👤 Domenica Schiavone

This study investigated the hepatic expression of genes involved in stress response (CASP6, CAT, SOD1, HSPA2) and lipid metabolism (LPL, SREBF, FABP1, ACOX1, FADS2) in a local slow-growing chicken breed, the Bionda Piemontese (BP), following two isonitrogenous diets (crude protein, 170 g/kg as fed): a control diet (L) and a high-fat diet (H) obtained by supplementing 6 % palm kernel oil, during the finisher period. Sixty (male and female) chickens were included in the study and slaughtered at five months of age. RNA was extracted from 36 liver samples (18 male and 18 female) and sequenced using the targeted RNA-seq method followed by bioinformatic analysis using DESeq2 to detect differences in gene expression. Overall, the high-fat dietary supplementation did not significantly alter the expression of most stress-related genes, indicating that the high-fat diet did not elicit a hepatic stress response in BP chickens. However, within each sex, the high-fat diet tended to upregulate FADS2 and FABP1 in females, and slightly downregulate ACOX1 in males. Considering sex as an independent factor, FABP1 expression was higher in females, whereas males exhibited significantly higher LPL expression. These findings highlight a clear sexual dimorphism in hepatic lipid gene expression in BP chickens. While dietary fat supplementation had limited impact on differentially expressed genes, the study underscores the importance of sex in shaping metabolic gene expression. It also provides evidence supporting the possible metabolic resilience of the BP breed to tolerate changes in dietary fat content. Further studies are needed to substantiate this claim, and to investigate the long-term effects and the tissue-specific responses of dietary fat supplementation in other organs. Show less

Liver X receptors alpha and beta (LXRalpha, LXRbeta) are key regulators of cholesterol homeostasis. The effects of LXR ligands on endothelial cells are largely unknown. While oxysterol LXR agonists can increase the endothelial-leukocyte interaction, synthetic LXR agonists are anti-atherogenic and anti-inflammatory. Mechanistic differences may underlie such findings. LXRalpha and LXRbeta were found to be expressed in human endothelial cells. While synthetic LXR agonists could blunt the LPS-induced up-regulation of adhesion molecules (ICAM-1, VCAM-1, E-Selectin), 22-hydroxycholesterol and 24,25-epoxycholesterol enhanced such response. Microarray profiling further showed that the endothelial gene expression fingerprints of 22-hydroxycholesterol and T0901317 largely differed and unexpectedly shared only a restricted number of genes. Indeed, 22-hydroxycholesterol down-regulated eNOS and up-regulated a vast cohort of inflammatory mediators such as adhesion molecules, cytokines, enzymes and transcription factors. Other LXR-activating oxysterols such as 24,25-epoxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol could also stimulate the endothelial expression of inflammatory markers, although significant differences were observed. These effects persisted in LXR-silenced cells, confirming the mechanistic dissociation of oxysterol and LXR pathways. Furthermore, the oxysterol-induced expression of inflammatory markers was not secondary to cell apoptosis and may relate to oxidative stress. LXR-activating oxysterols comprehensively activate the expression of endothelial inflammation markers independently from LXRs. At proper dosage, synthetic LXR agonists are safe on endothelial cells and may even transrepress inflammatory reactions. Show less