Effects of perinatal exercise on offspring metabolic health : body composition, pancreatic function and energy substrates management.

Les maladies métaboliques sont en pleine expansion dans nos sociétés actuelles et constituent un enjeu de santé publique majeur. Les antécédents familiaux, l'environnement et les habitudes de vie de l'individu vont jouer un rôle dans la susceptibilité à certains de ces désordres métaboliques. Sur la base de données épidémiologiques, un lien a été établi entre environnement durant les premières phases de la vie et survenue de pathologies à l'âge adulte conduisant au concept de DOHaD. L'objectif de ce travail était d'étudier, à partir d'un modèle murin, les conséquences de l'exercice physique quotidien de la mère pendant la gestation ou la lactation sur la composition corporelle, la fonction pancréatique et la gestion des substrats énergétiques de la descendance à plus ou moins long terme. L'entraînement maternel avant et pendant la gestation est associé à des modifications de la structure et de la fonction du pancréas de la descendance et semble modifier sa gestion des substrats énergétiques à tous les âges. L'exercice de la mère est également associé à une moindre prise de poids de la descendance et limite sa prise de masse grasse lorsqu'elle est soumise à un régime gras et sucré. L'exercice physique de la mère durant la lactation va modifier la composition du lait et la fonction pancréatique de la descendance. Cependant, il est associé à une augmentation du poids corporel de la descendance adulte mais semble la protéger contre l'insulino-résistance induite par la séparation maternelle. La pratique d'un exercice physique quotidien pendant la gestation et/ou la lactation semble donc modifier le développement et la maturation de certains organes (pancréas, tissu adipeux, foie, muscle squelettique) de la descendance ainsi que sa gestion des substrats énergétiques. Les conséquences de cet entraînement maternel sur la descendance vont être plus ou moins bénéfiques selon son âge et selon son environnement nutritionnel. Ce travail de thèse vient compléter les travaux menés dans le cadre des DOHaD et renforce l'idée que l'environnement lors des premières phases de la vie va avoir des conséquences à plus ou moins long terme sur la santé de l'individu.Prevalence of metabolic diseases is growing up in our modern societies and constitutes a major public health concern. Family history, environment and lifestyle play a role in the susceptibility to several metabolic disorders. Based on epidemiological data, a link has been established between the environment during the first stages of life and diseases occurrence in adulthood leading to the concept of DOHaD. The aim of this work was to study, using a murine model, the effect of daily maternal exercise during gestation or lactation on offspring body composition, pancreatic function and energy substrates handling on a short- and a long-term basis. Maternal training before and during gestation is associated with changes in offspring pancreas structure and function and in energy substrates handling at all ages. Maternal exercise also decreases offspring body weight gain and fat mass gain when exposed to a high-fat/high sucrose diet. Maternal physical exercise during lactation modifies milk composition and offspring pancreatic function. However, it is associated to an increase in offspring body weight in adulthood but seems to protect against the insulin resistance induced by maternal separation. In conclusion, daily physical exercise during gestation and/or lactation modifies offspring organs development and maturation (such as pancreas, adipose tissue, liver, skeletal muscle) and its energy substrates handling. Maternal training consequences on offspring can be either beneficial or deleterious depending on its age and on its nutritional environment. This work is complementary to studies conducted in the framework of the DOHaD concept and strengthens the idea that the environment during the first stages of life will have short- to long-term impacts on the health of the individual

Effets de l'entraînement physique périnatal sur la santé métabolique de la descendance : composition corporelle, fonction pancréatique et gestion des substrats énergétiques

