비타민 D 식이 보충이 Ldlr-/- 마우스에서 피하·갈색 지방의 대사와 소포체 스트레스에 미치는 영향 연구 = Effects of Dietary Vitamin D supplementation on metabolism and endoplasmic reticulum stress in subcutaneous and brown adipose tissue of Ldlr-/- mice

다국어 초록 (Multilingual Abstract)

Atherosclerosis is a chronic inflammatory metabolic disease closely associated with dyslipidemia and adipose tissue dysfunction. Adipose tissue functions not only as an energy storage organ but also as an endocrine tissue that contributes to systemic inflammation and metabolic regulation. Endoplasmic reticulum (ER) stress in adipose tissue has been implicated in the progression of metabolic disorders, including atherosclerosis. Vitamin D has been suggested to modulate inflammatory and metabolic pathways. However, its tissue-specific effects in different adipose depots under atherosclerotic conditions remain unclear.
This study investigated the effects of dietary vitamin D supplementation on ER stress, inflammation, lipid metabolism, and mitochondrial-related pathways in subcutaneous adipose tissue (SAT) and brown adipose tissue (BAT) using low-density lipoprotein receptor knockout (Ldlr-/-) mice. Six-week-old male C57BL/6J mice and Ldlr-/- mice were fed either a control diet or western diet for 16 weeks and further subdivided accroding to vitamin D content (1,000 or 10,000 IU/kg diet). Body weight, adipose and organ weight, serum lipid levels, inflammatory chemokine·cytokines, lipid metabolism-related genes, beiging markers, and mitochondrial biogenesis-related genes were analyzed.
Atherosclerosis conditions significantly increased body weight, adipose tissue mass, liver weight, and serum triglyceride and total cholesterol levels. In SAT, atherosclerosis markerdly increased the expression of ER stress-related genes (Bip, Atf4, Ddit3, Xbp1 and Atf6) as well as the inflammatory chemokine Mcp1. Under atherosclerotic conditions, vitamin D supplementaion was associated with increased expression of several ER stress-related genes and Mcp1 in SAT, whereas no significant effects were observed In control mice. In contrast, BAT showed relatively limited changes in ER stess-, inflammation-, and metabolism-related gene expression when compared with SAT. Vitamin D supplementaion had no consistent effects on beiging or mitochondrial biogenesis-related gene expression in SAT and BAT.
In conclusion, dietary vitamin D exhibited tissue-specific effects on adipose tissue depending on pathological context. Subcutaneous adipose tissue was more susceptible to ER stress and inflammatory responses under atherosclerotic conditions, while brown adipose tissue displayed relative metabolic stability. These findings suggest that adipose tissue heterogeneity should be considered when interpreting the matabolic effects of vitamin D in atherosclerosis.

목차 (Table of Contents)

• I. 서론 1
• II. 문헌고찰 5
• 2. 1. 지방조직 구성과 지방세포 분화 5
• 2. 2. 지방조직의 부위별 특징 6
• 2. 3. 죽상동맥경화증과 지방조직 염증, 소포체 스트레스 9
• 2. 4. 비타민 D 11
• 2. 4. 1. 비타민 D의 기능과 대사 11
• 2. 4. 2. 비타민 D와 대사질환 및 심혈관 질환의 역학적 연관성 12
• 2. 5. 지방조직에서의 비타민 D의 역할 13
• 2. 5. 1. 지방세포의 분화와 비타민 D 13
• 2. 5. 2. 지방조직에서의 죽상동맥경화증 및 소포체 스트레스 15
• Ⅲ. 연구방법 17
• 3. 1. 실험 동물 및 식이 17
• 3. 2. 희생 및 시료 수집 20
• 3. 3. 혈청 지질 농도 측정 20
• 3. 4. RNA 추출, cDNA 합성 및 RT-qPCR 22
• 3. 5. 통계 및 분석 24
• Ⅳ. 연구결과 및 고찰 25
• 4. 1. 비타민 D 섭취에 따른 실험동물의 체중, 체중변화, 식이 섭취량,부위별 지방 조직량 및 간과 근육 조직 무게 25
• 4. 2. 혈청 지질 농도 29
• 4. 3. 피하지방 조직에서 소포체 스트레스 관련 유전자 및 염증성 케모 카인·사이토카인의 mRNA 발현 31
• 4. 4. 갈색지방 조직에서 소포체 스트레스 관련 유전자 및 염증성 케모 카인·사이토카인의 mRNA 발현 37
• 4. 5. 피하지방 조직에서 지방세포 분화 및 지질 합성, 지방산 산화 관련 유전자의 mRNA 발현 42
• 4. 6. 갈색지방 조직에서 지방세포 분화 및 지질 합성, 지방산 산화 관련 유전자의 mRNA 발현 46
• 4. 7. 간과 근육 조직에서 지방산 산화 관련 유전자의 mRNA 발현 49
• 4. 8. 피하지방 조직에서 베이지화 및 미토콘드리아 생합성 관련 유전자의 mRNA 발현 52
• 4. 9. 갈색지방 조직에서 열 생성 및 미토콘드리아 생합성 관련 유전자의 mRNA 발현 55
• Ⅴ. 요약 및 결론 57
• Ⅵ. 참고문헌 60
• ABSTRACT 77