Date of Award

12-2023

Document Type

Thesis

Degree Name

Master of Science (MS)

Program

Biomedical Sciences

Track

Microbiology, Immunology, and Biochemistry

Research Advisor

Amandeep Bajwa, PhD

Committee

Stephen Alway, PhD; Zheng Fan, PhD

Keywords

Adipose tissue;IL-6;Metabolic disorder;Mitochondria;Mitochondrial transfer;Obesity

Abstract

Obesity, a global health epidemic, poses significant challenges to public well-being due to its complex interplay of metabolic dysregulation, inflammation, and associated comorbidities. Mitochondria, central to ATP production, lipid metabolism, and thermogenesis, play a crucial role in modulating white adipose tissue metabolism. This thesis explores an innovative strategy for addressing mitochondrial dysfunction in obesity which is a critical aspect of this multifactorial problem. The research findings presented herein uncover the impact of introducing exogenous mitochondria into NIH3T3-L1 adipocytes on various aspects of adipocyte function. The key discoveries of this study include a remarkable upregulation of energy expenditure genes, notably Ucp1, Dio2, Ppara, and Ppargc1a, upon exposure to exogenous mitochondria, thereby promoting a favorable shift in metabolic profiles within white adipocytes. Mitochondria therapy also appeared to stimulate mitochondrial biogenesis through an increase in Ppara and Ppargc1a expression. Mitochondrial therapy also led to reduced lipid content, indicating a potential means to mitigate adipocyte hypertrophy. Additionally, the release of free fatty acids and glycerol was elevated, reflecting enhanced lipolysis. Thus, this approach showed significant potential for improving energy expenditure and oxidative capacity within adipocytes. Surprisingly, mitochondrial therapy resulted in increased IL-6 levels, contradicting earlier studies showing IL-6 reduction in other injury models. The role of IL-6 in adipose tissue metabolism and obesity has been extensively studied, and this research suggests a possible link between the observed beneficial effects of mitochondria therapy and IL-6 signaling. To test this hypothesis, the study examined the impact of IL-6 neutralization on the metabolic benefits mediated by mitochondrial therapy. Neutralizing IL-6 led to a substantial decrease in the expression of genes associated with energy expenditure, oxidative capacity, and lipid metabolism. This effect highlights the significance of IL-6 in the mechanism of action of mitochondria therapy. In summary, this thesis offers insights into the potential therapeutic implications of mitochondrial transfer in addressing obesity-related metabolic dysregulation. By elucidating specific mechanisms, it contributes to the development of clinically safe treatment options in the ongoing battle against obesity. .

Declaration of Authorship

Declaration of Authorship is included in the supplemental files.

ORCID

0009-0006-1137-849X

DOI

10.21007/etd.cghs.2023.0652

Additional Files
2023-037-Masudar-DOA.pdf (202 kB)
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