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- Title
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; Sun, Ji Su; Yang, Dong Joo; Kinyua, Ann W; Yoon, Seul Gi; Seong, Je Kyung; Kim, Juwon; Moon, Seok Jun; Shin, Dong Min; Choi, Yun-Hee; Kim, Ki Woo
- 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.
- Subjects
CILIA &; ciliary motion; HOMEOSTASIS; AUTONOMIC nervous system; HYPOTHALAMUS; BROWN adipose tissue; CELL metabolism; BONE metabolism; PROTEIN metabolism; ENERGY metabolism; PROTEINS; RESEARCH; ANIMAL experimentation; RESEARCH methodology; MEDICAL cooperation; EVALUATION research; THALAMUS; COMPARATIVE studies; CELLS; MICE
- Publication
Journal of Clinical Investigation, 2021, Vol 131, Issue 1, p1
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI138107