Intrauterine growth restriction in piglets modulates postnatal immune function and hepatic transcriptional responses independently of energy intake.

Introduction: Insufficient prenatal nutrition can affect fetal development and lead to intrauterine growth restriction (IUGR). The aim of this study was to investigate hepatic transcriptional responses and innate immune function in piglets suffering from IUGR compared to normal-sized piglets at 3 days of age and explore whether the provision of an energy-rich supplement at birth could modulate these parameters. Methods: A total of 68 piglets were included in the study. Peripheral blood mononuclear cells were harvested for LPS stimulation, and organs were harvested post-mortem to quantify relative weights. Liver tissue was utilized for RNA sequencing coupled with gene-set enrichment analysis. Results: IUGR resulted in increased expression of genes such as PDK4 and substantial alterations in transcriptional pathways related to metabolic activity (e.g., citric acid and Krebs cycles), but these changes were equivalent in piglets given an energy-rich supplement or not. Transcriptomic analysis and serum biochemistry suggested altered glucose metabolism and a shift toward oxidation of fatty acids. IUGR piglets also exhibited suppression of genes related to innate immune function (e.g., CXCL12) and pathways related to cell proliferation (e.g., WNT and PDGF signaling). Moreover, they produced less IL-1ß in response to LPS stimulation and had lower levels of blood eosinophils than normal-sized piglets. Discussion: Taken together, our results indicate that IUGR results in early-life alterations in metabolism and immunity that may not be easily restored by the provision of exogenous energy supplementation.

CYP2A6 polymorphisms are associated with nicotine dependence and influence withdrawal symptoms in smoking cessation.

CYP2A6 is the main enzyme that catalyzes nicotine into cotinine. Interindividual differences in nicotine metabolism result at least partially from polymorphic variation of CYP2A6 gene. In this study, we evaluated the influence of CYP2A6 polymorphisms on clinical phenotypes of smoking, such as smoking habit and withdrawal symptoms. Japanese smokers (n = 107) were genotyped for CYP2A6*1, *4 and *9. Consistent with the previous reports, CYP2A6 genotypes have a tendency to correlate with the number of cigarettes per day and with daily intake of nicotine. Interestingly, CYP2A6 high-activity group (CYP2A6*1/*1, *1/*9, *1/*4, *9/*9) smoked the first cigarette of the day earlier than low-activity group (CYP2A6*4/*9, *4/*4), indicating more remarkable nicotine dependence. Furthermore, nicotine withdrawal symptoms were more serious in smoking cessation in CYP2A6 high-activity group. Collectively, CYP2A6 genotypes are related with nicotine dependence, influencing smoking habits and withdrawal symptoms in quitting smoking. It is proposed that individualized smoking cessation program could be designed based on CYP2A6 genotypes.