Developmental Programming of Obesity and Fatty Liver Disease in Offspring Exposed to Maternal Obesity and Dietary Intervention
Date
2017-12-15
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Abstract
Increased risk of developing obesity and related metabolic dysfunction has been linked to an adverse early-life environment as well as dysbiosis of gut microbiota, yet the precise molecular mechanisms involved in the establishment of disease susceptibility in offspring, and their link with the gut microbiota, remain elusive. This dissertation examines the impact of diet-induced maternal obesity on maternal metabolism and offspring susceptibility to obesity and fatty liver in a preclinical model of maternal diet-induced obesity and the potential protective effect of a maternal dietary fibre intervention. Specifically, the objectives of this thesis include 1) examining the maternal metabolic and gut microbial impact of prebiotic fibre supplementation in pregnant and lactating rats and the impact on offspring early-life obesity; 2) identifying the differences in metabolic and gut microbial adaptations to pregnancy and lactation in lean versus diet-induced obese rats; and 3) determining the potential of maternal prebiotic fibre supplementation to protect against later-life obesity and fatty liver in offspring following long-term exposure to an obesogenic diet. Our results first provide strong evidence in support of the hypothesis that maternal obesity and consumption of an obesogenic diet during pregnancy and lactation can program increased susceptibility to obesity and metabolic disease in offspring, the effects of which can be unmasked via long-term exposure to a high-fat/sucrose diet. This programming may be associated with specific shifts in maternal metabolism and gut microbial profiles. Second, we show that supplementation of a maternal high-fat/sucrose diet with the prebiotic fibre oligofructose alters maternal metabolism in a manner that attenuates early-life obesity in offspring, an outcome that is most likely mediated via prebiotic-induced shifts in the gut microbiota, in particular increased Bifidobacterium spp. abundance. Finally, we show that this supplementation attenuates the detrimental long-term programming effects of diet-induced maternal obesity, reducing hepatic steatosis and improving glucose tolerance and insulin sensitivity in adult offspring. Overall, maternal prebiotic fibre supplementation, in the context of maternal obesity, may represent an intervention during pregnancy and lactation that could help attenuate the propagation of obesity and related metabolic diseases across generations.
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Keywords
Maternal obesity, Developmental programming, Prebiotics, Metabolomics, Gut microbiota, Non-alcoholic fatty liver disease, Obesity
Citation
Paul, H. (2017). Developmental Programming of Obesity and Fatty Liver Disease in Offspring Exposed to Maternal Obesity and Dietary Intervention (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/5211