Publications by authors named "Jean Lesage"

56 Publications

Breast milk apelin level increases with maternal obesity and high-fat feeding during lactation.

Int J Obes (Lond) 2021 May 16;45(5):1052-1060. Epub 2021 Feb 16.

Univ. Lille, EA4489 Environnement Périnatal et Santé, Lille, France.

Objective: Recent evidence indicates that levels of breast milk (BM) hormones such as leptin can fluctuate with maternal adiposity, suggesting that BM hormones may signal maternal metabolic and nutritional environments to offspring during postnatal development. The hormone apelin is highly abundant in BM but its regulation during lactation is completely unknown. Here, we evaluated whether maternal obesity and overnutrition impacted BM apelin and leptin levels in clinical cohorts and lactating rats.

Methods: BM and plasma samples were collected from normal-weight and obese breastfeeding women, and from lactating rats fed a control or a high fat (HF) diet during lactation. Apelin and leptin levels were assayed by ELISA. Mammary gland (MG) apelin expression and its cellular localization in lactating rats was measured by quantitative RT-PCR and immunofluorescence, respectively.

Results: BM apelin levels increased with maternal BMI, whereas plasma apelin levels decreased. BM apelin was also positively correlated with maternal insulin and C-peptide levels. In rats, maternal HF feeding exclusively during lactation was sufficient to increase BM apelin levels and decrease its plasma concentration without changing body weight. In contrast, BM leptin levels increased with maternal BMI in humans, but did not change with maternal HF feeding during lactation in rats. Apelin is highly expressed in the rat MG during lactation and was mainly localized to mammary myoepithelial cells. We found that MG apelin gene expression was up-regulated by maternal HF diet and positively correlated with BM apelin content and maternal insulinemia.

Conclusions: Our study indicates that BM apelin levels increase with long- and short-term overnutrition, possibly via maternal hyperinsulinemia and transcriptional upregulation of MG apelin expression in myoepithelial cells. Apelin regulates many physiological processes, including energy metabolism, digestive function, and development. Further studies are needed to unravel the consequences of such changes in offspring development.
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http://dx.doi.org/10.1038/s41366-021-00772-yDOI Listing
May 2021

Identification of new enterosynes using prebiotics: roles of bioactive lipids and mu-opioid receptor signalling in humans and mice.

Gut 2020 Oct 5. Epub 2020 Oct 5.

IRSD, INSERM, Toulouse, Occitanie, France

Objective: The enteric nervous system (ENS) plays a key role in controlling the gut-brain axis under normal and pathological conditions, such as type 2 diabetes. The discovery of intestinal actors, such as enterosynes, able to modulate the ENS-induced duodenal contraction is considered an innovative approach. Among all the intestinal factors, the understanding of the role of gut microbes in controlling glycaemia is still developed. We studied whether the modulation of gut microbiota by prebiotics could permit the identification of novel enterosynes.

Design: We measured the effects of prebiotics on the production of bioactive lipids in the intestine and tested the identified lipid on ENS-induced contraction and glucose metabolism. Then, we studied the signalling pathways involved and compared the results obtained in mice to human.

Results: We found that modulating the gut microbiota with prebiotics modifies the actions of enteric neurons, thereby controlling duodenal contraction and subsequently attenuating hyperglycaemia in diabetic mice. We discovered that the signalling pathway involved in these effects depends on the synthesis of a bioactive lipid 12-hydroxyeicosatetraenoic acid (12-HETE) and the presence of mu-opioid receptors (MOR) on enteric neurons. Using pharmacological approaches, we demonstrated the key role of the MOR receptors and proliferator-activated receptor γ for the effects of 12-HETE. These findings are supported by human data showing a decreased expression of the proenkephalin and MOR messanger RNAs in the duodenum of patients with diabetic.

Conclusions: Using a prebiotic approach, we identified enkephalin and 12-HETE as new enterosynes with potential real beneficial and safety impact in diabetic human.
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http://dx.doi.org/10.1136/gutjnl-2019-320230DOI Listing
October 2020

Epigenetics: Linking Early Postnatal Nutrition to Obesity Programming?

Nutrients 2019 Dec 5;11(12). Epub 2019 Dec 5.

University Lille, EA4489 Environnement Périnatal et Santé, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F-59000 Lille, France.

Despite constant research and public policy efforts, the obesity epidemic continues to be a major public health threat, and new approaches are urgently needed. It has been shown that nutrient imbalance in early life, from conception to infancy, influences later obesity risk, suggesting that obesity could result from "developmental programming". In this review, we evaluate the possibility that early postnatal nutrition programs obesity risk via epigenetic mechanisms, especially DNA methylation, focusing on four main topics: (1) the dynamics of epigenetic processes in key metabolic organs during the early postnatal period; (2) the epigenetic effects of alterations in early postnatal nutrition in animal models or breastfeeding in humans; (3) current limitations and remaining outstanding questions in the field of epigenetic programming; (4) candidate pathways by which early postnatal nutrition could epigenetically program adult body weight set point. A particular focus will be given to the potential roles of breast milk fatty acids, neonatal metabolic and hormonal milieu, and gut microbiota. Understanding the mechanisms by which early postnatal nutrition can promote lifelong metabolic modifications is essential to design adequate recommendations and interventions to "de-program" the obesity epidemic.
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http://dx.doi.org/10.3390/nu11122966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950532PMC
December 2019

Transcription profiling in the liver of undernourished male rat offspring reveals altered lipid metabolism pathways and predisposition to hepatic steatosis.

Am J Physiol Endocrinol Metab 2019 12 22;317(6):E1094-E1107. Epub 2019 Oct 22.

Université Lille, EA4489, Equipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, Lille, France.

