Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Biology

Supervisor

Staples, James F.

2nd Supervisor

Regnault, Timothy R.H.

Co-Supervisor

Abstract

Adverse in utero and postnatal conditions can increase susceptibility to metabolic syndrome (MS). Altered muscle respiration contributes to MS, but the effects of restricted oxygen and nutrients in utero on skeletal muscle mitochondria remain unknown. In this study guinea pig sows underwent uterine artery ablations mid-gestation, producing fetuses with low birth weight (LBW). Soleus muscle was collected near term or at four months of age, from LBW and control fetuses and offspring, where the offspring were fed either a Western Diet (WD) or a control diet (CD). Soleus muscles from LBW fetuses exhibit lower maximal respiration rates than normal birth weight (NBW) sham-surgery controls. Additionally, LBW/CD, NBW/WD and LBW/WD adult guinea pigs displayed reduced respiration compared with NBW/CD. Cultured C2C12 cells were utilized to better understand independent effects of hypoxia and fatty acid saturation upon cellular respiration. Both chronic (5 days) hypoxia and palmitate (16:0) reduced respiration compared with normoxia.

Summary for Lay Audience

The environment in which we develop during pregnancy can determine certain aspects of our health as adults. Previous studies have identified a correlation between low birth weight, an outcome related to intrauterine growth restriction, and the development of metabolic diseases such as type 2 diabetes and cardiovascular disease later in life. The present study aimed to identify a link between an environment low in oxygen and nutrients during pregnancy, which is observed in intrauterine growth restriction and metabolic disorders in adulthood. As there is a reduced skeletal muscle mass in cases of intrauterine growth restriction and skeletal muscle plays an important role in insulin sensing, an important contributor to metabolic health, it was chosen as the focus of this study. An intrauterine growth restricted fetal guinea pig model was used to determine a link between a poor environment during pregnancy and skeletal muscle oxygen consumption. A second study was undertaken where growth restricted animals were given either a control or Western diet to determine if a post-natal diet further affected skeletal muscle oxygen consumption. Finally, a cell culture model was used to isolate the effects of hypoxia and the common saturated fatty acid palmitate, the mono unsaturated fatty acid palmitoleate on skeletal muscle oxygen consumption. Growth restricted animals had reduced skeletal muscle oxygen consumption; however, the addition of the Western diet did not further reduce oxygen consumption but did reduce oxygen consumption in normal birth weight animals. Similarly, hypoxic cultured cells had reduced oxygen consumption and the saturated fatty acid reduced oxygen consumption of only cells cultured under normal oxygen levels. The monounsaturated fatty acid had no effect on oxygen consumption. Discovering this link allows for further studies to be conducted with potential treatments.

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