Changes in the expression of hypothalamic lipid sensing genes in rat model of intrauterine growth retardation (IUGR).
ABSTRACT Intrauterine growth retardation (IUGR) has been linked to the development of type 2 diabetes in later life. The mechanisms underlying this phenomenon are unknown. Recent data suggest that some of the molecular defects underlying type 2 diabetes reside in the CNS. The enzyme carnitine palmitoyltransferase-1 (CPT1) regulates long-chain fatty acid (LCFA) entry into mitochondria, where LCFA undergo beta-oxidation. Hypothalamic inhibition of CPT1 decreases food intake and suppresses endogenous glucose production. Our aim was to investigate the effects of uterine artery ligation, a procedure that mimics uteroplacental insufficiency, on the CNS expression of CPT1 and other key enzymes of LCFA metabolism. Bilateral uterine artery ligation was performed on d 19 of gestation in the pregnant rat; sham-operated pregnant rats served as controls. Hypothalamus, cerebellum, hippocampus, and cortex were dissected and analyzed at birth by real-time PCR. Nonesterified fatty acid (NEFA) serum levels were significantly higher in IUGR pups (p<0.0001). In IUGR rats, the hypothalamic expression of CPT1 isoform C (p=0.005) and acetyl-CoA carboxylase (ACC) isoforms alpha (p<0.05) and beta (p=0.005) were significantly decreased. The data presented here support the hypothesis that an abnormal intrauterine milieu can induce changes in hypothalamic lipid sensing.
Full-textDOI: · Available from: Daniela Germani, Apr 15, 2014
SourceAvailable from: onlinelibrary.wiley.com[Show abstract] [Hide abstract]
ABSTRACT: This represents an overview of the use of animal models to study the adverse pregnancy outcomes seen in humans. The purpose is to entice clinicians to utilize some of this information to seek out the literature and have more meaningful and profitable discussions with their academic colleagues and enhance transdisciplinary research in reproductive health.American Journal Of Reproductive Immunology 02/2013; DOI:10.1111/aji.12102 · 3.32 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Intrauterine growth retardation predisposes toward long-term morbidity from type 2 diabetes and cardiovascular disease. To explain this association, the concept of programming was introduced to indicate a process whereby a stimulus or insult at a critical period of development has lasting or lifelong consequences on key endocrine and metabolic pathways. Subtle changes in cell composition of tissues, induced by suboptimal conditions in utero, can influence postnatal physiological functions. There is increasing evidence, suggesting that liver may represent one of the candidate organs targeted by programming, undergoing structural, functional and epigenetic changes following exposure to an unfavorable intrauterine environment. The aim of this review is to provide insights into the molecular mechanisms underlying liver programming that contribute to increase the cardiometabolic risk in subjects with intrauterine growth restriction.International journal of obesity (2005) 04/2012; 36(10):1270-7. DOI:10.1038/ijo.2012.54 · 5.39 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The purpose of this study was to investigate alterations in brain metabolism in fetuses with intrauterine growth restriction (IUGR) and evidence of cerebral redistribution of blood flow. Biometry and Doppler assessment of blood flow was assessed with ultrasound in 28 fetuses with IUGR and cerebral redistribution and in 41 appropriately grown control subjects. Proton magnetic resonance spectroscopy of the fetal brain was then performed to determine the presence of choline (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate and to generate ratios for NAA:Cho, NAA:Cr, and Cho:Cr. Sixty-five percent of spectra were interpretable: N-acetylaspartate, choline, and creatine peaks were identified in all these spectra; lactate was present in 5 IUGR fetuses and in 3 appropriately grown fetuses. NAA:Cr and NAA:Cho ratios were significantly lower in IUGR fetuses with cerebral redistribution. Cerebral redistribution is associated with altered brain metabolism that is evidenced by a reduction in NAA:Cho and NAA:Cr ratios.American journal of obstetrics and gynecology 06/2011; 205(5):483.e1-8. DOI:10.1016/j.ajog.2011.06.032 · 3.97 Impact Factor