Prevalence of metabolic diseases is growing up in our modern societies and constitutes a major public health concern. Family history, environment and lifestyle play a role in the susceptibility to several metabolic disorders. Based on epidemiological data, a link has been established between the environment during the first stages of life and diseases occurrence in adulthood leading to the concept of DOHaD. The aim of this work was to study, using a murine model, the effect of daily maternal exercise during gestation or lactation on offspring body composition, pancreatic function and energy substrates handling on a short- and a long-term basis. Maternal training before and during gestation is associated with changes in offspring pancreas structure and function and in energy substrates handling at all ages. Maternal exercise also decreases offspring body weight gain and fat mass gain when exposed to a high-fat/high sucrose diet. Maternal physical exercise during lactation modifies milk composition and offspring pancreatic function. However, it is associated to an increase in offspring body weight in adulthood but seems to protect against the insulin resistance induced by maternal separation. In conclusion, daily physical exercise during gestation and/or lactation modifies offspring organs development and maturation (such as pancreas, adipose tissue, liver, skeletal muscle) and its energy substrates handling. Maternal training consequences on offspring can be either beneficial or deleterious depending on its age and on its nutritional environment. This work is complementary to studies conducted in the framework of the DOHaD concept and strengthens the idea that the environment during the first stages of life will have short- to long-term impacts on the health of the individual.Les maladies métaboliques sont en pleine expansion dans nos sociétés actuelles et constituent un enjeu de santé publique majeur. Les antécédents familiaux, l'environnement et les habitudes de vie de l'individu vont jouer un rôle dans la susceptibilité à certains de ces désordres métaboliques. Sur la base de données épidémiologiques, un lien a été établi entre environnement durant les premières phases de la vie et survenue de pathologies à l'âge adulte conduisant au concept de DOHaD. L'objectif de ce travail était d'étudier, à partir d'un modèle murin, les conséquences de l'exercice physique quotidien de la mère pendant la gestation ou la lactation sur la composition corporelle, la fonction pancréatique et la gestion des substrats énergétiques de la descendance à plus ou moins long terme. L'entraînement maternel avant et pendant la gestation est associé à des modifications de la structure et de la fonction du pancréas de la descendance et semble modifier sa gestion des substrats énergétiques à tous les âges. L'exercice de la mère est également associé à une moindre prise de poids de la descendance et limite sa prise de masse grasse lorsqu'elle est soumise à un régime gras et sucré. L'exercice physique de la mère durant la lactation va modifier la composition du lait et la fonction pancréatique de la descendance. Cependant, il est associé à une augmentation du poids corporel de la descendance adulte mais semble la protéger contre l'insulino-résistance induite par la séparation maternelle. La pratique d'un exercice physique quotidien pendant la gestation et/ou la lactation semble donc modifier le développement et la maturation de certains organes (pancréas, tissu adipeux, foie, muscle squelettique) de la descendance ainsi que sa gestion des substrats énergétiques. Les conséquences de cet entraînement maternel sur la descendance vont être plus ou moins bénéfiques selon son âge et selon son environnement nutritionnel. Ce travail de thèse vient compléter les travaux menés dans le cadre des DOHaD et renforce l'idée que l'environnement lors des premières phases de la vie va avoir des conséquences à plus ou moins long terme sur la santé de l'individu

Maternal training during lactation modifies breast milk fatty acid composition and male offspring glucose homeostasis in rat

International audienceThe perinatal exposome can modify offspring metabolism and health later in life. Within this concept, maternal exercise during gestation has been reported modifying offspring glucose sensing and homeostasis, while the impact of such exercise during lactation is little-known. We thus aimed at evaluating short-and long-term effects of it on offspring pancreatic function, assuming a link with changes in breast milk composition. Fifteen-week-old primiparous female Wistar rats exercised during lactation at a constant submaximal intensity (TR) or remained sedentary (CT). Male offspring were studied at weaning and at 7 months of age for growth, pancreas weight, glycemia and insulin responses. Milk protein content was determined by the bicinchoninic acid assay (BCA colorimetric method), and lipid content and fatty acid composition by gas chromatography. Mature milk from TR rats contained significantly less saturated (-7%) and more monounsaturated (+18%) and polyunsaturated (PUFA +12%) fatty acids compared to CT rats, with no difference in total lipid and protein concentrations. In offspring from TR vs CT mothers, fasting glycemia was lower, pancreas weight was higher with a lower insulin content (-37%) at weaning. Such outcomes were correlated with milk PUFA levels and indices of desaturase or elongase activities. These effects were no longer present at 7 months, whereas a more efficient muscle insulin sensitivity was observed. Maternal training during lactation led to a specific milk phenotype that was associated with a short-term impact on glucose homeostasis and pancreatic function of the male offspring

