Effects of diet, exercise and anti-obesity treatment on adult neural stem cells and neurogenesis

Jorgensen, Sara 2024. Effects of diet, exercise and anti-obesity treatment on adult neural stem cells and neurogenesis. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Obesity is a growing global health issue characterised by poor diet and reduced physical activity. Hypothalamic adult neurogenesis plays a dual role in obesity and energy homeostasis, contributing to its development through appetite and metabolic dysregulation, yet also offering a compensatory mechanism in response to over-nutrition and metabolic dysfunction. To elucidate the role of hypothalamic neurogenesis in energy homeostasis, this work determined how obesity, voluntary exercise, and anti-obesity compounds affect neural stem cells and adult-generated neurons. We used diet-induced obesity, and exposure to running wheels or anti-obesity compounds, Lipidized Prolactin Releasing Peptide (LiPrRP) and Glucagon-like Peptide-1 (GLP-1) agonists, to elucidate how they influence stem cell renewal and proliferation and neuronal differentiation and maturation in the Medial Basal Hypothalamus (MBH). In addition, we utilized the human induced Pluripotent Stem Cell-derived hypothalamic neurons to model the effects of anti-obesity compounds on human hypothalamus. Our results suggest that high fat diet initially elicits a neurogenic response, but over time reduces the survival and generation of adult-born neurons. Treatment with LiPrRP was shown to act cell-intrinsically and directly on the cell populations in the hypothalamus, potentially having long-lasting effects by prolonging the ability of the stem cell population to respond to the high fat diet, and also improving the long-term survival of adult-generated neurons. Meanwhile, exercise exhibited beneficial effects by reversing the High Fat Diet (HFD)-induced neurogenesis and by promoting long term neurogenesis in the physiological conditions. Our results provide new insights into how hypothalamic adult neurogenesis responds to physiological and pharmacological interventions. This establishes a promising foundation for future research pursuing the development of novel treatments and improved lifestyle regimens for individuals living with obesity.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	29 April 2025
Last Modified:	01 May 2025 15:07
URI:	https://orca.cardiff.ac.uk/id/eprint/177968

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