Effets de la protéine de morue sur la sensibilité à l'insuline chez des hommes et des femmes résistants à l'insuline

Dans le cadre de cette thèse, nous nous sommes intéressés aux effets de la consommation de protéine de morue pendant quatre semaines sur la sensibilité à l' insuline chez des hommes et des femmes ayant un surpoids ou obèses et résistants à l'insuline. Nous avons noté une amélioration de la sensibilité à l' insuline et une forte tendance à un meilleur ±disposition index¿ (fonction cellules-β x sensibilité à l'insuline) lorsque les sujets ont consommé la protéine de morue comparativement au mélange de protéines animales (BPVOL). Nous avons également observé que seulement le BPVOL a entraîné une diminution des concentrations plasmatiques de cholestérol total, de cholestérol des LDL et d'apolipoprotéine B totale. Par la suite, nous avons voulu identifier des mécanismes par lesquels la protéine de morue exerce des effets bénéfiques sur la sensibilité à l' insuline. Au niveau des marqueurs de l'inflammation, la protéine de morue a provoqué une diminution de la concentration plasmatique de la protéine C-réactive hautement sensible tandis que le BPVOL a eu tendance à induire une augmentation, entraînant une différence significative entre les deux régimes. Toutefois, les changements des concentrations plasmatiques d'interleukine-6, du facteur de nécrose tumorale-α et d'adiponectine ont été similaires entre les deux régimes. Au niveau de la voie de signalisation insulinique, une stimulation à l'insuline a entraîné une augmentation de l'activation de la PI 3-kinase associée à IRS-1 et de la glycogène synthase suite à la consommation de la protéine de morue. De plus, une augmentation de la phosphorylation de IRS-l sur Ser636/639 a été observée avec le BPVOL alors que la protéine de morue n'a pas eu d'effet, ce qui pourrait indiquer une augmentation de la stimulation de la voie mTORlS6K1 lors de la consommation de BPVOL. Les deux régimes n'ont pas eu d'effet sur la morphologie et la capacité métabolique du muscle. Enfin, ils ont affecté différemment la concentration plasmatique à jeun de taurine. Toutefois, il est peu probable qu'un seul acide aminé soit responsable de tous les effets de la protéine de morue. Des études supplémentaires sont nécessaires pour mieux identifier les acides aminés impliqués. Donc, l'étude constituant cette thèse a permis de démontrer que la protéine de morue pourrait améliorer le métabolisme du glucose et potentiellement ralentir la progression vers le diabète de type 2. Les mécanismes impliqués dans l'effet insulinosensibilisateur de la protéine de morue demeurent à être approfondis

Le stress de chaleur chez la vache laitière : effets sur les performances de production des troupeaux laitiers québécois