Clinical and animal studies have reported an association between low birth weight and the development of nonalcoholic fatty liver disease (NAFLD) in offspring. Using a model of prenatal maternal 70% food restriction diet (FR30) in the rat, we previously showed that maternal undernutrition predisposes offspring to altered lipid metabolism in adipose tissue, especially on a high-fat (HF) diet. Here, using microarray-based expression profiling combined with metabolic, endocrine, biochemical, histological, and lipidomic approaches, we assessed whether FR30 procedure sensitizes adult male offspring to impaired lipid metabolism in the liver. No obvious differences were noted in the concentrations of triglycerides, cholesterol, and bile acids in the liver of 4-mo-old FR30 rats whichever postweaning diet was used. However, several clues suggest that offspring's lipid metabolism and steatosis are modified by maternal undernutrition. First, lipid composition was changed (i.e., higher total saturated fatty acids and lower elaidic acid) in the liver, whereas larger triglyceride droplets were observed in hepatocytes of undernourished rats. Second, FR30 offspring exhibited longterm impact on hepatic gene expression and lipid metabolism pathways on a chow diet. Although the transcriptome profile was globally modified by maternal undernutrition, cholesterol and bile acid biosynthesis pathways appear to be key targets, indicating that FR30 animals were predisposed to impaired hepatic cholesterol metabolism. Third, the FR30 protocol markedly modifies hepatic gene transcription profiles in undernourished offspring in response to postweaning HF. Overall, FR30 offspring may exhibit impaired metabolic flexibility, which does not enable them to properly cope with postweaning nutritional challenges influencing the development of nonalcoholic fatty liver.
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http://dx.doi.org/10.1152/ajpendo.00291.2019DOI Listing
December 2019

Elabela and Apelin actions in healthy and pathological pregnancies.

Cytokine Growth Factor Rev 2019 04 16;46:45-53. Epub 2019 Mar 16.

Univ. Lille, EA4489 Environnement Périnatal et Santé, F-59000 Lille, France. Electronic address:

Pregnancy is a dynamic and precisely organized process during which one or more baby develops. Embryonic development relies on the formation of the placenta, allowing nutrient and oxygen exchange between the mother and the fetus. Dysfunction of placental formation lead to pregnancy disorders such as preeclampsia (PE) with serious deleterious consequences for fetal and maternal health. Identifying factors involved in fetoplacental homeostasis could inform better diagnostic and therapeutic strategies for these pathological pregnancies. Here, we summarize actions of elabela, apelin and their common receptor APJ in the fetoplacental unit. Studies indicate that elabela is crucial for embryo cardiovascular system formation and early placental development, while apelin acts in mid/late gestation to modulate fetal angiogenesis and energy homeostasis. Most of these findings, drawn from animal models, indicate a key role of elabela/apelin-APJ system in the fetoplacental unit. This review also provides an overview of clinical studies investigating elabela/apelin-APJ system in pathological complicated pregnancies such as PE and gestational diabetes mellitus (GDM). While elabela-deficient mice display all the features of PE, current clinical studies show no difference in circulating elabela levels between PE and control patients which does not support a role in PE development. Conversely, apelin levels are increased during PE, but the use of apelin as an early PE marker remains to be fully investigated.
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http://dx.doi.org/10.1016/j.cytogfr.2019.03.003DOI Listing
April 2019

Maternal high-fat diet during suckling programs visceral adiposity and epigenetic regulation of adipose tissue stearoyl-CoA desaturase-1 in offspring.

Int J Obes (Lond) 2019 12 8;43(12):2381-2393. Epub 2019 Jan 8.

Univ. Lille, EA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F-59000, Lille, France.

Objective: The lactation-suckling period is critical for white adipose tissue (WAT) development. Early postnatal nutrition influences later obesity risk but underlying mechanisms remain elusive. Here, we tested whether altered postnatal nutrition specifically during suckling impacts epigenetic regulation of key metabolic genes in WAT and alter long-term adiposity set point.

Methods: We analyzed the effects of maternal high-fat (HF) feeding in rats exclusively during lactation-suckling on breast milk composition and its impact on male offspring visceral epidydimal (eWAT) and subcutaneous inguinal (iWAT) depots during suckling and in adulthood.

Results: Maternal HF feeding during lactation had no effect on mothers' body weight (BW) or global breast milk composition, but induced qualitative changes in breast milk fatty acid (FA) composition (high n-6/n-3 polyunsaturated FA ratio and low medium-chain FA content). During suckling, HF neonates showed increased BW and mass of both eWAT and iWAT depot but only eWAT displayed an enhanced adipogenic transcriptional signature. In adulthood, HF offspring were predisposed to weight gain and showed increased hyperplastic growth only in eWAT. This specific eWAT expansion was associated with increased expression and activity of stearoyl-CoA desaturase-1 (SCD1), a key enzyme of FA metabolism. SCD1 converts saturated FAs, e.g. palmitate and stearate, to monounsaturated FAs, palmitoleate and oleate, which are the predominant substrates for triglyceride synthesis. Scd1 upregulation in eWAT was associated with reduced DNA methylation in Scd1 promoter surrounding a PPARγ-binding region. Conversely, changes in SCD1 levels and methylation were not observed in iWAT, coherent with a depot-specific programming.

Conclusions: Our data reveal that maternal HF feeding during suckling programs long-term eWAT expansion in part by SCD1 epigenetic reprogramming. This programming events occurred with drastic changes in breast milk FA composition, suggesting that dietary FAs are key metabolic programming factors in the early postnatal period.
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http://dx.doi.org/10.1038/s41366-018-0310-zDOI Listing
December 2019

Food-Derived Hemorphins Cross Intestinal and Blood-Brain Barriers .

Front Endocrinol (Lausanne) 2018 10;9:159. Epub 2018 Apr 10.

Université de Lille INRA, ISA, Université d'Artois, Université Littoral Côte d'Opale, EA 7394-ICV Institut Charles Viollette, Lille, France.

