No description available.

Une malnutrition périnatale sensibilise au développement, à l’âge adulte, du syndrome métabolique. Ce syndrome est associé à une altération de l’équilibre entre prise alimentaire et dépense énergétique. L’axe hypothalamo-adipocytaire, constitué du système nerveux central et du tissu adipeux, joue un rôle majeur dans le contrôle du métabolisme. En effet, ces deux tissus vont, via la leptine, être capables de réguler la prise alimentaire et la dépense énergétique. Peu de travaux ont porté sur les conséquences de stress périnataux sur la mise en place de l’axe hypothalamo-adipocytaire chez le nouveau-né.Nous avons entrepris, en ciblant nos travaux sur la leptine, d’analyser les conséquences d’une dénutrition maternelle périnatale (DMP) de 50% (modèle FR50) sur la mise en place de cet axe chez le raton de la naissance au sevrage.Les animaux témoins présentent un pic de leptine autour de la deuxième semaine de vie qui est fortement réduit chez les ratons FR50. Cette diminution est associée à une altération des connexions hypothalamiques des neurones à POMC. La réduction des taux de leptine chez le nouveau-né est conjointe à une diminution des concentrations de leptine dans le plasma des mères et dans le lait, ce qui montre que la période de lactation et le statut nutritionnel maternel jouent un rôle capital dans les mécanismes de programmation. En périphérie, les animaux FR50 présentent un changement transitoire de phénotype du tissu adipeux périgonadique, avec l’apparition d’un phénotype de type brun. L’ensemble de nos travaux indique que la DMP modifie la mise en place de l’axe hypothalamo-adipocytaire et que la période de lactation constitue une période clé pour la programmation de mécanismes impliqués dans le contrôle du métabolisme énergétique. / Perinatal malnutrition sensitizes to the development of chronic adult diseases such as the metabolic syndrome. These metabolic disorders frequently result from an imbalance between food intake and energy expenditure.The brain-adipose axis (BAA) that is constituted from central nervous system and adipose tissues plays a crucial role in the regulation of metabolism. These two tissues indeed control both food intake and energy expenditure, via different factors such as leptin. Little is known concerning the consequences of perinatal stress on the development of BAA in newborns,.The major goal of my Ph D was to analyze the consequences of a 50% maternal perinatal undernutrition (FR50 model) on the development of BAA in male rat from birth to weaningControl animals exhibited a plasma surge of leptin around the second week of life while this peak was drasticallyreduced in FR50 pups. This reduction is associated with an alteration of the hypothalamic projections of POMC nerve fibers. The decreased leptin plasma levels in FR50 pups is accompanied by a reduction of leptin concentration both in plasma from mothers as in the milk from undernourished mothers, reinforcing the idea that lactation and nutritional status of the mother during this period are key “programming” factors. Interestingly, in postnatal day (PND) 21 FR50 animals, perigonadal adipose tissue exhibited a transient modification with the acquisition of a brown-like Altogether, our results indicate that maternal perinatal undernutrition modifies the development of the BAA and that lactation is a critical timewindow for the programming of mechanisms involved in the regulation of energy metabolism.

Thesis (Ph. D.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 183-273).

