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Ventromedial hypothalamic primary cilia control energy and skeletal homeostasis

Authors
 Ji Su Sun  ;  Dong Joo Yang  ;  Ann W Kinyua  ;  Seul Gi Yoon  ;  Je Kyung Seong  ;  Juwon Kim  ;  Seok Jun Moon  ;  Dong Min Shin  ;  Yun-Hee Choi  ;  Ki Woo Kim 
Citation
 JOURNAL OF CLINICAL INVESTIGATION, Vol.131(1) : e138107, 2021-01 
Journal Title
 JOURNAL OF CLINICAL INVESTIGATION 
ISSN
 0021-9738 
Issue Date
2021-01
Keywords
Endocrinology ; Homeostasis ; Leptin ; Metabolism ; Obesity
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 (SF-1-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 and was also associated with insulin and leptin resistance. The effect of bone-density accrual was independent of obesity, as it was caused by decreased sympathetic tone resulting in increased osteoblastic and decreased osteoclastic activities in the IFT88-KOSF-1 and VMH primary cilia knockdown mice. Overall, our current study identifies VMH primary cilia as a critical hypothalamic organelle that maintains energy and skeletal homeostasis.
Files in This Item:
T202100333.pdf Download
DOI
10.1172/JCI138107
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ki Woo(김기우) ORCID logo https://orcid.org/0000-0002-7790-1515
Moon, Seok Jun(문석준) ORCID logo https://orcid.org/0000-0001-7282-2888
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182060
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