A qualitative study is presented, where the main question was whether food-derived hemorphins, i.e., originating from digested alimentary hemoglobin, could pass the intestinal barrier and/or the blood-brain barrier (BBB). Once absorbed, hemorphins are opioid receptor (OR) ligands that may interact with peripheral and central OR and have effects on food intake and energy balance regulation. LLVV-YPWT (LLVV-H4), LVV-H4, VV-H4, VV-YPWTQRF (VV-H7), and VV-H7 hemorphins that were previously identified in the 120 min digest resulting from the simulated gastrointestinal digestion of hemoglobin have been synthesized to be tested in models of passage of IB and BBB. LC-MS/MS analyses yielded that all hemorphins, except the LLVV-H4 sequence, were able to cross intact the human intestinal epithelium model with Caco-2 cells within 5-60 min when applied at 5 mM. Moreover, all hemorphins crossed intact the human BBB model with brain-like endothelial cells (BLEC) within 30 min when applied at 100 µM. Fragments of these hemorphins were also detected, especially the YPWT common tetrapeptide that retains OR-binding capacity. A cAMP assay performed in Caco-2 cells indicates that tested hemorphins behave as OR agonists in these cells by reducing cAMP production. We further provide preliminary results regarding the effects of hemorphins on tight junction proteins, specifically here the claudin-4 that is involved in paracellular permeability. All hemorphins at 100 µM, except the LLVV-H4 peptide, significantly decreased claudin-4 mRNA levels in the Caco-2 intestinal model. This study is a first step toward demonstrating food-derived hemorphins bioavailability which is in line with the growing body of evidence supporting physiological functions for food-derived peptides.
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http://dx.doi.org/10.3389/fendo.2018.00159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903475PMC
April 2018

Reduced PPARγ2 expression in adipose tissue of male rat offspring from obese dams is associated with epigenetic modifications.

FASEB J 2018 05 8;32(5):2768-2778. Epub 2018 Jan 8.

Equipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, Equipe d'Accueil (EA) 4489, University of Lille, Lille, France.

According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and accelerated growth in neonates program obesity later in life. White adipose tissue (WAT) has been the focus of developmental programming events, although underlying mechanisms remain elusive. In rodents, WAT development primarily occurs during lactation. We previously reported that adult rat offspring from dams fed a high-fat (HF) diet exhibited fat accumulation and decreased peroxisome proliferator-activated receptor γ (PPARγ) mRNA levels in WAT. We hypothesized that PPARγ down-regulation occurs via epigenetic malprogramming which takes place during adipogenesis. We therefore examined epigenetic modifications in the PPARγ1 and PPARγ2 promoters in perirenal (pWAT) and inguinal fat pads of HF offspring at weaning (postnatal d 21) and in adulthood. Postnatal d 21 is a period characterized by active epigenomic remodeling in the PPARγ2 promoter (DNA hypermethylation and depletion in active histone modification H3ac and H3K4me3) in pWAT, consistent with increased DNA methyltransferase and DNA methylation activities. Adult HF offspring exhibited sustained hypermethylation and histone modification H3ac of the PPARγ2 promoter in both deposits, correlated with persistent decreased PPARγ2 mRNA levels. Consistent with the DOHaD hypothesis, retained epigenetic marks provide a mechanistic basis for the cellular memory linking maternal obesity to a predisposition for later adiposity.-Lecoutre, S., Pourpe, C., Butruille, L., Marousez, L., Laborie, C., Guinez, C., Lesage, J., Vieau, D., Eeckhoute, J., Gabory, A., Oger, F., Eberlé, D., Breton, C. Reduced PPARγ2 expression in adipose tissue of male rat offspring from obese dams is associated with epigenetic modifications.
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http://dx.doi.org/10.1096/fj.201700997RDOI Listing
May 2018

Maternal obesity programs increased leptin gene expression in rat male offspring via epigenetic modifications in a depot-specific manner.

Mol Metab 2017 08 31;6(8):922-930. Epub 2017 May 31.

Univ. Lille, EA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F-59000 Lille, France. Electronic address:

Objective: According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and accelerated growth in neonates predispose offspring to white adipose tissue (WAT) accumulation. In rodents, adipogenesis mainly develops during lactation. The mechanisms underlying the phenomenon known as developmental programming remain elusive. We previously reported that adult rat offspring from high-fat diet-fed dams (called HF) exhibited hypertrophic adipocyte, hyperleptinemia and increased leptin mRNA levels in a depot-specific manner. We hypothesized that leptin upregulation occurs via epigenetic malprogramming, which takes place early during development of WAT.

Methods: As a first step, we identified two potential enhancers located upstream and downstream of the leptin transcription start site that exhibit strong dynamic epigenomic remodeling during adipocyte differentiation. We then focused on epigenetic modifications (methylation, hydroxymethylation, and histone modifications) of the promoter and the two potential enhancers regulating leptin gene expression in perirenal (pWAT) and inguinal (iWAT) fat pads of HF offspring during lactation (postnatal days 12 (PND12) and 21 (PND21)) and in adulthood.

Results: PND12 is an active period for epigenomic remodeling in both deposits especially in the upstream enhancer, consistent with leptin gene induction during adipogenesis. Unlike iWAT, some of these epigenetic marks were still observable in pWAT of weaned HF offspring. Retained marks were only visible in pWAT of 9-month-old HF rats that showed a persistent "expandable" phenotype.

Conclusions: Consistent with the DOHaD hypothesis, persistent epigenetic remodeling occurs at regulatory regions especially within intergenic sequences, linked to higher leptin gene expression in adult HF offspring in a depot-specific manner.
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http://dx.doi.org/10.1016/j.molmet.2017.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518658PMC
August 2017

Simulated GI digestion of dietary protein: Release of new bioactive peptides involved in gut hormone secretion.

Food Res Int 2016 Nov 27;89(Pt 1):382-390. Epub 2016 Aug 27.

Univ. Lille, EA 7394- ICV - Institut Charles Viollette, F-59000 Lille, France.

