The combined effects of plant polyphenols and fatty acids on protective cellular mechanisms associated with molecular perturbations of obesity and neurotoxicity

Joyce, Ellen ORCID: https://orcid.org/0000-0002-2595-2898 (2023) The combined effects of plant polyphenols and fatty acids on protective cellular mechanisms associated with molecular perturbations of obesity and neurotoxicity. PhD thesis, University of Worcester.

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Text (Doctor of Philosophy (PhD) in Biochemistry) ELLEN JOYCE THESIS - March 2023.pdf - Submitted Version Download (13MB) | Preview

Abstract

A high-fat diet (HFD), typical of a “western-style” diet (WSD), is rich in lipids such as saturated fatty acids (SFA) and cholesterol and is associated with an increased risk of developing metabolic disorders, obesity and diabetes, cognitive impairment, anxiety, stress, and depression. Ginkgo biloba (GbE) has been shown to possess antioxidant, anti-inflammatory, and anti-obesogenic properties as well as neurological protection. GbE has been shown to reduce visceral adiposity, weight gain and food intake. In this study, male Wistar rats were fed either a normal fat diet (NFD) or HFD for 2 months to induce obesity. HFD-induced obese rats were then treated for 14 days with either GbE, saline or were calorically restricted. Retroperitoneal and mesenteric adipose tissues, liver, hippocampus, and hypothalamus tissues were analysed for total fatty acids, triglycerides, cholesteryl esters, monoglycerides, diglycerides and phospholipids profiles analysed by gas chromatography flame ionisation detection. A PC12 neuronal cell model was also established for in-house in vitro studies undergoing GbE, NFD and/or HFD treatment.

Key findings include that in all tissues except hippocampus and hypothalamus, a HFD increased SFA and decreased monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) in total fatty acid profiles. More dynamic changes occurred across the cholesteryl esters, monoglycerides and diglycerides. Phospholipid profiles showed the most changes with GbE treatment. In PC12 neuronal cell treatment, HFD FA treatment increased Akt activation and neurofilament-L protein expression levels compared to NFD treatment. NFD treatment partially ameliorated decreased Nrf2 protein expression following hydrogen peroxide-induced oxidative stress while HFD treatment did not. GbE treatment increased levels of oleic acid and mead acid in PC12 cells. Future work would include longer treatment times, investigating other tissues and proteome analysis of tissues.

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