Primary cilia regulate adaptive responses to fasting

Dong Joo Yang, Le Trung Tran, Seul Gi Yoon, Je Kyung Seong, Dong Min Shin, Yun Hee Choi, Ki Woo Kim

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number155273
JournalMetabolism: Clinical and Experimental
Volume135
DOIs
Publication statusPublished - 2022 Oct

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea ( 2022R1C1C2010320 for D.J.Y.; 2021R1I1A1A01049540 for Y.-H.C.; 2021R1A2C4002011 and 2016R1A5A2008630 for K.W.K.).

Publisher Copyright:
© 2022 The Authors

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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