Dietary proteins have been reported to induce a strong feeling of satiety that has been partially explained by gut hormone level increase. Up to date, various protein hydrolysates have demonstrated in vitro and in vivo their potential to stimulate gut hormone secretion related to food intake decrease and their mechanisms of action have just started to be resolved. In this context, this study aimed at identifying new peptide sequences involved in gut hormone secretion released by protein in vitro gastrointestinal digestion. Targeted gut hormones were Cholecystokinin (CCK) and Glucagon-Like Peptide 1 (GLP-1). The activity of DPP-IV was also considered as it strongly modulates GLP-1 action. In a previous study, simulated digestion of dietary protein has generated hydrolysates with enhancing effect on CCK and GLP-1 secretion in STC-1 cells as well as DPP-IV inhibitory properties. Successive purification steps were performed to isolate peptide fractions involved in these bioactivities whose sequence was determined by LC-MS-MS. Three peptide sequences ANVST, TKAVEH and KAAVT were pointed out for their stimulating effects on GLP-1 secretion. The sequence VAAA was isolated for its DPP-IV inhibitory properties. Two peptide groups were strongly involved in CCK release sharing a certain occurrence of aromatic amino acid residues.
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http://dx.doi.org/10.1016/j.foodres.2016.08.033DOI Listing
November 2016

Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice.

Sci Rep 2016 08 23;6:31849. Epub 2016 Aug 23.

Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.

Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions. We have shown that chronic icv infusion of apelin increases the expression of pro-inflammatory factors in the hypothalamus associated with an increase in plasma interleukin-1 beta. In parallel, mice infused with icv apelin exhibit a significant lower energy expenditure coupled to a decrease in PGC1alpha, PRDM16 and UCP1 expression in brown adipose tissue which could explain the alteration of thermogenesis in these mice. These data provide compelling evidence that central apelin contributes to the development of type 2 diabetes by altering energy expenditure, thermogenesis and fat browning.
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http://dx.doi.org/10.1038/srep31849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994119PMC
August 2016

Depot- and sex-specific effects of maternal obesity in offspring's adipose tissue.

J Endocrinol 2016 07 27;230(1):39-53. Epub 2016 Apr 27.

Univ. LilleEA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F59000 Lille, France

According to the Developmental Origin of Health and Disease (DOHaD) concept, alterations of nutrient supply in the fetus or neonate result in long-term programming of individual body weight (BW) setpoint. In particular, maternal obesity, excessive nutrition, and accelerated growth in neonates have been shown to sensitize offspring to obesity. The white adipose tissue may represent a prime target of metabolic programming induced by maternal obesity. In order to unravel the underlying mechanisms, we have developed a rat model of maternal obesity using a high-fat (HF) diet (containing 60% lipids) before and during gestation and lactation. At birth, newborns from obese dams (called HF) were normotrophs. However, HF neonates exhibited a rapid weight gain during lactation, a key period of adipose tissue development in rodents. In males, increased BW at weaning (+30%) persists until 3months of age. Nine-month-old HF male offspring was normoglycemic but showed mild glucose intolerance, hyperinsulinemia, and hypercorticosteronemia. Despite no difference in BW and energy intake, HF adult male offspring was predisposed to fat accumulation showing increased visceral (gonadal and perirenal) depots weights and hyperleptinemia. However, only perirenal adipose tissue depot exhibited marked adipocyte hypertrophy and hyperplasia with elevated lipogenic (i.e. sterol-regulated element binding protein 1 (Srebp1), fatty acid synthase (Fas), and leptin) and diminished adipogenic (i.e. peroxisome proliferator-activated receptor gamma (Pparγ), 11β-hydroxysteroid dehydrogenase type 1 (11β-Hds1)) mRNA levels. By contrast, very few metabolic variations were observed in HF female offspring. Thus, maternal obesity and accelerated growth during lactation program offspring for higher adiposity via transcriptional alterations of visceral adipose tissue in a depot- and sex-specific manner.
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http://dx.doi.org/10.1530/JOE-16-0037DOI Listing
July 2016

Maternal obesity alters the apelinergic system at the feto-maternal interface.

Placenta 2016 Mar 12;39:41-4. Epub 2016 Jan 12.

University of Lille 1, EA 4489, Villeneuve d'Ascq, France. Electronic address:

Apelin and its receptor APJ have been implicated in pathologies including cardiovascular disease, diabetes and obesity. Little is known about the function of the apelinergic system during gestation. We evaluated in mice this system at the feto-maternal interface in insulin-resistant obese female (HF) mice. Maternal apelinemia was decreased at term and fetal apelinemia was sixfold higher than maternal level. Ex-vivo, the placenta releases apelin at E12.5 and E18.5. In HF pregnant mice at term, apelinemia as well as placental apelin and APJ mRNA levels were increased whereas placental release of apelin was drastically reduced compared to controls.
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http://dx.doi.org/10.1016/j.placenta.2016.01.006DOI Listing
March 2016

[Maternal nutritional manipulations: is the adipose tissue a key target of programming?].

Med Sci (Paris) 2016 Jan 5;32(1):81-4. Epub 2016 Feb 5.

UPRES EA 4489, Environnement Périnatal et Santé, équipe malnutrition maternelle et programmation des maladies métaboliques, Université de Lille, 59650 Villeneuve d'Ascq, France.

The nutritional imprinting, whose mechanisms remain still dark and which seem to continue through the following generations, highlight the key-role of the inadequacy between the pre-and postnatal nutritional environment and the programming of the obesity.
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http://dx.doi.org/10.1051/medsci/20163201013DOI Listing
January 2016

Apelin Controls Fetal and Neonatal Glucose Homeostasis and Is Altered by Maternal Undernutrition.

Diabetes 2016 Mar 2;65(3):554-60. Epub 2015 Dec 2.

Unité Environnement Périnatal et Santé, Equipe d'accueil 4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, Université de Lille, Villeneuve d'Ascq, France

The adequate control of glucose homeostasis during both gestation and early postnatal life is crucial for the development of the fetoplacental unit and adaptive physiological responses at birth. Growing evidences indicate that apelin and its receptor, APJ, which are expressed across a wide range of tissues, exert important roles in glucose homeostasis in adults. However, little is known about the function of the apelinergic system during gestation. In this study, we evaluated the activity of this system in rats, the role of apelin in fetal and neonatal glucose homeostasis, and its modulation by maternal food restriction. We found that 1) the apelinergic system was expressed at the fetoplacental interface and in numerous fetal tissues, 2) ex vivo, the placenta released high amounts of apelin in late gestation, 3) intravenous apelin injection in mothers increased the transplacental transport of glucose, and 4) intraperitoneal apelin administration in neonates increased glucose uptake in lung and muscle. Maternal food restriction drastically reduced apelinemia in both mothers and growth-restricted fetuses and altered the expression of the apelinergic system at the fetoplacental interface. Together, our data demonstrate that apelin controls fetal and neonatal glucose homeostasis and is altered by fetal growth restriction induced by maternal undernutrition.
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http://dx.doi.org/10.2337/db15-0228DOI Listing
March 2016

Epidermal TRPM8 channel isoform controls the balance between keratinocyte proliferation and differentiation in a cold-dependent manner.

