Medicine and Health Sciences Commons^™

Free Fatty Acid Treatment Alters Autophagy During Mouse Preimplantation Embryo Development, Zuleika C. L. Leung

Electronic Thesis and Dissertation Repository

Obesity-induced hyperlipidemia is one of the main factors for female infertility. Hyperlipidemia, specifically with high levels of palmitic acid (PA) and oleic acid (OA), interferes with preimplantation development. Autophagy is essential in early embryo development but, it is unknown whether hyperlipidemia affects autophagic mechanisms in preimplantation embryos. It was hypothesized that PA will alter autophagy in preimplantation mouse embryos and that the subsequent effects will be reversed by OA. PA impaired blastocyst development by arresting embryos at the 8-cell stage. PA also elevated early embryo autophagy by increasing autophagosome formation, decreasing maturation, and disrupting degradation. Co-treatment with OA showed developmental …

Investigating Pathways Associated With Intervertebral Disc Degeneration And Back Pain., Geoffrey J. Kerr

Electronic Thesis and Dissertation Repository

Lower back pain (LBP) is one of the most common conditions worldwide, yet, current therapeutics are limited to symptomatic relief and do not directly treat the underlying cause of pain. This is largely due to an incomplete understanding of the biological pathways and tissues involved in LBP. While many tissues appear to be involved, intervertebral disc (IVD) degeneration is believed to be a major contributor.

The main aim of this thesis was to characterize the role of two environmental risk factors, mechanical loading and obesity, in the initiation of IVD degeneration and associated pain using the mouse as a preclinical …

Inhibition Of Elongation Factor 1a-1 Activity And Hepatic Lipotoxicity, Alexandra Margaret Anne Hetherington

Electronic Thesis and Dissertation Repository

Elongation factor 1A-1 (eEF1A-1) was previously identified as a mediator of fatty acid-induced cell death (lipotoxicity) downstream of endoplasmic reticulum (ER) stress. Furthermore, inhibition of the peptide elongation activity of eEF1A-1 with the cyclic depsipeptide didemnin B (DB) diminishes ER stress and lipotoxicity in cultured hepatocytes. Since ER stress is involved in nonalcoholic fatty liver disease (NAFLD), it was hypothesized that administration of DB to obese mice with NAFLD would reduce hepatic lipotoxicity. Treatment with DB for one week improved several parameters associated with hepatic lipotoxicity and modestly decreased food intake without evidence of illness. Liver triglycerides and protein markers …

Modulation Of The Cardiomyocyte Hypertrophic Responses To Endothelin-1 By Adipocytes, Suresh Chandra Bairwa

Electronic Thesis and Dissertation Repository

Leptin and adiponectin are the adipokines that are shown to exert pro-hypertrophic and anti-hypertrophic effects respectively, in cardiomyocytes. We sought to determine the direct interaction between the adipocytes and cardiomyocytes during endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy and determine the role of leptin and adiponectin.

The adipose tissue conditioned medium (ACM) inhibited the ET-1-induced hypertrophy in a concentration-dependent manner and this anti-hypertrophic effect was more potent or reversed in the presence of leptin receptor antagonist (LRA; 0.1 nM) or adiponectin receptor-1 antibody (ARA; 100 ng/mL), respectively. ACM from heart failure rats induced by coronary artery ligation or obese rats did not mitigate …

Fully Automated Segmentation And Quantification Of Abdominal Adipose Tissue Compartments In Mouse Mri, Colin M. Mccurdy

Electronic Thesis and Dissertation Repository

Obesity currently affects 25% of Canadians and is strongly associated with many diseases including diabetes, cardiovascular disease, and cancer. However, only Intra-Abdominal Adipose Tissue (IAAT) is an important predictor of obesity associated disease and mortality. Magnetic Resonance Imaging (MRI) is an effective modality for imaging fat and methods have been developed to automate segmentation of IAAT. Currently existing techniques for automated segmentation in mice require acquisition using high magnetic field MRI equipment and use image acquisition techniques with low precision for fat quantification. We demonstrate a new fully automated technique for fat quantification in clinical strength mouse MRI through adaptation …

Fetal And Neonatal Exposure To Nicotine Augments Hepatic Fatty Acid Synthesis In Rat Offspring Long-Term, Noelle L. Ma

Electronic Thesis and Dissertation Repository

While nicotine replacement therapy (NRT) is presumed to be a safer alternative to smoking in pregnancy, the long-term consequences in offspring are still largely unknown. Animal studies now suggest that maternal nicotine exposure during pregnancy and lactation (MNE-PL) leads to a wide variety of adverse outcomes for the offspring, including increased adiposity. The focus of this study was to investigate how MNE-PL in rats may lead to liver dysfunction long-term in offspring through alterations in gene expression and epigenetic modifications. Postnatal day 180 (PND180) offspring exposed to nicotine during pregnancy and lactation (1mg/kg/day) exhibited increased circulating and hepatic triglycerides concomitant …