The prevalence of obesity is growing worldwide partly due to an increase in consumption of diets high in fat. Obesity is known as a risk factor for developing Alzheimer’s disease (AD) later in life. Both obesity and AD are associated with cognitive deficits and experimental high-fat diets can impair memory in cognitively normal rodents but also worsen memory deficits in AD mouse models. What is still unclear is the molecular mechanisms behind the detrimental effects of a high-fat diet on memory and if sex can influence its effect. Data in this thesis demonstrated that compared to females, male control non-transgenic (Non-Tg) mice had earlier deficits in memory after a high-fat diet that were associated with hyperinsulinemia. However, female Non-Tg mice were more vulnerable to ultrastructural changes in mitochondria morphology and loss of synapses after 6 months of a high-fat diet, changes that were similar to those observed in control-fed female triple-transgenic mice (3xTgAD). Finally, the memory deficits observed after a high-fat diet in cognitively normal mice were not associated with obesity and adiposity, as treatment with resveratrol (RSV) an anti-obesogenic compound, attenuated body weight gain and adipose tissue but failed to reverse memory impairment. In control fed 3xTgAD mice, RSV rescued memory deficits. In all experiments a high-fat diet had no detectable effect on cognitive impairment in 3xTgAD mice. In conclusion, the present thesis demonstrates that the sex-dependent differences in the effect a high-fat diet on memory are likely due to hyperinsulinemia and mitochondrial impairment and do not depend on obesity phenotype. These results demonstrate the importance of gender when studying both obesity and AD and are relevant for future clinical trials.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:677825 |
| Date | January 2015 |
| Creators | Antunes Martins, Isaura |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://www.research.manchester.ac.uk/portal/en/theses/effects-of-a-highfat-diet-in-health-and-in-alzheimers-disease-a-gender-comparison-study(318efc9c-80d9-4cee-9381-61d4ee652935).html |
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