GEF-H1 Mediated Control of NOD1 Dependent NF-κB Activation by Shigella Effectors

Shigella flexneri has evolved the ability to modify host cell function with intracellular active effectors to overcome the intestinal barrier. The detection of these microbial effectors and the initiation of innate immune responses are critical for rapid mucosal defense activation. The guanine nucleotide exchange factor H1 (GEF-H1) mediates RhoA activation required for cell invasion by the enteroinvasive pathogen Shigella flexneri. Surprisingly, GEF-H1 is requisite for NF-κB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-κB activation by H-Ala-D-γGlu-DAP (γTriDAP). GEF-H1 is essential for NF-κB activation by the Shigella effectors IpgB2 and OspB, which were found to signal in a NOD1 and RhoA Kinase (ROCK) dependent manner. Our results demonstrate that GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens

GEF-H1 Mediated Control of NOD1 Dependent NF-κB Activation by Shigella Effectors

Shigella flexneri has evolved the ability to modify host cell function with intracellular active effectors to overcome the intestinal barrier. The detection of these microbial effectors and the initiation of innate immune responses are critical for rapid mucosal defense activation. The guanine nucleotide exchange factor H1 (GEF-H1) mediates RhoA activation required for cell invasion by the enteroinvasive pathogen Shigella flexneri. Surprisingly, GEF-H1 is requisite for NF-κB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-κB activation by H-Ala-D-γGlu-DAP (γTriDAP). GEF-H1 is essential for NF-κB activation by the Shigella effectors IpgB2 and OspB, which were found to signal in a NOD1 and RhoA Kinase (ROCK) dependent manner. Our results demonstrate that GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens

Role of Corticosterone in Lipid Metabolism in Broiler Chick White Adipose Tissue

Excessive accumulation of body fat in broiler chickens has become a serious problem in the poultry industry. However, the molecular mechanism of triglyceride accumulation in chicken white adipose tissue (WAT) has not been elucidated. In the present study, we investigated the physiological importance of the catabolic hormone corticosterone, the major glucocorticoid in chickens, in the regulation of chicken WAT lipid metabolism. We first examined the effects of fasting on the mRNA levels of lipid metabolism-related genes associated with WAT, plasma corticosterone, and non-esterified fatty acid (NEFA). We then examined the effects of corticosterone on the expression of these genes in vivo and in vitro. In 10-day-old chicks, 3 h of fasting significantly decreased mRNA levels of lipoprotein lipase (LPL) in WAT and significantly elevated plasma concentrations of NEFA. Six hours of fasting significantly increased mRNA levels of adipose triglyceride lipase (ATGL) in WAT and significantly elevated plasma concentrations of corticosterone. On the other hand, fasting significantly reduced mRNA levels of LPL in WAT and elevated plasma concentrations of NEFA in 29-day-old chicks without affecting mRNA levels of ATGL in WAT or plasma corticosterone concentrations. Oral administration of corticosterone significantly reduced mRNA levels of LPL and significantly increased the mRNA levels of ATGL in WAT in 29-day-old chicks without affecting plasma NEFA concentrations. The addition of corticosterone to primary chicken adipocytes significantly increased mRNA levels of ATGL, whereas mRNA levels of LPL tended to decrease. NEFA concentrations in the culture medium were not influenced by corticosterone levels. These results suggest that plasma corticosterone partly regulates the gene expression of lipid metabolism-related genes in chicken WAT and this regulation is different from the acute elevation of plasma NEFA due to short-term fasting

Fasting and Glucagon Stimulate Gene Expression of Pyruvate Dehydrogenase Kinase 4 in Chickens

The excessive accumulation of body fat has become a serious problem in the broiler industry. However, the molecular mechanisms underlying the regulation of lipid metabolism-related genes in broiler chickens are not fully understood. In the present study, we investigated the role of glucagon on the expression of lipid metabolism-related genes in chicken white adipose tissue (WAT). Four hours of fasting significantly increased plasma levels of free fatty acid in broiler chickens. The mRNA levels of adipose triglyceride lipase (ATGL) and pyruvate dehydrogenase kinase 4 (PDK4) in abdominal WAT significantly increased by fasting, whereas the mRNA levels of diacylglycerol O-acyltransferase homolog 2 (DGAT2) and peroxisome proliferator-activated receptor-γ (PPARγ) significantly decreased. The results suggest that fasting stimulates lipolysis and suppresses adipogenesis and re-esterification of TG in chicken WAT. Glucagon significantly increased the mRNA levels of PDK4 in chicken primary adipocytes, whereas there were no significant changes in the mRNA levels of ATGL, DGAT2, and PPARγ. Our findings suggest that glucagon upregulates PDK4 expression and may stimulate lipolysis without affecting the expression of ATGL in chicken WAT