21 research outputs found
Perinatal Exposure to Bisphenol A Alters Early Adipogenesis in the Rat
BACKGROUND: The causes of the current obesity pandemic have not been fully elucidated. Implication of environmental endocrine disruptors such as bisphenol A (BPA) on adipose tissue development has been poorly investigated. OBJECTIVES: The aim of the present study was to evaluate the effects of perinatal exposure to BPA on early adipose storage at weaning. METHODS: Pregnant Sprague-Dawley rats had access to drinking water containing 1 mg/L BPA from day 6 of gestation through the end of lactation. Pups were weaned on postnatal day (PND) 21. At that time, we investigated perigonadal adipose tissue of pups (weight, histology, gene expression). For the remaining animals, we recorded body weight and food intake for animals on either standard chow or a high-fat diet. RESULTS: Gestational exposure to BPA did not alter the sex ratio or litter size at birth. On PND1, the weight of male and female BPA-exposed pups was increased. On PND21, body weight was increased only in females, in which parametrial white adipose tissue (pWAT) weight was increased about 3-fold. This excess of pWAT was associated with adipocyte hypertrophy and overexpression of lipogenic genes such as C/EBP-alpha (CAAT enhancer binding protein alpha), PPAR-gamma (peroxisome proliferator-activated receptor gamma), SREBP-1C (sterol regulatory element binding protein-1C), LPL (lipoprotein lipase), FAS (fatty acid synthase), and SCD-1 (stearoyl-CoA desaturase 1). In addition, gene expression of SREBP-1C, FAS, and ACC (acetyl-CoA carboxylase) was also increased in liver from BPA-exposed females at PND21, without a change in circulating lipids and glucose. After weaning, perinatal BPA exposure predisposed to overweight in a sex- and diet-dependent manner. We observed no change in food intake due to perinatal BPA exposure in rats on either standard chow or a high-fat diet. CONCLUSIONS: Perinatal exposure to a low dose of BPA increased adipogenesis in females at weaning. Adult body weight may be programmed during early life, leading to changes dependent on the sex and the nutritional status. Although further studies are required to understand the mechanisms of BPA action in early life, these results are particularly important with regard to the increasing prevalence of childhood obesity and the context-dependent action of endocrine disruptors
Activation of nicotinic acetylcholine receptors decreases apoptosis in human and female murine pancreatic islets
Type 1 diabetes (T1DM) results from destruction of most insulin-secreting pancreatic beta-cells. The persistence of beta-cells decades after the onset of the disease indicates that the resistance of individual cells to the autoimmune insult is heterogeneous and might depend on the metabolic status of a cell at a given moment. The aim of this study is to investigate whether activation of nicotinic acetylcholine receptors (nACh-R) could increase beta-cell resistance against the adverse environment prevailing at the onset of T1DM. Here, we show that nACh-R activation by nicotine and choline, two agonists of the receptor, decreases murine and human beta-cell apoptosis induced by pro-inflammatory cytokines known to be present in the islet environment at the onset of T1DM. The protective mechanism activated by nicotine and choline involves attenuation of mitochondrial outer membrane permeabilization via modulation of endoplasmic reticulum stress, of the activity of Bcl-2 family proteins and cytoplasmic calcium levels. Local inflammation and endoplasmic reticulum stress being key determinants of beta-cell death in T1DM, we conclude that pharmacological activation of nACh-R could represent a valuable therapeutic option in the modulation of beta-cell death in T1DM
Mild Neonatal Brain Hypoxia-Ischemia in Very Immature Rats Causes Long-Term Behavioral and Cerebellar Abnormalities at Adulthood