L’objectif des travaux effectués dans le cadre de cette thèse étaient de fournir de l’information concernant les impacts du stress de chaleur dans les troupeaux laitiers québécois. Le programme de recherche présenté a été conçu en prenant en considération le climat de la province et l’unicité du contexte de production canadien. La relation entre les conditions climatiques mesurées dans six étables laitières québécoises et celles mesurées à des stations météorologiques a d’abord été investiguée. L’objectif était de vérifier si les données collectées aux stations météorologiques pouvaient servir de substitut aux données des étables afin de juger adéquatement du niveau de stress de chaleur des animaux. Les résultats ont démontré que la température ambiante mesurée à l’intérieur des étables était significativement (P 0,05) n’a été mesurée entre les productions de lait et de lactose et la durée des épisodes de stress de chaleur. Dans la troisième étude, les performances de production des vaches de la banque de données décrite précédemment ont été simulées pendant une période de référence (REF : 1971‒2000) et projetées pendant deux horizons futurs (FUT1: 2020‒2049; FL: 2050‒2079). L’objectif était de caractériser l’évolution des diminutions des composants laitiers associées au stress de chaleur et d’en chiffrer l’impact économique. Tout d’abord, les ITH quotidiens des trois périodes temporelles ont été calculés grâce aux données environnementales dérivées de six scénarios climatiques. Ensuite, le modèle élaboré dans la précédente étude a été adapté afin de projeter les performances de production des vaches pour les trois périodes mentionnées. Globalement, les scénarios climatiques utilisés dans cette étude ont démontré que la fréquence, l’intensité ainsi que la durée des épisodes de stress de chaleur pourront augmenter dans le FUT1 et dans le FL comparativement à la période de référence. Dans la région de l’Est du Québec, des pertes moyennes de gras et de protéines de 2405 ± 10 et de 1990 ± 7 kg/année par troupeau ont respectivement été projetées dans le FUT1 comparativement à REF. Dans la région du Sud-Ouest du Québec, des pertes moyennes de gras et de protéines de 2361 ± 147 et de 2057 ± 17 kg/année par troupeau ont respectivement été projetées dans le FUT1 comparativement à REF. Comparativement à REF, les diminutions projetées dans le futur (FUT1 et FL) se sont traduites par des pertes économiques moyennes allant de 5,02 à 7,07 can$/hl dans les troupeaux de l’Est du Québec et allant de 4,75 à 6,99 can$/hl dans les troupeaux du Sud-Ouest du Québec.The main objective of this thesis was to provide information about heat stress related production impacts in Québec dairy herds. The relationship between on-farm summer environmental conditions and data retrieved from local meteorological stations was first investigated on six dairy farms. Secondly, the relationship between measurements previously established was considered in order to verify if temperature-humidity index (THI) calculations with weather station data could be adapted to better represent on-farm conditions. The farms recruited in the study were located in two contrasting dairy regions of the Province: East (EQ) and Southwest Quebec (SWQ). Our results showed that in both regions ambient temperature (AT) was consistently higher (P 0.05) lower in SWQ compared to RH extracted from weather stations. Overall, this led to lower (P 0.05). Ultimately, heat stress lowered milk fat and protein production but had little effect on milk volume output. Further research is necessary to understand better the mechanism underlying the effects of sporadic low-to-medium-intensity heat stress on dairy productivity. The objective of the third study was to project milk performance of Holstein dairy cows under different climate scenarios through a reference period (REF: 1971–2000), near future (NF: 2020–2049) and distant future (DF: 2050–2079) using a predictive multivariate model. Moreover, this study provided information about the evolution of economic losses due to decreases in milk components associated with heat stress in Québec, Canada. Daily ambient temperature and relative humidity were derived from six climate scenarios in order to calculate daily THI through REF, NF and DF. Secondly, the model developed in the prior study was adapted to project annual milk performance of 71 dairy herds located in EQ and SWQ during the three aforementioned time horizons. Under NF climate conditions and relative to the reference period, projected fat and protein yields declined respectively by 2405 ± 10 and by 1990 ± 7 kg/yr per herd in EQ whereas decreases reached 2361 ± 147 and 2057 ± 17 kg/yr per herd in SWQ. Relative to the reference period, decreases in major milk components reached a maximum during DF in both regions. Ultimately, projected milk components declines resulted in average economic losses ranging from 5.02 to 7.07 can$/hL per EQ herds and from 4.75 to 6.99 can$/hL per SWQ herds

Profil d'expression moléculaire des tumeurs épithéliales ovariennes à faible et haut potentiel de malignité

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

An essential role for Ran GTPase in epithelial ovarian cancer cell survival

<p>Abstract</p> <p>Background</p> <p>We previously identified that Ran protein, a member of the Ras GTPase family, is highly expressed in high grade and high stage serous epithelial ovarian cancers, and that its overexpression is associated with a poor prognosis. Ran is known to contribute to both nucleocytoplasmic transport and cell cycle progression, but its role in ovarian cancer is not well defined.</p> <p>Results</p> <p>Using a lentivirus-based tetracycline-inducible shRNA approach, we show that downregulation of Ran expression in aggressive ovarian cancer cell lines affects cellular proliferation by inducing a caspase-3 associated apoptosis. Using a xenograft tumor assay, we demonstrate that depletion of Ran results in decreased tumorigenesis, and eventual tumor formation is associated with tumor cells that express Ran protein.</p> <p>Conclusion</p> <p>Our results suggest a role for Ran in ovarian cancer cell survival and tumorigenicity and suggest that this critical GTPase may be suitable as a therapeutic target.</p

Effect of sensory-based intervention on the increased use of food-related descriptive terms among restrained eaters

The goals of this pilot randomized controlled trial were to investigate and determine whether sensorybased intervention influenced the number and type of terms (descriptive and hedonic) used by restrained women to describe a certain food, and whether changes in the number of descriptive terms were associated with changes in intuitive eating. We collected data at baseline (T = 1), at the end of the intervention period (T = 2), and at 12 weeks post-intervention (T = 3) using the descriptive form and Intuitive Eating Scale (IES). At T = 1, 50 women were randomly assigned to an intervention group (sensory-based intervention) or a control group (waiting list). To determine the effect of intervention over time on the number of descriptive and hedonic terms, we conducted statistical analyses using mixed models. To determine associations between Intuitive Eating Scale subscales and the number of descriptive terms, we also calculated Spearman correlation coefficients. We noted a significant group-by-time interaction for descriptive terms associated with all senses (p < 0.04), except for a sight-related trend (p = 0.06). In comparison with T = 1, intervention group women at T = 2 and T = 3 showed a significant increase in descriptive terms associated with smell (p = 0.0002 and p = 0.03, respectively), taste (p = 0.001 and p = 0.01, respectively) and hearing (p = 0.04 and p = 0.0003, respectively). Among intervention group women, we noted a positive correlation between changes (T = 3 vs. T = 2) in the number of descriptive terms used and changes in reliance on internal hunger and satiety cues (r = 0.48; p = 0.04), as well as between changes (T = 3 vs. T = 1) in the number of descriptive terms used and changes in unconditional permission to eat (r = 0.45; p = 0.05). Overall, these data show that sensory-based intervention may help restrained women become more objective and enjoyably connected to food and their own bodies, which may promote a more intuitive approach to eating

