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Title: The effect of diet-induced maternal obesity on offspring energy balance in a murine model and the therapeutic potential of a maternal dietary intervention with a fibre supplement
Author: Maragkoudaki, Xanthi
ISNI:       0000 0004 5368 1911
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2014
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Introduction: Obesity now affects nearly 1 in 3 adults in the UK. It is estimated that 20% of pregnant women are obese. Increasing evidence associate obesity in pregnancy with susceptibility to obesity and metabolic syndrome in the child. Here an established mouse model of maternal obesity was employed to investigate energy balance and glucose metabolism in the offspring. Polydextrose (PDX) has been shown to improve glucose metabolism and, therefore may be beneficial in obese pregnancy. Hypothesis: It was hypothesised that (a) maternal obesity has adverse effects on offspring energy balance and glucose metabolism and that (b) these adverse effects will be prevented by supplementation of the maternal diet with PDX during pregnancy and lactation. Moreover, it was investigated whether PDX supplementation in obese pregnancy is protective against the adverse influences of an obesogenic dietary exposure in adulthood. Methods: Female mice were fed a control or an obesogenic diet, 6-weeks before mating and throughout pregnancy and lactation. A cohort of the obese dams was assigned to supplementation with 5% PDX in pregnancy and lactation. Maternal profiles were assessed during pregnancy. At 3 and 6-months of age offspring energy intake (EI), energy expenditure (EE) and Respiratory Exchange Ratio (RER) were measured by indirect calorimetry and glucose-tolerance-tests were performed. At 3-months the animals were challenged for 3-weeks with an obesogenic diet before re-estimation of EI, EE, and RER. Microbiota composition, mitochondria copy number and UCP gene expression was assessed as potential underlying mechanisms. Results: Maternal supplementation with PDX improved reproductive success, increased water intake and decreased markers of inflammation during gestation in the dams. At 3 months of age, offspring of obese dams (OffOb) metabolic parameters did not differ from offspring of control dams (OffCon). At 6 months OffOb were heavier (P<0.01), had lower RER (P<0.05) and lower EE (P<0.001) compared to OffCon. OffOb had impaired glucose metabolism compared to OffCon (P<0.05). Maternal supplementation with PDX prevented these defects. Following 3-weeks obesogenic dietary challenge OffObs demonstrated hyperphagia, decreased EE (P<0.05) and subsequently greater weight gain compared to controls (P<0.05), which were prevented by maternal PDX supplementation. Maternal obesity resulted in decreased mitochondria copy number at 30 days of age and altered microbiota composition at 6 months of age, which may mediate the changes observed later in life. Maternal supplementation with PDX, prevented mitochondrial dysfunction, increased the number of beneficial microbiota and the expression of UCP1 and 3 genes. Conclusions: Maternal obesity adversely influences offspring energy balance, which is prevented by maternal intervention with PDX. PDX may, therefore, provide a potential therapeutic intervention in preventing the transgenerational acceleration of obesity.
Supervisor: Taylor, Paul David ; Poston, Lucilla Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available