Year of Publication
Doctor of Philosophy (Medical Science)
Dr. Kevin J. Pearson
Dr. Lisa Cassis
Recent advancements have uncovered environmental contributions to obesity and diabetes etiology. In fact, perinatal malnutrition resulting in low birth weight (LBW) has been shown to correlate with later life obesity and impaired glucose tolerance in aged offspring. LBW can result from a myriad of developmental perturbations including macronutrient restriction, hypoxia, maternal stress and toxin exposure.
Polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants that bioaccumulate in the food chain resulting in dietary exposure in humans. Maternal and cord blood PCB levels are inversely associated with birth weight, and recent studies indicate that perinatal exposures to PCBs contribute to gender-specific obesity development in children. PCBs have also been shown to enter breast milk resulting in direct exposure in early postnatal life. Therefore, we hypothesized that perinatal PCB exposure cause developmental blight resulting in decreased birth weight and increased adiposity and glucose intolerance with aging. We found that mice perinatally exposed to PCBs did not differ in birth weight, but exhibited sex-specific effects on adiposity. Females perinatally exposed to PCBs were significantly more obese at 7 weeks of age while male offspring exhibited no difference in fat mass but had decreased lean mass compared to controls. With aging, the differences in females dissipated while the male offspring decreased lean mass persisted. Male offspring perinatally exposed to PCBs displayed impaired glucose tolerance at 7 weeks of age but normalized over time, while the females were glucose intolerant only after 6 months of age. This impairment of glucose tolerance was not attributed to insulin resistance. These data illustrate time-dependent and sex-specific perturbations of maternal PCB exposure on offspring body composition and glucose homeostasis.
As the liver is a major facilitator in glucose homeostasis and xenobiotic detoxification, we investigated PCB-induced alterations in hepatic gene expression and found attenuated expression of glycolytic genes and increased expression of detoxifying and antioxidant genes in both PCB-exposed maternal and offspring livers. Taken together, these data demonstrate a role for perinatal pollutant exposure in the etiology of glucose intolerance. Further studies are required to elucidate the mechanisms causing sex-specific modulation of body composition and glucose intolerance.
Rashid, Cetewayo S., "AN INVESTIGATION OF PERINATAL POLYCHLORINATED BIPHENYL EXPOSURE ON BODY COMPOSITION AND GLUCOSE HOMEOSTASIS" (2013). Theses and Dissertations--Nutritional Sciences. 9.