Ventromedial hypothalamic primary cilia control energy and skeletal homeostasis
| Autor: | Ji Su Sun, Yun Hee Choi, Dong Joo Yang, Je Kyung Seong, Ki Woo Kim, Seok Jun Moon, Ann W. Kinyua, Seul Gi Yoon, Juwon Kim, Dong Min Shin |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Bone density medicine.medical_treatment Biology Bone and Bones Mice 03 medical and health sciences 0302 clinical medicine Internal medicine Organelle medicine Animals Homeostasis Cilia Mice Knockout Ventral Thalamic Nuclei Tumor Suppressor Proteins Cilium Leptin Insulin General Medicine Autonomic nervous system 030104 developmental biology Endocrinology Hypothalamus 030220 oncology & carcinogenesis Energy Metabolism Research Article |
| Zdroj: | J Clin Invest |
| ISSN: | 1558-8238 0021-9738 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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