Systemic hypoxia-ischemia (HI) often occurs during preterm birth in human. HI induces injuries to hinder brain cells mainly in the ipsilateral forebrain structures. Such HI injuries may cause lifelong disturbances in the distant regions, such as the contralateral side of the cerebellum. We aimed to evaluate behavior associated with the cerebellum, to acquire cerebellar abundant metabolic alterations using in vivo( 1)H magnetic resonance spectroscopy (H-1 MRS), and to determine GFAP, NeuN, and MBP protein expression in the left cerebellum, in adult rats after mild early postnatal HI on the right forebrain at day 3 (PND3). From PND45, HI animals exhibited increased locomotion in the open field while there is neither asymmetrical forelimb use nor coordination deficits in the motor tasks. Despite the fact that metabolic differences between two cerebellar hemispheres were noticeable, a global increase in glutamine of HI rats was observed and became significant in the left cerebellum compared to the sham-operated group. Furthermore, increases in glutamate, glycine, the sum of glutamate and glutamine and total choline, only occurred in the left cerebellum of HI rats. Remarkably, there were decreased expression of MBP and NeuN but no detectable reactive astrogliosis in the contralateral side of the cerebellum of HI rats. Taken together, the detected alterations observed in the left cerebellum of HI rats may reflect disequilibrium in the glutamate-glutamine cycle and a delay in the return of glutamine from astrocytes to neurons from hypoxic-ischemic origin. Our data provides in vivo evidence of long-term changes in the corresponding cerebellum following mild neonatal HI in very immature rats, supporting the notion that systemic HI could cause cell death in the cerebellum, a distant region from the expected injury site
Concomitant alpha7 and beta2 nicotinic AChR subunit deficiency leads to impaired energy homeostasis and increased physical activity in mice
Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels well characterized in neuronal signal transmission. Moreover, recent studies have revealed nAChR expression in nonneuronal cell types throughout the body, including tissues involved in metabolism. In the present study, we screen gene expression of nAChR subunits in pancreatic islets and adipose tissues. Mice pancreatic islets present predominant expression of α7 and ÎČ2 nAChR subunits but at a lower level than in central structures. Characterization of glucose and energy homeostasis in α7ÎČ2nAChR(-/-) mice revealed no major defect in insulin secretion and sensitivity but decreased glycemia apparently unrelated to gluconeogenesis or glycogenolysis. α7ÎČ2nAChR(-/-) mice presented an increase in lean and bone body mass and a decrease in fat storage with normal body weight. These observations were associated with elevated spontaneous physical activity in α7ÎČ2nAChR(-/-) mice, mainly due to elevation in fine vertical (rearing) activity while their horizontal (ambulatory) activity remained unchanged. In contrast to α7nAChR(-/-) mice presenting glucose intolerance and insulin resistance associated to excessive inflammation of adipose tissue, the present metabolic phenotyping of α7ÎČ2nAChR(-/-) mice revealed a metabolic improvement possibly linked to the increase in spontaneous physical activity related to central ÎČ2nAChR deficiency
Dose-Dependent Neuroprotective Effects of Bovine Lactoferrin Following Neonatal HypoxiaâIschemia in the Immature Rat Brain
Injuries to the developing brain due to hypoxiaâischemia (HI) are common causes of neurological disabilities in preterm babies. HI, with oxygen deprivation to the brain or reduced cerebral blood perfusion due to birth asphyxia, often leads to severe brain damage and sequelae. Injury mechanisms include glutamate excitotoxicity, oxidative stress, bloodâbrain barrier dysfunction, and exacerbated inflammation. Nutritional intervention is emerging as a therapeutic alternative to prevent and rescue brain from HI injury. Lactoferrin (Lf) is an iron-binding protein present in saliva, tears, and breast milk, which has been shown to have antioxidant, anti-inflammatory and anti-apoptotic properties when administered to mothers as a dietary supplement during pregnancy and/or lactation in preclinical studies of developmental brain injuries. However, despite Lfâs promising neuroprotective effects, there is no established dose. Here, we tested three different doses of dietary maternal Lf supplementation using the postnatal day 3 HI model and evaluated the acute neurochemical damage profile using 1H Magnetic Resonance Spectroscopy (MRS) and long-term microstructure alterations using advanced diffusion imaging (DTI/NODDI) allied to protein expression and histological