Combined effects of citrulline supplemntation and physical training in healthy adult rats

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Short-term and long-term effects of submaximal maternal exercise on offspring glucose homeostasis and pancreatic function

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Maternal exercise modifies body composition and energy substrates handling in male offspring fed a high-fat/high-sucrose diet

International audienceKey points: Maternal training during gestation enhances offspring body composition and energy substrates handling in early adulthood. Offspring nutrition also plays a role as some beneficial effects of maternal training during gestation disappear after consumption of a high-fat diet.Abstract: Maternal exercise during gestation has been reported to modify offspring metabolism and health. Whether these effects are exacerbated when offspring are receiving a high-fat diet remains unclear. Our purpose was to evaluate the effect of maternal exercise before and during gestation on the offspring fed a high-fat/high-sucrose diet (HF) by assessing its body composition, pancreatic function and energy substrates handling by two major glucose-utilizing tissues: liver and muscle. Fifteen-week-old nulliparous female Wistar rats exercised 4 weeks before as well as during gestation at a constant submaximal intensity (TR) or remained sedentary (CT). At weaning, pups from each group were fed either a standard diet (TRCD or CTCD) or a high-fat/high-sucrose diet (TRHF or CTHF) for 10 weeks. Offspring from TR dams gained less weight compared to those from CT dams. Selected fat depots were larger with the HF diet compared to control diet (CD) but significantly smaller in TRHF compared to CTHF. Surprisingly, the insulin secretion index was higher in islets from HF offspring compared to CD. TR offspring showed a higher muscle insulin sensitivity estimated by the ratio of phosphorylated protein kinase B to total protein kinase B compared with CT offspring (+48%, P < 0.05). With CD, permeabilized isolated muscle fibres from TR rats displayed a lower apparent affinity constant (Km ) for pyruvate and palmitoyl coenzyme A as substrates compared to the CT group (-46% and -58%, respectively, P < 0.05). These results suggest that maternal exercise has positive effects on young adult offspring body composition and on muscle carbohydrate and lipid metabolism depending on the nutritional status

Maternal exercise before and during gestation modifies liver and muscle mitochondria in rat offspring

International audienceIt is now well established that the intrauterine environment is of major importance for offspring health during later life. Endurance training during pregnancy is associated with positive metabolic adjustments and beneficial effects on the balance between pro-oxidants and antioxidants (redox state) in the offspring. Our hypothesis was that these changes could rely on mitochondrial adaptations in the offspring due to modifications of the fetal environment induced by maternal endurance training. Therefore, we compared the liver and skeletal muscle mitochondrial function and the redox status of young rats whose mothers underwent moderate endurance training (treadmill running) before and during gestation (T) with those of young rats from untrained mothers (C). Our results show a significant reduction in the spontaneous H2O2 release by liver and muscle mitochondria in the T versus C offspring (P<0.05). These changes were accompanied by alterations in oxygen consumption. Moreover, the percentage of short-chain fatty acids increased significantly in liver mitochondria from T offspring. This may lead to improvements in the fluidity and the flexibility of the membrane. In plasma, glutathione peroxidase activity and protein oxidation were significantly higher in T offspring than in C offspring (P<0.05). Such changes in plasma could represent an adaptive signal transmitted from mothers to their offspring. We thus demonstrated for the first time, to our knowledge, that it is possible to act on bioenergetic function including alterations of mitochondrial function in offspring by modifying maternal physical activity before and during pregnancy. These changes could be crucial for the future health of the offspring

Impact of maternal low-level cadmium exposure on glucose and lipid metabolism of the litter at different ages after weaning

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Overexpression of Gjb4 impairs cell proliferation and insulin secretion in primary islet cells

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