Proc Natl Acad Sci U S A 2015 Jun 15;112(26):E3345-54. Epub 2015 Jun 15.

Inserm U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer et LABEX (Laboratoire d'excellence), Université Lille1, 59655 Villeneuve d'Ascq, France;

Deviation of the ambient temperature is one of the most ubiquitous stimuli that continuously affect mammals' skin. Although the role of the warmth receptors in epidermal homeostasis (EH) was elucidated in recent years, the mystery of the keratinocyte mild-cold sensor remains unsolved. Here we report the cloning and characterization of a new functional epidermal isoform of the transient receptor potential M8 (TRPM8) mild-cold receptor, dubbed epidermal TRPM8 (eTRPM8), which is localized in the keratinocyte endoplasmic reticulum membrane and controls mitochondrial Ca(2+) concentration ([Ca(2+)]m). In turn, [Ca(2+)]m modulates ATP and superoxide (O2(·-)) synthesis in a cold-dependent manner. We report that this fine tuning of ATP and O2(·-) levels by cooling controls the balance between keratinocyte proliferation and differentiation. Finally, to ascertain eTRPM8's role in EH in vivo we developed a new functional knockout mouse strain by deleting the pore domain of TRPM8 and demonstrated that eTRPM8 knockout impairs adaptation of the epidermis to low temperatures.
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http://dx.doi.org/10.1073/pnas.1423357112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491737PMC
June 2015

[Discovery of Toddler/Elabela ligand and the double life of the apelin receptor].

Med Sci (Paris) 2015 May 9;31(5):481-3. Epub 2015 Jun 9.

Unité environnement périnatal et santé, EA4489, Université de Lille 1, bâtiment SN4, 59655 Villeneuve d'Ascq, France.

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http://dx.doi.org/10.1051/medsci/20153105007DOI Listing
May 2015

Photodynamic therapy of ovarian cancer peritoneal metastasis with hexaminolevulinate: a toxicity study.

Photodiagnosis Photodyn Ther 2014 Sep 28;11(3):265-74. Epub 2014 Apr 28.

INSERM U703, Univ Lille Nord de France, Lille University Hospital, Lille, France; GDR 3049 Médicaments Photoactivables - Photochimiothérapie (PHOTOMED), France. Electronic address:

Context: While photodynamic therapy (PDT) is a promising treatment for peritoneal carcinomatosis, its use is often limited because of the toxicity of photosensitizers. In this study, safety of PDT with hexaminoevulinate (HAL), a second generation photosensitizer, is assessed.

Methods: PDT of the peritoneal cavity was performed in a rat model of peritoneal carcinomatosis. Rats were treated according to different protocols: with full or half HAL dose, after intraperitoneal or oral administration of HAL, 4 or 8h after its injection, using red or green light, after protection of the liver or cooling of the abdominal wall. Toxicity was assessed by blood tests quantifying hematocrit, liver and muscular enzymes and by pathological examination of abdominal and intrathoracic organs after treatment. The results were analyzed in the light of quantification of fluorescence and protoporphyrin IX (PPIX) content of the same organs.

Results: PDT with HAL induced rhabdomyolysis, intestinal necrosis and liver function test anomalies, leading to death in 2 out of 34 rats. The liver and the intestine contained high levels of PPIX (3-5 times more than tumor nodules).

Conclusion: HAL PDT lacked specificity. However, the strategy associating diagnosis, treatment and evaluation of the results in one single procedure was effective and should be tested with other photosensitizers.
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http://dx.doi.org/10.1016/j.pdpdt.2014.04.006DOI Listing
September 2014

Apelin stimulates both cholecystokinin and glucagon-like peptide 1 secretions in vitro and in vivo in rodents.

Peptides 2013 Oct 14;48:134-6. Epub 2013 Aug 14.

Univ Lille Nord de France, Unité Environnement Périnatal et Croissance, EA 4489, Equipe dénutritions maternelles périnatales, Université de Lille 1, Bâtiment SN4, 59655 Villeneuve d'Ascq, France.

Apelin is an enteric peptide that exerts several digestive functions such as stimulation of cell proliferation and cholecystokinin (CCK) secretion. We investigated using murine enteroendocrine cell line (STC-1) and rats if apelin-13 stimulates both CCK and glucagon-like peptide 1 (GLP-1) secretions. We demonstrated that, in vitro and in vivo, apelin-13 increases the release of these two hormones in a dose-dependent manner. Present data suggest that apelin may modulate digestive functions, food intake behavior and glucose homoeostasis via apelin-induced release of enteric CCK but also through a new incretin-releasing activity on enteric GLP-1.
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http://dx.doi.org/10.1016/j.peptides.2013.08.005DOI Listing
October 2013

Hypothalamic apelin/reactive oxygen species signaling controls hepatic glucose metabolism in the onset of diabetes.

Antioxid Redox Signal 2014 Feb 18;20(4):557-73. Epub 2013 Sep 18.

1 Institut National de la Santé et de la Recherche Médicale (INSERM) , Toulouse, France .

Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver glucose metabolism and glycemia.

