이전|다음

사회적 시차는 순환 프로락틴 리듬 장애를 매개로 한 간 지질 대사의 일주기 재구성을 통해 지방간을 유발한다

  • role： Contribute equally, First author同等贡献者, 第一作者
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

Peng-Zi Zhang12,  
  • role： Contribute equally同等贡献者
  • Affiliation：

    National Key Laboratory for Novel Software Technology and the National Institute of Healthcare Data Science, Nanjing University, Nanjing 210008, China

Ying-Huan Shi3,  
  • role： Contribute equally同等贡献者
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

Yu-Xin Guo12,  
  • role： Contribute equally同等贡献者
  • Affiliation：

    National Key Laboratory for Novel Software Technology and the National Institute of Healthcare Data Science, Nanjing University, Nanjing 210008, China

Ya-Yuan Li3,  
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

Hong-Li Yin12,  
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

Tian-Yu Wu12,  
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

Ye Zhu12,  
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

Jia-Xuan Jiang12,  
  • role： Corresponding author通信作者
  • Affiliation：

    Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

    Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing 210008, China

  • Email：biyan@nju.edu.cn
  • Introduction：* Yan Bi biyan@nju.edu.cn
Yan Bi12*

추상적인

배경 일주기 불일치, 특히 사회적 시차(SJL)의 유병률은 대사 장애 유행에 크게 기여합니다. 그러나 SJL이 간에 미치는 정확한 영향은 잘 밝혀지지 않았습니다. 방법 SJL 환자와 SJL 상태의 생쥐에서 순환 프로락틴(PRL)의 리듬성을 평가했습니다. 야행성 모델을 사용하여 야행성이 야행성 모델을 사용하여 야행성 모델에서 야행성을 탐구했습니다. 야행성 모델에서 야행성 모델에서 야행성 모델에서 야행성 모델에서 야행성 모델에서 야행성 모델에서 야행성 모델에서 야행성 모델에서 야행성을 탐구했습니다. 루시퍼레이스 리포터 분석, 전기영동 이동성 이동 분석, 크로마틴 면역 침강 분석을 통해 PRL에 대한 레티노산 수용체 관련 고아 수용체 α의 전사 기전을 연구했습니다. 인간과 생쥐 간에서의 RNA-seq 및 일주기 분석을 통해 SJL 관련 비동기 PRL이 간지질 대사에 미치는 메커니즘을 연구했습니다. 서로 다른 시점에서 SJL 유도 생쥐에 대한 PRL 개입의 치료 효과를 비교했습니다. 결과 SJL은 혈청 PRL 리듬성 장애를 매개로 하는 대사 기능 장애 관련 지방간 질환(MASLD)의 위험을 증가시킵니다. 특히 SJL은 뇌하수체에서 PRL의 리듬 전사를 억제하여 순환 내에서 비동기화된 PRL 수준을 초래합니다. 제트랙 조건에서 간 PRL 신호 경로의 리듬성이 현저히 감소하여 간의 미토겐 활성화 단백질 키나아제/사이클린 D1 발현 억제를 통한 지질 합성이 증가했습니다. 주목할 점은 제트랙된 생쥐에서 PRL 최저점에서 PRL 치료가 기존 PRL 투여에 비해 간 지방 함량 및 간 손상 지표를 더 크게 감소시켰다는 것입니다. 결론 재프로그램된 간 PRL 신호 경로와 동반된 지질 대사 항상성 이상이 SJL 하에서 지방간의 원인 메커니즘이며, 이는 혈청 PRL 리듬의 교란을 통해 매개됩니다. PRL 리듬 복원은 SJL로 유발된 지방간을 효과적으로 완화할 수 있어 MASLD 치료에 대한 새로운 통찰을 제공합니다.

키워드

사회적 시차;프로락틴;일주기 리듬;대사 장애 관련 지방간 질환 (MASLD)

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