Full metadata record
DC Field | Value | Language |
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dc.contributor.advisor | 김은경 | - |
dc.contributor.author | Dayoung Kwon | - |
dc.date.accessioned | 2023-03-22T19:56:33Z | - |
dc.date.available | 2023-03-22T19:56:33Z | - |
dc.date.issued | 2023 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/45698 | - |
dc.identifier.uri | http://dgist.dcollection.net/common/orgView/200000657501 | - |
dc.description | autophagy, tanycytes, glucose starvation, fatty acids, palmitate | - |
dc.description.abstract | Autophagy is the catabolic process of unnecessary cellular components or dysfunctional organelles via lysosomal degradation by itself for the maintenance of cellular homeostasis. Emerging evidence shows that autophagy in neuronal and glial cells plays a key role in regulating appetite and energy balance. Tanycytes, specialized ependymal cells, surround the 3rd ventricle and participate in the control of energy balance by detecting metabolic signals such as nutrients and hormones in the bloodstream or the cerebrospinal fluid. However, the metabolic regulation within tanycytes in response to nutrient signals has not been fully elucidated. Herein, considering the unique position of tanycytes facing the nutrient circulation, I investigated the levels of autophagy induced by glucose starvation and treatment of different types of fatty acids, namely, palmitate, stearate, and linoleate in mouse tanycyte-like cell line A2/29. Pharmacological or genetic inhibition of autophagy and fluorescence imaging of autophagy flux confirmed autophagy induced by glucose starvation and palmitate treatment. Interestingly, glucose starvation stimulated the activity of AMPK which regulates ULK1 and Raptor, whereas palmitate phosphorylated ULK1 and Raptor without the activation of AMPK. Tanycyte-specific Atg7 deficient mice fed a high-fat diet (HFD) showed significant increases in body weight and food intake compared to control mice fed HFD. These results suggest that nutrient signals such as glucose and fatty acids regulate autophagy in tanycytes, influencing energy metabolism. | - |
dc.description.abstract | 자가포식(autophagy)은 세포 항상성을 유지하기 위해 일어나는 리소좀 분해를 통한 불필요한 세포 구성 요소 또는 제대로 기능하지 못하는 세포 소기관의 자체적 이화 과정을 의미한다. 새로운 증거들은 신경세포 및 신경교세포의 자가포식이 식욕과 에너지 균형을 조절하는 데 중요한 역할을 한다는 것을 보여준다. 띠뇌실막세포(tanycytes)는 제3뇌실을 둘러싸고 있는 특수 뇌실막세포로, 혈류나 뇌척수액에서 영양소와 호르몬 등의 대사적 신호를 감지함으로써 에너지 균형의 조절에 참여한다. 그러나, 영양 신호에 의해 일어나는 띠뇌실막세포 내 대사조절은 완전히 밝혀지지 않았다. 본 논문에서는, 영양소의 순환에 직접 접하고 있는 띠뇌실막세포의 독특한 위치를 고려하여, 마우스 띠뇌실막세포 유사 세포주 A2/29에서 포도당 결핍 및 팔미트산, 스테아르산, 그리고 리놀레산을 이용하여 여러가지 지방산들의 처리에 의해 유도되는 자가포식을 조사하였다. 자가포식의 약리학적 또는 유전적 억제와 자가포식 흐름의 형광 이미징은 포도당 결핍과 팔미트산에 의해 유도된 자가포식을 확인하였다. 흥미롭게도, 포도당 결핍은 ULK1과 Raptor를 조절하는 AMPK의 활성을 자극하지만, 반면에 팔미트산은 AMPK의 활성화 없이 ULK1과 Raptor를 인산화하였다. 또한 고지방 식이(HFD)를 먹인 띠뇌실막세포-특이적Atg7 결핍 마우스는 고지방 식이를 먹인 대조군 마우스에 비해 체중과 음식 섭취에서 유의미한 증가를 보였다. 이러한 결과는 포도당과 지방산과 같은 영양 신호가 띠뇌실막세포의 자가포식을 조절하여, 에너지 대사에 영향을 미칠 수 있음을 시사한다. | - |
dc.description.tableofcontents | Ⅰ. Introduction 1 Ⅱ. Materials and methods 8 1. Mice 8 2. Cell culture 8 3. Preparation of fatty acids 9 4. Antibodies and chemical reagents 9 5. Genotyping 9 6. Cell viability assay 10 7. siRNA and plasmid transfection 11 8. Western blotting 11 9. Fluorescence microscopy 12 10. Quantitative real-time PCR 12 11. Statistical analysis 13 Ⅲ. Results 14 1. Glucose starvation exerts a cytotoxic effect in mouse tanycyte-like cell line A2/29 in a time-dependent manner. 14 2. Glucose starvation induces autophagy in tanycyte-like cells. 16 3. Glucose starvation stimulates autophagy flux in tanycyte-like cells. 19 4. Glucose starvation leads to changes in the activation of autophagy regulators AMPK, ULK1, and Raptor. 19 5. Palmitate, stearate, and linoleate have cytotoxicity in tanycyte-like cells in a dose-dependent manner. 22 6. Palmitate and stearate increase the levels of the autophagy marker in tanycyte-like cells. 24 7. Palmitate activates autophagy in tanycyte-like cells in a dose-dependent manner. 24 8. Stearate impairs autophagy in tanycyte-like cells. 25 9. Autophagy flux is enhanced by palmitate but impaired by stearate in tanycyte-like cells. 29 10. Palmitate alters the activation of ULK1 and Raptor except for AMPK in tanycyte-like cells. 29 11. Ablation of autophagy in tanycytes exacerbates diet-induced obesity in vivo. 32 Ⅳ. Discussion 36 Ⅴ. Conclusion 39 Ⅵ. References 40 Abstract in Korean 44 |
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dc.format.extent | 44 | - |
dc.language | eng | - |
dc.publisher | DGIST | - |
dc.title | Roles of glucose and fatty acids in the regulation of autophagy in hypothalamic tanycytes | - |
dc.title.alternative | 시상하부 띠뇌실막세포 자가포식작용 조절에서의 포도당과 지방산의 역할 | - |
dc.type | Thesis | - |
dc.identifier.doi | 10.22677/THESIS.200000657501 | - |
dc.description.degree | Master | - |
dc.contributor.department | Department of Brain Sciences | - |
dc.contributor.coadvisor | Byung-Hoon Lee | - |
dc.date.awarded | 2023-02-01 | - |
dc.publisher.location | Daegu | - |
dc.description.database | dCollection | - |
dc.citation | XT.BM 권22 202302 | - |
dc.date.accepted | 2023-03-21 | - |
dc.contributor.alternativeDepartment | 뇌과학과 | - |
dc.subject.keyword | autophagy | - |
dc.subject.keyword | tanycytes | - |
dc.subject.keyword | glucose starvation | - |
dc.subject.keyword | fatty acids | - |
dc.subject.keyword | palmitate | - |
dc.contributor.affiliatedAuthor | Dayoung Kwon | - |
dc.contributor.affiliatedAuthor | Eun-Kyoung Kim | - |
dc.contributor.affiliatedAuthor | Byung-Hoon Lee | - |
dc.contributor.alternativeName | 권다영 | - |
dc.contributor.alternativeName | Eun-Kyoung Kim | - |
dc.contributor.alternativeName | 이병훈 | - |
dc.rights.embargoReleaseDate | 2028-02-28 | - |
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