Results: We show that icv apelin injection stimulates liver glycogenolysis and gluconeogenesis via an over-activation of the sympathetic nervous system (SNS), leading to fasted hyperglycemia. The effect of central apelin on liver function is dependent of an increased production of hypothalamic reactive oxygen species (ROS). These data are strengthened by experiments using lentiviral vector-mediated over-expression of apelin in hypothalamus of mice that present over-activation of SNS associated to an increase in hepatic glucose production. Finally, we report that mice fed a high-fat diet present major alterations of hypothalamic apelin/ROS signaling, leading to activation of glycogenolysis. INNOVATION/CONCLUSION: These data bring compelling evidence that hypothalamic apelin is one master switch that participates in the onset of diabetes by directly acting on liver function. Our data support the idea that hypothalamic apelin is a new potential therapeutic target to treat diabetes.
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http://dx.doi.org/10.1089/ars.2013.5182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901354PMC
February 2014

New design of textile light diffusers for photodynamic therapy.

Mater Sci Eng C Mater Biol Appl 2013 Apr 8;33(3):1170-5. Epub 2012 Dec 8.

Univ Lille Nord de France, F-59000 Lille, France.

A homogeneous and reproducible fluence delivery rate during clinical photodynamic therapy (PDT) plays a determinant role in preventing under- or overtreatment. PDT applied in dermatology has been carried out with a wide variety of light sources delivering a broad range of more or less adapted light doses. Due to the complexities of the human anatomy, these light sources do not in fact deliver a uniform light distribution to the skin. Therefore, the development of flexible light sources would considerably improve the homogeneity of light delivery. The integration of plastic optical fiber (POF) into textile structures could offer an interesting alternative. In this article, a textile light diffuser (TLD) has been developed using POF and Polyester yarns. Predetermined POF macrobending leads to side emission of light when the critical angle is exceeded. Therefore, a specific pattern based on different satin weaves has been developed in order to improve light emission homogeneity and to correct the decrease of side emitted radiation intensity along POF. The prototyped fabrics (approximately 100 cm(2): 5×20 cm) were woven using a hand loom, then both ends of the POF were coupled to a laser diode (5 W, 635 nm). The fluence rate (mW/ cm(2)) and the homogeneity of light delivery by the TLD were evaluated. Temperature evolution, as a function of time, was controlled with an infrared thermographic camera. When using a power source of 5 W, the fluence rate of the TLD was 18±2.5 mw/cm(2). Due to the high efficiency of the TLD, the optical losses were very low. The TLD temperature elevation was 0.6 °C after 10 min of illumination. Our TLD meets the basic requirements for PDT: homogeneous light distribution and flexibility. It also proves that large (500 cm(2)) textile light diffusers adapted to skin, but also to peritoneal or pleural cavity, PDTs can be easily produced by textile manufacturing processes.
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http://dx.doi.org/10.1016/j.msec.2012.12.007DOI Listing
April 2013

The apelinergic system: sexual dimorphism and tissue-specific modulations by obesity and insulin resistance in female mice.

Peptides 2013 Aug 5;46:94-101. Epub 2013 Jun 5.

Unité Environnement Périnatal et Croissance, EA 4489, Faculté de Médecine, Université Lille Nord de France, Pôle Recherche, IFR 114, 59045 Lille, France.

It has been proposed that the apelinergic system (apelin and its receptor APJ) may be a promising therapeutic target in obesity-associated insulin resistance syndrome. However, due to the extended tissue-distribution of this system, the therapeutic use of specific ligands for APJ may target numerous tissues resulting putatively to collateral deleterious effects. To unravel specific tissular dysfunctions of this system under obesity and insulin-resistance conditions, we measured the apelinemia and gene-expression level of both apelin (APL) and APJ in 12-selected tissues of insulin-resistant obese female mice fed with a high fat (HF) diet. In a preliminary study, we compared between adult male and female mice, the circadian plasma apelin variation and the effect of fasting on apelinemia. No significant differences were found for these parameters suggesting that the apelinemia is not affected by the sex. Moreover, plasma apelin level was not modulated during the four days of the estrous cycle in females. In obese and insulin-resistant HF female mice, plasma apelin concentration after fasting was not modified but, the gene-expression level of the APL/APJ system was augmented in the white adipose tissue (WAT) and reduced in the brown adipose tissue (BAT), the liver and in kidneys. BAT apelin content was reduced in HF female mice. Our data suggest that the apelinergic system may be implicated into specific dysfunctions of these tissues under obesity and diabetes and that, pharmacologic modulations of this system may be of interest particularly in the treatment of adipose, liver and renal dysfunctions that occur during these pathologies.
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http://dx.doi.org/10.1016/j.peptides.2013.05.013DOI Listing
August 2013

The hypothalamic POMC mRNA expression is upregulated in prenatally undernourished male rat offspring under high-fat diet.

Peptides 2013 May 20;43:146-54. Epub 2013 Mar 20.

Unité Environnement Périnatal et Croissance, UPRES EA 4489, Equipe Dénutritions Maternelles Périnatales, Université Lille-Nord de France, Villeneuve d'Ascq, France.

Epidemiological studies demonstrated that adverse environmental factors leading to intrauterine growth retardation (IUGR) and low birth weight may predispose individuals to increased risk of metabolic syndrome. In rats, we previously demonstrated that adult male IUGR offspring from prenatal 70% food-restricted dams throughout gestation (FR30) were predisposed to energy balance dysfunctions such as impaired glucose intolerance, hyperleptinemia, hyperphagia and adiposity. We investigated whether postweaning moderate high-fat (HF) diet would amplify the phenotype focusing on the hypothalamus gene expression profile. Prenatally undernourished rat offspring were HF-fed from weaning until adulthood while body weight and food intake were measured. Tissue weights, glucose tolerance and plasma endocrine parameters levels were determined in 4-month-old rats. Hypothalamic gene expression profiling of adult FR30 rat was performed using Illumina microarray analysis and the RatRef-12 Expression BeadChip that contains 21,792 rat genes. Under HF diet, contrary to C animals, FR30 rats displayed increased body weight. However, most of the endocrine disorders observed in chow diet-fed adult FR30 were alleviated. We also observed very few gene expression changes in hypothalamus of FR30 rat. Amongst factors involved in hypothalamic energy homeostasis programming system, only the POMC and transthyretin mRNA expression levels were preferentially increased under HF diet. Both elevated gene expression levels may be seen as adaptive mechanisms counteracting against deleterious effects of HF feeding in FR30 animals. This study shows that the POMC gene expression is a key target of long-term developmental programming in prenatally undernourished male rat offspring, specifically within an obesogenic environment.
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http://dx.doi.org/10.1016/j.peptides.2013.03.013DOI Listing
May 2013

Maternal diets trigger sex-specific divergent trajectories of gene expression and epigenetic systems in mouse placenta.

