한빛사논문
- 조회1,983
Ji Su Sun1,2,#, Dong Joo Yang1,3,#, Ann W. Kinyua3, Seul Gi Yoon4, Je Kyung Seong4,5, Juwon Kim3, Seok Jun Moon1,2, Dong Min Shin1, Yun-Hee Choi1,6, and Ki Woo Kim1,2,*
1Department of Oral Biology, Yonsei University College of Dentistry, Seoul, 03722, Korea.
2Department of Applied Biological Science, BK21 FOUR, Yonsei University College of Dentistry, Seoul, 03722, Korea.
3Departments of Laboratory Medicine and Global Medical Science, Yonsei University, Wonju College of Medicine, Wonju, 26426, Korea.
4Korea Mouse Phenotyping Center, Seoul 08826, Korea.
5Laboratory of Developmental Biology and Genomics, The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
6Present Address: Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX, USA
#These authors contributed equally.
*Correspondence and reprints, materials should be addressed to: Ki Woo Kim
Departments of Oral Biology and Applied Biological Science, BK21 FOUR, Yonsei University College of Dentistry, Seoul, 03722, Korea.
Abstract
Dysfunction of primary cilia is related to dyshomeostasis, leading to a wide range of disorders. The ventromedial hypothalamus (VMH) is known to regulate several homeostatic processes, but those modulated specifically by VMH-primary cilia are not yet known. In this study, we identify VMH-primary cilia as an important organelle that maintains energy and skeletal homeostasis by modulating the autonomic nervous system. We established loss-of-function models of primary cilia in the VMH by either targeting IFT88 (IFT88 KOSF-1) using steroidogenic factor 1-Cre (SF1-Cre) or injecting an adeno-associated virus Cre (AAV-Cre) directly into the VMH. Functional impairments of VMH-primary cilia were linked to decreased sympathetic activation and central leptin resistance, which led to marked obesity and bone density accrual. Obesity was caused by hyperphagia, decreased energy expenditure, and blunted brown fat function, as well as associated with insulin and leptin resistance. The effect of bone density accrual was independent from obesity, as it was caused by the decreased sympathetic tone resulting in increased osteoblastic and decreased osteoclastic activities in the IFT88 KOSF-1 and VMH-primary cilia knock-down mice. Overall, our current study identifies VMH-primary cilia as a critical hypothalamic organelle that maintains energy and skeletal homeostasis.
논문정보
TOP52020년 후보
- Research article
- 2020년 10월 (BRIC 등록일 2020-10-27)
- 국내 연구진
- 의약학 > 응용의학
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