analysis. Pregnant Wistar rats were fed either control diet or bovine Lf supplemented chow at 0.1, 1, or 10 g/kg/body weight concentration from the last day of pregnancy (embryonic day 21âE21) to weaning. At postnatal day 3 (P3), pups from both sexes had their right common carotid artery permanently occluded and were exposed to 6% oxygen for 30 min. Sham rats had the incision but neither surgery nor hypoxia episode. At P4, MRS was performed on a 9.4 T scanner to obtain the neurochemical profile in the cortex. At P4 and P25, histological analysis and protein expression were assessed in the cortex and hippocampus. Brain volumes and ex vivo microstructural analysis using DTI/NODDI parameters were performed at P25. Acute metabolic disturbance induced in cortical tissue by HIP3 was reversed with all three doses of Lf. However, data obtained from MRS show that Lf neuroprotective effects were modulated by the dose. Through western blotting analysis, we observed that HI pups supplemented with Lf at 0.1 and 1 g/kg were able to counteract glutamatergic excitotoxicity and prevent metabolic failure. When 10 g/kg was administered, we observed reduced brain volumes, increased astrogliosis, and hypomyelination, pointing to detrimental effects of high Lf dose. In conclusion, Lf supplementation attenuates, in a dose-dependent manner, the acute and long-term cerebral injury caused by HI. Lf reached its optimal effects at a dose of 1 g/kg, which pinpoints the need to better understand effects of Lf, the pathways involved and possible harmful effects. These new data reinforce our knowledge regarding neuroprotection in developmental brain injury using Lf through lactation and provide new insights into lactoferrinâs neuroprotection capacities and limitation for immature brains
Lactoferrin during lactation protects the immature hypoxic-ischemic rat brain
Lactoferrin (Lf) is an iron-binding glycoprotein secreted in maternal milk presenting anti-inflammatory and antioxidant properties. It shows efficient absorption into the brain from nutritional source. Brain injury frequently resulting from cerebral hypoxia-ischemia (HI) has a high incidence in premature infants with ensuing neurodevelopmental disabilities. We investigated the neuroprotective effect of maternal nutritional supplementation with Lf during lactation in a rat model of preterm HI brain injury using magnetic resonance imaging (MRI), brain gene, and protein expression
Lactoferrin during lactation reduces lipopolysaccharide-induced brain injury
Lactoferrin (Lf), component of maternal milk, has antioxidant, anti-inflammatory and antimicrobial properties. Neuroprotective effects of Lf on the immature brain have been recently shown in rodent models of intrauterine growth restriction and cerebral hypoxia/ischemia. Here we postulated that Lf could also have beneficial effects on preterm inflammatory brain injury. Lf was supplemented in maternal food during lactation and lipopolysaccharide (LPS) was injected in subcortical white matter of rat pups at postnatal day 3 (P3). Effect of maternal Lf supplementation was investigated 24 h (P4), 4 (P7), or 21 days (P24) after LPS injection mainly on the striatum. Lateral ventricle and brain structures volumes were quantified. Microstructure was evaluated by diffusion tensor imaging, neurite orientation dispersion and density imaging as well as electron microscopy. Neurochemical profile was measured by (1) H-magnetic resonance spectroscopy. GFAP protein, proinflammatory cytokines mRNA expression microglial activation were assessed. Lf displayed neuroprotective effects as shown by reduced LPS-induced ventriculomegaly, brain tissue loss, and microstructural modifications, including myelination deficit. (1) H-MRS neurochemical profile was less altered through an antioxidant action of Lf. Despite the lack of effect on LPS-induced proinflammatory cytokines genes expression and on reactive gliosis, microglia was less activated under Lf treatment. In conclusion, Lf supplemented in food during lactation attenuated acute and long-term cerebral LPS-induced alterations. This provides a new evidence for a promising use of Lf as a preventive neuroprotective approach in preterm encephalopathy. © 2016 BioFactors, 42(3):323-336, 2016
Early metabolic defects in dexamethasone-exposed and undernourished intrauterine growth restricted rats.