PLoS One 2012 5;7(11):e47986. Epub 2012 Nov 5.

INRA, UMR1198 Biologie du Développement et Reproduction, Jouy-en-Josas, France.

Males and females responses to gestational overnutrition set the stage for subsequent sex-specific differences in adult onset non communicable diseases. Placenta, as a widely recognized programming agent, contibutes to the underlying processes. According to our previous findings, a high-fat diet during gestation triggers sex-specific epigenetic alterations within CpG and throughout the genome, together with the deregulation of clusters of imprinted genes. We further investigated the impact of diet and sex on placental histology, transcriptomic and epigenetic signatures in mice. Both basal gene expression and response to maternal high-fat diet were sexually dimorphic in whole placentas. Numerous genes showed sexually dimorphic expression, but only 11 genes regardless of the diet. In line with the key role of genes belonging to the sex chromosomes, 3 of these genes were Y-specific and 3 were X-specific. Amongst all the genes that were differentially expressed under a high-fat diet, only 16 genes were consistently affected in both males and females. The differences were not only quantitative but remarkably qualitative. The biological functions and networks of genes dysregulated differed markedly between the sexes. Seven genes of the epigenetic machinery were dysregulated, due to effects of diet, sex or both, including the Y- and X-linked histone demethylase paralogues Kdm5c and Kdm5d, which could mark differently male and female epigenomes. The DNA methyltransferase cofactor Dnmt3l gene expression was affected, reminiscent of our previous observation of changes in global DNA methylation. Overall, this striking sexual dimorphism of programming trajectories impose a considerable revision of the current dietary interventions protocols.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0047986PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489896PMC
April 2013

Maternal hypertension induced by NO blockade does not program adult metabolic diseases in growth-restricted rat fetuses.

Metabolism 2013 Mar 30;62(3):442-5. Epub 2012 Oct 30.

Université Lille Nord de France, Unité Environnement Périnatal et Croissance, EA 4489, Faculté de Médecine, Pôle Recherche, IFR 114, 59045 Lille.

Objective: Preeclampsia is a frequent and potentially lethal placental insufficiency pathology causing maternal hypertension and proteinuria, as well as a high rate of intrauterine growth retardation (IUGR) in offspring. Reduced nitric oxide (NO) production may play a role in the mechanisms of this disease. As exposure to adverse early life environment and IUGR has been proposed to increase cardiometabolic diseases risk, we investigated in rats the effects of maternal NO blockade on growth and metabolic phenotype of offspring.

Material And Methods: Osmotic pumps were implanted in pregnant rats at E17 and diffused saline or L-NAME (50mg/day), a nitric oxide synthesis inhibitor. At birth, IUGR male newborns without limb defects were selected. Body growth, feeding behavior and glucose tolerance were evaluated in offspring. Organs weights, plasma level of several metabolic hormones and genes expressions were determined in fasted 9month-old rats.

Results: L-NAME mothers had elevated blood pressure at E20. Male offspring from L-NAME mothers had a markedly reduced birth weight and developed postnatal catch-up growth during lactation. Some L-NAME newborns presented some limb defects but were not selected in this study (1/3 of all pups). Improved glucose tolerance and hyperphagia after fasting were found in 3-month-old L-NAME rat but not thereafter. In 9-month-old L-NAME rats, a moderate increase of food intake during the light phase and, after fasting, an augmentation of plasma insulin and a reduction of brown adipose tissue (BAT) deposit were found associated with an increased expression of UCP-1 mRNA in this tissue.

Conclusions: Despite IUGR and postnatal catch up growth, male rats exposed to L-NAME did not develop metabolic diseases when limb defects were not induced by L-NAME. We postulate that maternal hypertension during late gestation is not a major 'programming' metabolic factor for offspring.
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http://dx.doi.org/10.1016/j.metabol.2012.09.006DOI Listing
March 2013

Maternal calorie restriction modulates placental mitochondrial biogenesis and bioenergetic efficiency: putative involvement in fetoplacental growth defects in rats.

Am J Physiol Endocrinol Metab 2013 Jan 23;304(1):E14-22. Epub 2012 Oct 23.

Université Lille Nord de France, F-59000 Lille, France.

Low birth weight is associated with an increased risk for developing type 2 diabetes and metabolic diseases. The placental capacity to supply nutrients and oxygen to the fetus represents the main determiner of fetal growth. However, few studies have investigated the effects of maternal diet on the placenta. We explored placental adaptive proteomic processes implicated in response to maternal undernutrition. Rat term placentas from 70% food-restricted (FR30) mothers were used for a proteomic screen. Placental mitochondrial functions were evaluated using molecular and functional approaches, and ATP production was measured. FR30 drastically reduced placental and fetal weights. FR30 placentas displayed 14 proteins that were differentially expressed, including several mitochondrial proteins. FR30 induced a marked increase in placental mtDNA content and changes in mitochondrial functions, including modulation of the expression of genes implicated in biogenesis and bioenergetic pathways. FR30 mitochondria showed higher oxygen consumption but failed to maintain their ATP production. Maternal undernutrition induces placental mitochondrial abnormalities. Although an increase in biogenesis and bioenergetic efficiency was noted, placental ATP level was reduced. Our data suggest that placental mitochondrial defects may be implicated in fetoplacental pathologies.
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http://dx.doi.org/10.1152/ajpendo.00332.2012DOI Listing
January 2013

Prenatal fasudil exposure alleviates fetal growth but programs hyperphagia and overweight in the adult male rat.

Eur J Pharmacol 2012 Aug 7;689(1-3):278-84. Epub 2012 Jun 7.

Univ Lille Nord de France, Unité Environnement Périnatal et Croissance, EA 4489, Faculté de Médecine, Pôle Recherche, Bâtiment SN4, Villeneuve d'Ascq, IFR 114, 59045 Lille, France.

