한빛사 논문
Dong Joo Yang a, Le Trung Tran a,b, Seul Gi Yoon c, Je Kyung Seong c,d, Dong Min Shin a, Yun-Hee Choi a, Ki Woo Kim a,b,*
a Department of Oral Biology, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea b Department of Applied Biological Science, BK21 FOUR, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea c Korea Mouse Phenotyping Center, Seoul 08826, Republic of Korea d Laboratory of Developmental Biology and Genetics, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul 08826, Republic of Korea
*Corresponding author.
Abstract
Objective
Neuronal primary cilia are known to be a required organelle for energy balance and leptin action. However, whether primary cilia directly mediate adaptive responses during starvation is yet unknown. Therefore, we investigated the counterregulatory roles of primary cilia, and their related leptin action in energy-depleted condition.
Method
We generated leptin receptor (LepR) neuron-specific primary cilia knockout (Ift88 KOLepR) mice. Leptin-mediated electrophysiological properties of the neurons in fasting condition were assessed using patch-clamp technique. Adaptive responses and neuroendocrine reflexes were measured by monitoring counterregulatory hormones.
Results
In fasting state, the leptin-induced neuronal excitability and leptin homeostasis were impaired in Ift88 KOLepR. In addition, the Ift88 KOLepR exhibited aberrant fasting responses including lesser body weight loss, decreased energy expenditure, and lower heat generation compared to wild-type littermates. Furthermore, the primary cilia in LepR neurons are necessary for counterregulatory responses and leptin-mediated neuroendocrine adaptation to starvation.
Conclusion
Our results demonstrated that the neuronal primary cilia are crucial neuronal components mediating the adaptive counterregulatory responses to starvation.
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