased in the infected clams. Correspondingly, the synthesis activities of TG were significantly reduced relative to TG lipolysis activities after Vibrio infection. Additionally, FFA de novo synthesis was strengthened, especially before massive mortality occurred, but key genes of the fatty acid β-oxidation pathway showed no significant changes after Vibrio infection. We detected the expression of key genes related to lipid metabolism in resistant and susceptible clams under uninfected and infected conditions and found that differences in the basal expression of seven key genes (ATGL , MDY , SREBP , FAS , CPT-1 , ACS , and ECH) could be used as potential biomarkers to predict different Vibrio resistance in clams. Overall, our results provide a starting point for investigating the relationship between energy metabolism changes and the emergence of massive mortality induced by bacterial infection in clams. • The synthesis activities of TG were significantly reduced in clam after Vibrio infection. • FFA de novo synthesis was strengthened in clam after Vibrio infection. • The basal expression levels of 7 genes were identified to be significantly associated with Vibrio resistance. [ABSTRACT FROM AUTHOR]

Tanreqing injection (TRQ) is widely used, traditional Chinese medicine (TCM) injection used in China to treat respiratory infections. Modern pharmacological studies have confirmed that TRQ can protect against influenza viruses. However, the mechanism by which TRQ inhibits influenza viruses remains unclear. To explore the therapeutic effects and possible mechanisms of TRQ inhibition by the influenza virus. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was used to determine the chemical composition of TRQ. Isobaric tags for relative and absolute quantification (iTRAQ) were used to define differential proteins related to TRQ inhibition of viruses. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation. For experimental validation, we established an in vitro model of the influenza virus infection by infecting A549 cells with the virus. The detection of the signaling pathway was carried out through qPCR, western blotting,and immunofluorescence. Fifty one components were identified using UPLC/Q-TOF MS. We confirmed the inhibitory effect of TRQ on influenza virus replication in vitro. Ninety nine differentially expressed proteins related to the inhibitory effect of TRQ were identified using iTRAQ. KEGG functional enrichment analysis showed that the TRQ may inhibit influenza virus replication by affecting autophagy. Through network analysis, 29 targets were selected as major targets, and three key targets, HSPA5, PARP1, and GAPDH, may be the TRQ targets affecting autophagy. In vitro experiments showed that TRQ inhibits influenza virus replication by interfering with the expression and localization of STX17 and VAMP8 proteins, thereby promoting the fusion of autophagosomes with lysosomes. TRQ inhibits influenza virus replication by promoting the fusion of autophagosomes with lysosomes. We additionally established potential gene and protein targets which are affected by TRQ. Therefore, our findings provide new therapeutic targets and a foundation further studies on influenza treatment with TRQ. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights • Feeding regimens effected gene expression of FADS1 and FADS2 in adipose tissue. • The content of n-3 PUFA, especially EPA and DHA is higher in pastured sheep. • Different tissues have variable sensibilities to feeding regimens. Abstract The present study investigated the effects of two feeding regimens on meat quality, fatty acid profile and metabolism as it relates to gene expression in Sunit sheep. Two feeding regimens were used (pasture feeding and barn feeding, PF and BF) each containing 10 Sunit sheep. Results of this study indicated that PF sheep had significantly (P < 0.05) higher L* and b* values in their muscle compared to BF sheep. Also, the fatty acid composition of longissimus dorsi muscle and subcutaneous adipose tissues differed between feeding regimens. In this respect, concentrations of palmitic acid (C16:0) in the subcutaneous adipose tissue were significantly (P < 0.05) higher in BF sheep. Pastured sheep exhibited greater concentrations of polyunsaturated fatty acids (PUFA) including: linolenic acid (C18:3) (P < 0.001), DHA (P < 0.05), EPA (P < 0.001) and CLA cis-9, trans-11(P < 0.05) in their muscle compared to BF sheep. The expression of nine candidate genes related to fatty acid metabolism were analyzed by qPCR. In longissimus dorsi muscle, expression of acetyl CoA carboxylase (ACACA; P < 0.05) was up-regulated in BF sheep. Expression of the peroxisome proliferator activated receptor (PPARγ) (P < 0.05), stearoyl CoA desaturase (SCD) (P < 0.01), fatty acid desaturase1 (FADS1) (P < 0.05) and fatty acid desaturase 2 (FADS2) (P < 0.05) were up-regulated in PF sheep. Pasture feeding also increased (P < 0.05) expression of lipoprotein lipase (LPL), PPARγ, SCD, FADS1and fatty acid elongase 5 (Elove5) in the subcutaneous adipose tissue, however, the feeding regimens did not change expression of fatty acid synthase (FASN) and carnitine palmitoyl transferase I (CPT1). The results of this study indicated that the feeding regimen could be an important tool in manipulating the fatty acid profile of animal adipose tissue by altering the gene expression of enzymes involved in fat metabolism. [ABSTRACT FROM AUTHOR]