Poor fetal growth, also known as intrauterine growth restriction (IUGR), is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious "metabolic programming." In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 ”g/kg/day, DEX) or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN). Physiological (glucose and insulin tolerance), morphometric (automated tissue image analysis) and transcriptomic (quantitative PCR) approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming
3D remote sensing as a tool for river and riparian area regional monitoring in Wallonia (Belgium)
Sous lâimpulsion de son administration, la Wallonie a entamĂ© un processus de rĂ©vision des
modalitĂ©s de gestion de ses cours dâeau publics, notamment Ă travers le projet des Programmes
dâactions sur les riviĂšres par une approche intĂ©grĂ©e et sectorisĂ©e (PARIS). Les PARIS ont pour
but dâintĂ©grer dans le temps et dans lâespace lâensemble des mesures de gestion spĂ©cifiques au
linĂ©aire des cours dâeau en fonction dâenjeux prioritaires identifiĂ©s Ă lâĂ©chelle dâunitĂ©s de gestion
homogĂšnes : les secteurs (6 185 secteurs de gestion de 2 km de long en moyenne). La mise
en place et le suivi de ces plans de gestion impliquent de facto le dĂ©veloppement dâoutils de
suivi efficaces, permettant dâĂ©tablir les Ă©tats des lieux pour la planification des actes de gestion
et Ă terme, dâĂ©valuer lâefficacitĂ© desdits plans de gestion. Ces opĂ©rations doivent se rĂ©aliser sur
prĂšs de 12 000 km de cours dâeau et de bandes riveraines associĂ©es sur une base objective
et commune Ă lâensemble des gestionnaires des cours dâeau publics. Des donnĂ©es fines de
tĂ©lĂ©dĂ©tection sont disponibles et acquises de maniĂšre rĂ©guliĂšre par lâadministration wallonne ;
des solutions dérivées de ces sources de données permettront de répondre partiellement aux
besoins réguliers en information des plans de gestion PARIS à un coût réduit.
Pour atteindre cet objectif, un protocole a été établi à partir de nuages de points lidar (light
detection and ranging ; densité 1 point « sol » par m2) complétés par des nuages de points
photogrammétriques. Ces données ont été utilisées afin de caractériser la structure spatiale
des bandes riveraines du réseau hydrographique public wallon à partir de six paramÚtres.
Ces paramĂštres peuvent ĂȘtre dâordre hydromorphologique (hauteur des berges, largeur
et sinuositĂ© du lit mineur), ou dĂ©crire la structure des forĂȘts riveraines (hauteur moyenne et
continuité longitudinale des peuplements arborés et ombrage du lit mineur). Différentes formes
de visualisations de lâinformation peuvent appuyer le processus dĂ©cisionnel des gestionnaires,
de lâĂ©chelle locale (secteurs dâune masse dâeau DCE (directive cadre sur lâeau) Ă lâĂ©chelle
rĂ©gionale (354 masses dâeau DCE). Les paramĂštres extraits dans le cadre de ce projet seront
prochainement intĂ©grĂ©s au sein dâune plateforme informatique permettant leur visualisation Ă
diffĂ©rentes Ă©chelles ainsi que lâencodage des actions par les gestionnaires.The Walloon administration has initiated a process of reform of river management policies, notably
through the project PARIS action programs. The PARIS programs aim the integration in time
and space of all specific management measures regarding public waterways based on priority
issues identified at the level of homogeneous management units (6185 units, with mean length of
2 km). The implementation and monitoring of these management plans involve the development
of effective monitoring tools to establish the initial state, planning acts of management and
evaluating the effectiveness of such management plans. These operations must be carried out
on nearly 12,000 km of streams and associated riparian area. This task must be realized on an
objective and common basis for all of public waterways managers. Fine remote sensing dataâs
are available and regularly acquired by the Walloon administration. Derived solutions of these
data sources will partially meet the information needs of PARIS management plans at reduced
cost.
To achieve this goal, a protocol has been established based on lidar point clouds (density 1 point
«soil»/m2) completed by photogrammetric points clouds. These data were used to characterize
the spatial structure of riparian areas associated with all of the Walloon public water system
(>12,000 km) through six parameters. These parameters can be hydromorphological (height of
banks, width, and sinuosity of the riverbed), or describe the structure of riparian forests (average
height, longitudinal continuity, and shading of the riverbed). Different types of visualizations
can support management decision-making to the local level (single river management unit) to
regional (354 waterbodies of the water framework directive). Through various visualizations at
different scales, the extracted parameters by the project will be integrated into a webGIS platform
used by the river managers to report and plan their management actions