Neuropeptide Y (NPY) has been shown to play a critical role in the regulation of bone metabolism by signalling via Y1 and Y2 receptors. Centrally, hypothalamic Y2 but not Y1 receptors are important for the action of NPY on bone formation and osteoblast activity. This project investigates how the NPY system, in particular, the Y1 receptor, influences bone metabolism peripherally by examining a range of conditional and germline knockout mice using in vitro and in vivo techniques. Revealing the possibility of a direct role for the Y1 receptor on bone cells, we demonstrate the presence of Y1 but not Y2 receptor mRNA in osteoblasts by in situ hybridisation on femur sections and RT-PCR on bone marrow stromal cells (BMSCs). In addition, we show that NPY mRNA is also expressed by osteoblasts suggesting that locally produced NPY may directly influence bone cell activity. In order to investigate the role of osteoblastic Y1 receptors, mice with selective osteoblastic deletion of the Y1 receptor under control of the osteoblast-specific α1(I)-collagen promotor were generated. In male mice, osteoblast-specific Y1 receptor deletion resulted in a marked increase in femoral trabecular bone volume, trabecular number, cortical bone volume and cortical thickness due to elevated osteoblast activity as shown by increased mineral apposition rate and bone formation rate. Further in vitro investigations using cells isolated from germline and conditional knockout mice demonstrated that NPY inhibits the proliferation of BMSCs via the Y1 receptor and that mineralisation is enhanced in vitro in the absence of NPY or osteoblastic Y1 receptors. Moreover, this study reveals a critical role for the NPY system via Y1 receptors in the proliferation and differentiation of mesenchymal stem cells and osteoprogenitor cells. Together these data demonstrate a direct role for the NPY system via Y1 receptors on the proliferation and differentiation of osteoblastic progenitor cells as well as on regulating the activity of mature osteoblasts, thereby altering bone formation both in vitro and in vivo. Understanding the action of NPY on osteoblasts to regulate bone metabolism could have powerful therapeutic implications for stimulating bone accrual in diseases such as osteoporosis.

Thèses (Ph.D.)--Université de Sherbrooke (Canada), 2001. / Titre de l'écran-titre (visionné le 15 août 2006). Publié aussi en version papier.

Thesis (Ph.D.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 183-273) Also available in print.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

No description available.

Developmental changes within the hypothalamus are necessary for maturation of the reproductive neuroendocrine axis. Recent reports have implicated several neuronal networks in this process, but genes involved in their regulation have not been elucidated. Using a well-established model for nutritional induction of precocious puberty, objectives were to 1) use microarray technology to examine changes in gene expression within the arcuate nucleus (ARC) of the hypothalamus in pre-pubertal heifers fed high or low-concentrate diets, and 2) determine if high-concentrate diets are required for nutritional induction of precocious puberty. In Experiment 1, early-weaned, cross-bred heifers were fed either a high-forage/low-gain (HF/LG; 0.45 kg/d) or a highconcentrate/ high-gain (HC/HG; 0.91 kg/d) diet for 91 d. Analysis of microarray data indicated that 346 genes were differentially expressed (P < 0.05) between HC/HG and HF/LG heifers. Expression of three key metabolic genes [neuropeptide Y (NPY), agoutirelated protein (AGRP), and growth hormone receptor (GHR)] observed to be differentially expressed in the microarray analysis was investigated further by quantitative PCR. Real-time RT-PCR indicated that expression of NPY, AGRP and GHR was lower (P < 0.05) in HC/HG compared to HF/LG heifers. In contrast, concentrations of insulin (P < 0.05), IGF-1 (P < 0.002) and leptin (P = 0.1) were greater in HC/HG compared to HF/LG. For Experiment 2, 48 heifers were used in 2 replicates (24 heifers/replicate) in a 2 x 2 factorial design to examine the roles of diet type (HF vs HC) and rate of gain (LG, 0.45 kg/d vs HG, 0.91 kg/d) on age at puberty. Heifers were fed HC/HG, HC/LG, HF/HG or HF/LG (n = 12/group) for 14 wk, and then switched to a common growth diet (0.68 kg/d) until puberty. Heifers in both HG groups reached puberty at a younger age (54.5 ± 1.8 wk) than heifers in both LG groups (60.2 ± 1.9 wk; P < 0.04). A marked increase (P < 0.01) in serum concentrations of leptin occurred in HC/HG heifers between 24 and 30 wk of age. This increase in circulating leptin was not observed in other groups. Overall, results indicate that nutritional regulation of reproductive neuroendocrine development involves the control of NPY, AGRP and GHR expression. The abrupt increase noted for circulating leptin in heifers fed HC/HG diets, if timed and sustained appropriately, could represent an important temporal cue for activation of the neuroendocrine system and the onset of puberty.