Numerous data indicate that Rho kinase inhibitors, such as Fasudil, may constitute a novel therapy for cardiovascular and metabolic diseases. We evaluated long-term effects of exposure to Fasudil during late gestation (10 mg/day) in male rat offspring from birth until 9 months. We also analyzed its effects in offspring from hypertensive mothers treated with a nitric oxide synthesis inhibitor (L-NAME; 50 mg/day). Prenatal exposure to Fasudil did not affect birth weight, but increased body weight from postnatal day 7 (P7) to 9 months. In intrauterine growth-restricted (IUGR) fetuses exposed to L-NAME, maternal Fasudil treatment increased birth weight. At P42 and P180, rats exposed to Fasudil and L-NAME showed alterations of their food intake as well as an increased basal glycemia associated with mild glucose intolerance at 6 months which was also observed in Fasudil-exposed rats. In 9 month-old rats, exposure to Fasudil increased the daily food intake as well as hypothalamic mRNA level of the orexigenic NPY peptide without modulation of the anorexigenic POMC gene expression. Altogether, our data suggest that prenatal Fasudil exposure alleviates fetal growth in IUGR rats, but programs long-term metabolic disturbances including transient perturbations of glucose metabolism, a persistent increase of body weight gain, hyperphagia and an augmented expression of hypothalamic NPY orexigenic gene. We postulate that Fasudil treatment during perinatal periods may predispose individuals to the development of metabolic disorders.
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http://dx.doi.org/10.1016/j.ejphar.2012.05.040DOI Listing
August 2012

Development of a new illumination procedure for photodynamic therapy of the abdominal cavity.

J Biomed Opt 2012 Mar;17(3):038001

University Lille Nord de France, INSERM, U703, Lille University Hospital, Lille, France.

A homogeneous illumination of intra-abdominal organs is essential for successful photodynamic therapy of the abdominal cavity. Considering the current lack of outstanding light-delivery systems, a new illumination procedure was assessed. A rat model of peritoneal carcinomatosis was used. Four hours after intraperitoneal injection of hexaminolevulinate, a square illuminating panel connected to a 635-nm laser source was inserted vertically into the abdominal cavity. The abdominal incision was sutured and a pneumoperitoneum created prior to illumination. Light dosimetry was based on the calculation of the peritoneal surface by MRI. The rats were treated with a light dose of 20, 10, 5 or 2.5 J/cm(2) administered continuously with an irradiance of 7 mW/cm(2). The homogeneity of the cavity illumination was assessed by quantification of the photobleaching of the tumor lesions according to their localization and by scoring of that of the liver and of the bowel immediately after treatment. Photobleaching quantification for tumor lesions relied on the calculation of the fluorescence intensity ratio (after/before treatment) after recording of the lesions during blue-light laparoscopy and determination of their fluorescence intensity with Sigmascan Pro software. The procedure led to a homogeneous treatment of the abdominal cavity. No statistical difference was observed for the photobleaching values according to the localization of the lesions on the peritoneum (p=0.59) and photobleaching of the liver and of the intestine was homogeneous. We conclude that this procedure can successfully treat the major sites involved in peritoneal carcinomatosis.
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http://dx.doi.org/10.1117/1.JBO.17.3.038001DOI Listing
March 2012

Maternal hypertension induces tissue-specific modulations of the apelinergic system in the fetoplacental unit in rat.

Peptides 2012 May 15;35(1):136-8. Epub 2012 Mar 15.

Univ Lille Nord de France, Unité Environnement Périnatal et Croissance, EA 4489, Equipe dénutritions maternelles périnatales, Université de Lille 1, Bâtiment SN4, F-59655 Villeneuve d'Ascq, France.

Apelin and its receptor APJ are expressed in fetal tissues but their function and regulation remain largely unknown. In rat, maternal treatment with a nitric oxide synthase inhibitor inducing hypertension was used to investigate apelin plasma levels in mother/fetus pairs and on the gene expression level of the apelin/APJ system in fetal tissues and placenta. At term, plasma levels of apelin were not modulated but APJ expression was increased in placenta and lung but reduced in heart. Apelin expression was increased only in the heart. We postulate that the apelinergic system may control fetal growth and cardiovascular functions in utero.
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http://dx.doi.org/10.1016/j.peptides.2012.03.005DOI Listing
May 2012

The PACAP-regulated gene selenoprotein T is highly induced in nervous, endocrine, and metabolic tissues during ontogenetic and regenerative processes.

Endocrinology 2011 Nov 6;152(11):4322-35. Epub 2011 Sep 6.

INSERM, U982, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Sciences Faculty, University of Rouen, Place Emile Blondel, F-76821 Mont-Saint-Aignan, France.

Selenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease. Up to now, 25 selenoprotein-encoding genes were identified in mammals, but the spatiotemporal distribution, regulation, and function of some of these selenium-containing proteins remain poorly documented. Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein, is regulated by the trophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) in differentiating but not mature adrenomedullary cells. In fact, our analysis revealed that, in rat, SelT is highly expressed in most embryonic structures, and then its levels decreased progressively as these organs develop, to vanish in most adult tissues. In the brain, SelT was abundantly expressed in neural progenitors in various regions such as the cortex and cerebellum but was undetectable in adult nervous cells except rostral migratory-stream astrocytes and Bergmann cells. In contrast, SelT expression was maintained in several adult endocrine tissues such as pituitary, thyroid, or testis. In the pituitary gland, SelT was found in secretory cells of the anterior lobe, whereas in the testis, the selenoprotein was present only in spermatogenic and Leydig cells. Finally, we found that SelT expression is strongly stimulated in liver cells during the regenerative process that occurs after partial hepatectomy. Taken together, these data show that SelT induction is associated with ontogenesis, tissue maturation, and regenerative mechanisms, indicating that this PACAP-regulated selenoprotein may play a crucial role in cell growth and activity in nervous, endocrine, and metabolic tissues.
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http://dx.doi.org/10.1210/en.2011-1246DOI Listing
November 2011