Biology subjects

Regnault, T. R. H.

Publications and source records attributed to Regnault, T. R. H..

3 recordsLinked to original sources

bioRxiv2023

Quantifying Myelin Water Fraction in a Guinea Pig Model of Spontaneous Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is an obstetrical outcome where a fetus has not achieved its genetic potential. A consequence of IUGR is a decrease in brain myelin content. Myelin water imaging (MWI) has previously assessed fetal myelin water fraction (MWF) and can potentially assess myelination changes associated with IUGR. Thus, this study aims to quantify and compare the MWF of non-IUGR and IUGR fetal guinea pigs (GPs) in late gestation. Our sample consisted of 22 pregnant Dunkin-Hartley GPs with 71 fetuses (34 male) [mean {+/-} standard deviation: 60 {+/-} 1.2 days gestation]. Eight SPGR volumes [flip angles (): 2{degrees} - 16{degrees}], and two sets of 8 bSSFP volumes (: 8{degrees} - 64{degrees}), at 0{degrees} and 180{degrees} phase increments were acquired at 3.0 T. MWF maps were generated for each fetal GP brain using multicomponent driven equilibrium single pulse observation of T1/T2 (mcDESPOT). Regions of interest (ROIs) were placed in the fetal corpus callosum (CC), fornix (FOR), and parasagittal white matter (PSW). Linear regression was performed between five fetal IUGR markers [body volume (BV), body-to-pregnancy volume ratio (BPrVR), brain-to-liver VR (BLVR), brain-to-placenta VR (BPlVR), and brain-to-BVR (BBVR)] and MWF for all regions (coefficient of determination, R2). A t-test with a linear mixed model compared the MWF of non-IUGR and IUGR fetal GPs for all three regions ( = 0.05). The MWF values are as follows: (mean {+/-} standard deviation): 0.23 {+/-} 0.02 (fetal CC), 0.19 {+/-} 0.02 (fetal CC - IUGR), 0.31 {+/-} 0.02 (fetal FOR), 0.27 {+/-} 0.01 (fetal FOR - IUGR), 0.28 {+/-} 0.02 (fetal PSW), and 0.24 {+/-} 0.03 (fetal PSW - IUGR). Significant differences in MWF were found between the non-IUGR and IUGR fetuses in every region. In conclusion, the mean MWF of IUGR fetal GPs is significantly lower than non-IUGR fetal GPs.

biophysics↗

bioRxiv2021

Differential and synergistic effects of low birth weight and Western diet on skeletal muscle vasculature, mitochondrial lipid metabolism and insulin signaling in male guinea pigs

Low birth weight (LBW) offspring are at increased risk for developing insulin resistance, a key precursor in metabolic syndrome and type 2 diabetes mellitus. Altered skeletal muscle vasculature, extracellular matrix, amino acid and mitochondrial lipid metabolism, and insulin signaling are implicated in this pathogenesis. Using uteroplacental insufficiency (UPI) to induce intrauterine growth restriction (IUGR) and LBW in the guinea pig, we investigated the relationship between UPI-induced IUGR/LBW and later life skeletal muscle arteriole density, fibrosis, amino acid and mitochondrial lipid metabolism, markers of insulin signaling and glucose uptake, and how a postnatal high-fat, high-sugar "Western" diet (WD) modulates these changes. Muscle of 145-day-old male LBW glucose tolerant offspring displayed diminished vessel density and altered acylcarnitine levels. Disrupted muscle insulin signaling despite maintained whole-body glucose homeostasis also occurred in both LBW and WD-fed male lean offspring. Additionally, postnatal WD unmasked LBW-induced impairment of mitochondrial lipid metabolism as reflected by increased acylcarnitine accumulation. This study provides evidence that early markers of skeletal muscle metabolic dysfunction appear to be influenced by the in utero environment and interact with a high fat-sugar postnatal environment to exacerbate altered mitochondrial lipid metabolism promoting mitochondrial overload.

physiology↗

bioRxiv2020

Sex-specific Alterations in Hepatic Cholesterol Metabolism in Young Uteroplacental Insufficiency-induced Low Birth Weight Adult Guinea Pig Offspring

BackgroundIntrauterine growth restriction (IUGR) and low birth weight (LBW) have been widely reported as an independent risk factor for hypercholesterolemia and increased hepatic cholesterol underlying liver dysfunction in adulthood. However, the specific impact of uteroplacental insufficiency (UPI), a leading cause of LBW in developed world, on hepatic cholesterol metabolism in later life, is ill defined and is clinically relevant in understanding later life liver metabolic health trajectories. MethodsHepatic cholesterol metabolism pathways were studied in uterine artery ablation-induced LBW and normal birth weight (NBW) male and female guinea pig offspring at postnatal day 150. ResultsHepatic free and total cholesterol were increased in LBW versus NBW males. Transcriptome analysis of LBW versus NBW livers revealed that "Cholesterol metabolism" was an enriched pathway in LBW males but not females. Microsomal triglyceride transfer protein and cytochrome P450 7A1 protein, involved in hepatic cholesterol efflux and catabolism, respectively, and catalase activity were decreased in LBW male livers. Superoxide dismutase activity was reduced in LBW males but increased in LBW females. ConclusionsUPI environment is associated with a later life programed hepatic cholesterol accumulation via impaired cholesterol elimination, in a sex-specific manner. These programmed alterations could underlie later life cholesterol-induced hepatic lipotoxicity in LBW male offspring. Impact StatementO_LILow birth weight (LBW) is a risk factor for adult hypercholesterolemia and increased hepatic cholesterol. C_LIO_LIUteroplacental insufficiency (UPI) resulting in LBW increased hepatic cholesterol content, altered hepatic expression of cholesterol metabolism-related genes in young adult guinea pigs. C_LIO_LIUPI-induced LBW was also associated with markers of a compromised hepatic cholesterol elimination process and failing antioxidant system in young adult guinea pigs. C_LIO_LIThese changes, at the current age studied, were sex-specific, only being observed in LBW males and not LBW females. C_LIO_LIThese programmed alterations could lead to further hepatic damage and greater predisposition to liver diseases in UPI-induced LBW male offspring as they age. C_LI

physiology↗