Full metadata record
DC Field | Value | Language |
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dc.contributor.advisor | Park, Jiyoung | - |
dc.contributor.author | Oh, Jiyoung | - |
dc.date.accessioned | 2024-04-11T15:19:08Z | - |
dc.date.available | 2024-04-11T15:19:08Z | - |
dc.date.issued | 2024-02 | - |
dc.description.abstract | Extracellular matrix (ECM) surrounded by adipose tissue (AT) such as collagen, elastin, and fibronectin helps regulate the formation AT structure, including construction of scaffolds, basal membrane, and microfibrils. Type 6 collagen (Col6) is one of the major components of AT ECM, which is intracellularly assembled into heterotrimers with three chains Col6a1, a2, a3, followed by secretion into the extracellular space, forming mature microfibrils. After secretion, the C5 domain of Col6a3 is proteolytically cleaved by matrix metalloproteinases (MMPs), which is called endotrophin. However, it remains underappreciated that ECM is critical in AT biology and a detailed mechanism of the impacts of ECM on adipocyte function has not been clearly uncovered. So, I aimed to elucidate the role of each Col6 chain and its cleaved protein endotrophin in adipocyte function. In the first part of this study, I elucidated the role of each col6 chain in adipocyte functions such as adipogenesis and lipolysis. Specifically, Each Col6 chain cooperatively forms Col6 microfibrils, which is important for adipogenesis, involved with p38 activation. And independently, Col6a3 plays an important role in maintaining lipolytic capacity in adipocytes in normal lean condition, and its cleavage protein endotrophin increased basal adipocyte lipolysis partially through IL-6 mediated inflammation. Obesity has been a worldwide health problem caused by energy imbalance which occurs when food intake excesses energy expenditure by physical inactivity or poor diets. Obesity is associated with a variety of metabolic dysfunction including fibro-inflammation and insulin resistance. In obesity, the levels of Col6 are elevated in AT. However, the mechanistic insight of adipocyte-derived ECM components in obesity remains elusive. So, I aimed to elucidate the distinctive role of Col6a3 and its cleavage protein endotrophin in the pathological condition such as obesity. In the second part of this study, I revealed that endotrophin plays a role as a significant contributor to adipocyte dysfunction in obesity. In obesity, Col6a3 deficiency protects metabolic stress-induced insulin resistance and its cleavage protein endotrophin facilitates adipocyte lipolysis, inflammation, and apoptosis leading to the development of insulin resistance, partially through JNK signaling pathway. Increased intracellular endotrophin levels have been frequently detected within AT in obese or diabetic conditions, which means that endotrophin is associated with obesity-related pathologies. However, how endotrophin intracellularly trafficks and influences metabolic homeostasis in adipocyte remain elusive. Therefore, I aimed to investigate the intracellular trafficking of endotrophin and its metabolic effects in adipocytes depending on lean or obese condition. In the last part of this study, I addressed that distinctive trafficking of intracellular endotrophin in adipocytes in obesity compared to lean control is associated with autophagosome formation through mediating supply of COPII vesicles to autophagosomes. Therefore, accumulation of intracellular endotrophin inside the adipocyte plays a crucial role in disturbing autophagic flux contributing to metabolic dysfunction in obesity. Taken together, this study demonstrated the detailed role of endotrophin in the development of obesity-related metabolic disease. Furthermore, this study strongly suggests that intracellular endotrophin accumulation can be a biomarker for ECM homeostasis imbalance and targeting excessive endotrophin can be a promising therapeutic strategy for treating obesity and its related metabolic diseases. | - |
dc.description.degree | Doctor | - |
dc.description | Department of Biological Sciences | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/82049 | - |
dc.identifier.uri | http://unist.dcollection.net/common/orgView/200000743225 | - |
dc.language | ENG | - |
dc.publisher | Ulsan National Institute of Science and Technology | - |
dc.rights.embargoReleaseDate | 9999-12-31 | - |
dc.rights.embargoReleaseTerms | 9999-12-31 | - |
dc.title | Deciphering the role of endotrophin in adipocyte function: implications for obesity-related metabolic disease | - |
dc.type | Thesis | - |
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