Characterization of three new serous epithelial ovarian cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Cell lines constitute a powerful model to study cancer, and here we describe three new epithelial ovarian cancer (EOC) cell lines derived from poorly differentiated serous solid tumors (TOV-1946, and TOV-2223G), as well as the matched ascites for one case (OV-1946).</p> <p>Methods</p> <p>In addition to growth parameters, the cell lines were characterized for anchorage independent growth, migration and invasion potential, ability to form spheroids and xenografts in SCID mice.</p> <p>Results</p> <p>While all cell lines were capable of anchorage independent growth, only the TOV-1946 and OV-1946 cell lines were able to form spheroid and produce tumors. Profiling of keratins, p53 and Her2 protein expression was assessed by immunohistochemistry and western blot analyses. Somatic <it>TP53 </it>mutations were found in all cell lines, with TOV-1946 and OV-1946 harboring the same mutation, and none harbored the commonly observed somatic mutations in <it>BRAF</it>, <it>KRAS </it>or germline BRCA1/2 mutations found to recur in the French Canadian population. Conventional cytogenetics and spectral karyotype (SKY) analyses revealed complex karyotypes often observed in ovarian disease.</p> <p>Conclusion</p> <p>This is the first report of the establishment of matched EOC cell lines derived from both solid tumor and ascites of the same patient.</p

Necdin, a p53-Target Gene, Is an Inhibitor of p53-Mediated Growth Arrest

In vitro, cellular immortalization and transformation define a model for multistep carcinogenesis and current ongoing challenges include the identification of specific molecular events associated with steps along this oncogenic pathway. Here, using NIH3T3 cells, we identified transcriptionally related events associated with the expression of Polyomavirus Large-T antigen (PyLT), a potent viral oncogene. We propose that a subset of these alterations in gene expression may be related to the early events that contribute to carcinogenesis. The proposed tumor suppressor Necdin, known to be regulated by p53, was within a group of genes that was consistently upregulated in the presence of PyLT. While Necdin is induced following p53 activation with different genotoxic stresses, Necdin induction by PyLT did not involve p53 activation or the Rb-binding site of PyLT. Necdin depletion by shRNA conferred a proliferative advantage to NIH3T3 and PyLT-expressing NIH3T3 (NIHLT) cells. In contrast, our results demonstrate that although overexpression of Necdin induced a growth arrest in NIH3T3 and NIHLT cells, a growing population rapidly emerged from these arrested cells. This population no longer showed significant proliferation defects despite high Necdin expression. Moreover, we established that Necdin is a negative regulator of p53-mediated growth arrest induced by nutlin-3, suggesting that Necdin upregulation could contribute to the bypass of a p53-response in p53 wild type tumors. To support this, we characterized Necdin expression in low malignant potential ovarian cancer (LMP) where p53 mutations rarely occur. Elevated levels of Necdin expression were observed in LMP when compared to aggressive serous ovarian cancers. We propose that in some contexts, the constitutive expression of Necdin could contribute to cancer promotion by delaying appropriate p53 responses and potentially promote genomic instability

CCN3 modulates bone turnover and is a novel regulator of skeletal metastasis

The CCN family of proteins is composed of six secreted proteins (CCN1-6), which are grouped together based on their structural similarity. These matricellular proteins are involved in a large spectrum of biological processes, ranging from development to disease. In this review, we focus on CCN3, a founding member of this family, and its role in regulating cells within the bone microenvironment. CCN3 impairs normal osteoblast differentiation through multiple mechanisms, which include the neutralization of pro-osteoblastogenic stimuli such as BMP and Wnt family signals or the activation of pathways that suppress osteoblastogenesis, such as Notch. In contrast, CCN3 is known to promote chondrocyte differentiation. Given these functions, it is not surprising that CCN3 has been implicated in the progression of primary bone cancers such as osteosarcoma, Ewing’s sarcoma and chondrosarcoma. More recently, emerging evidence suggests that CCN3 may also influence the ability of metastatic cancers to colonize and grow in bone