Maternal Protein Restriction in Rats Alters Postnatal Growth and Brain Lipid Sensing in Female Offspring

Perinatal nutrition is a key player in the susceptibility to developing metabolic diseases in adulthood, leading to the concept of “metabolic programming”. The aim of this study was to assess the impact of maternal protein restriction during gestation and lactation on glucose homeostasis and eating behaviour in female offspring. Pregnant rats were fed a normal or protein-restricted (PR) diet and followed throughout gestation and lactation. Body weight, glucose homeostasis, and eating behaviour were evaluated in offspring, especially in females. Body weight gain was lower in PR dams during lactation only, despite different food and water intakes throughout gestation and lactation. Plasma concentration of leptin, adiponectin and triglycerides increased drastically before delivery in PR dams in relation to fat deposits. Although all pups had identical birth body weight, PR offspring body weight differed from control offspring around postnatal day 10 and remained lower until adulthood. Offspring glucose homeostasis was mildly impacted by maternal PR, although insulin secretion was reduced for PR rats at adulthood. Food intake, satiety response, and cerebral activation were examined after a lipid preload and demonstrated some differences between the two groups of rats. Maternal PR during gestation and lactation does induce extrauterine growth restriction, accompanied by alterations in maternal plasma leptin and adiponectin levels, which may be involved in programming the alterations in eating behaviour observed in females at adulthood

Maternal Protein Restriction in Rats Alters Postnatal Growth and Brain Lipid Sensing in Female Offspring

Perinatal nutrition is a key player in the susceptibility to developing metabolic diseases in adulthood, leading to the concept of “metabolic programming”. The aim of this study was to assess the impact of maternal protein restriction during gestation and lactation on glucose homeostasis and eating behaviour in female offspring. Pregnant rats were fed a normal or protein-restricted (PR) diet and followed throughout gestation and lactation. Body weight, glucose homeostasis, and eating behaviour were evaluated in offspring, especially in females. Body weight gain was lower in PR dams during lactation only, despite different food and water intakes throughout gestation and lactation. Plasma concentration of leptin, adiponectin and triglycerides increased drastically before delivery in PR dams in relation to fat deposits. Although all pups had identical birth body weight, PR offspring body weight differed from control offspring around postnatal day 10 and remained lower until adulthood. Offspring glucose homeostasis was mildly impacted by maternal PR, although insulin secretion was reduced for PR rats at adulthood. Food intake, satiety response, and cerebral activation were examined after a lipid preload and demonstrated some differences between the two groups of rats. Maternal PR during gestation and lactation does induce extrauterine growth restriction, accompanied by alterations in maternal plasma leptin and adiponectin levels, which may be involved in programming the alterations in eating behaviour observed in females at adulthood

Impact of maternal protein restriction on the molecular mechanisms of neuronal differentiation in the fetal hypothalamus in rats

Un apport insuffisant en protéines au cours de la période périnatale augmente le risque de développer des désordres métaboliques et des troubles du comportement alimentaire. Chez les rongeurs, les conséquences d’une malnutrition maternelle sur l’hypothalamus sont visibles dès les premières semaines de vie par des modifications des circuits neuronaux et de la densité neuronale dans les zones impliquées dans la régulation de l’homéostasie énergétique. Nous avons émis l’hypothèse que ces effets pourraient être liés à des altérations du développement cérébral dès le stade fœtal. L’objectif de cette thèse était de déterminer, par des approches cellulaires et moléculaires, l’impact d’une restriction protéique maternelle au cours de la gestation sur la différenciation neuronale dans l’hypothalamus de fœtus de rats au 17ème jour de gestation. Nous avons observé une réduction du nombre total de cellules hypothalamiques ainsi qu’une augmentation du nombre de progéniteurs engagés dans la voie neuronale, suggérant une altération de la prolifération et de la différenciation cellulaires. Une analyse du transcriptome a mis en évidence des modifications du métabolisme mitochondrial et de la régulation post-transcriptionnelle de l’expression des gènes chez les fœtus restreints en protéines. Nous avons également montré une altération modérée des paramètres épigénétiques conditionnant la conformation de la chromatine. Nos résultats montrent qu’un déficit en acides aminés pendant la vie fœtale entraîne des modifications du métabolisme cellulaire associés à des altérations de l’expression des gènes qui influencent le destin cellulaire des cellules souches neurales.Insufficient protein intake during the perinatal period increases the risk of developing metabolic and eating disorders. In rodents, the effects of maternal malnutrition on the hypothalamus are visible from the first weeks of life as changes in neuronal circuits and neuronal density in regions involved in the control of energy homeostasis. We hypothesized that these effects could be related to alterations in brain development during fetal life. The objective of this study was to determine, using cellular and molecular approaches, the impact of a maternal protein restriction during gestation on neuronal differentiation in the hypothalamus of rat fetuses on day 17 of gestation. We observed a decrease in the total number of hypothalamic cells as well as an increase in the number of neuronal- committed progenitors, suggesting impaired cell proliferation and differentiation. Transcriptome analysis revealed alterations in mitochondrial metabolism and post-transcriptional regulation of gene expression in protein restricted fetuses. We also showed a moderate alteration of the epigenetic parameters that control chromatin conformation. Our results show that an amino acid deficiency during fetal life leads to changes in cellular metabolism associated with alterations in the expression of genes, ultimately leading to modifications of neural stem cell fate

La différenciation neuronale de l'hypothalamus : impact d'une restriction protéique périnatale sur les mécanismes moléculaires

il s'agit d'un type de produit dont les métadonnées ne correspondent pas aux métadonnées attendues dans les autres types de produit : DISSERTATIONMasterLa différenciation neuronale de l'hypothalamus : impact d'une restriction protéique périnatale sur les mécanismes moléculaire

Maternal malnutrition during gestation alters fetal hypothalamus development

International audienc

Maternal malnutrition during gestation alters fetal hypothalamus development

International audienc

Balanced food intake after weaning reverses the inapropriate food preference in offspring of low-protein diet fed dams correlated with reward pathway modifications

National audienc

Maternal nutrition and epitranscriptomics

National audienc

Maternal malnutrition and hypothalamic development

National audienc

Maternal nutrition and epitranscriptomics

National audienc