Neural regulation of energy and bone homeostasis by the synaptic adhesion molecule Calsyntenin-3

Sung Jin Kim, Yong Taek Jeong, Se Rok Jeong, Munsu Park, Hye Sun Go, Mi Young Kim, Je Kyung Seong, Ki Woo Kim, Jeong Taeg Seo, Chul Hoon Kim, Ji Hyun Lee, Seok Jun Moon

    Research output: Contribution to journalArticlepeer-review

    7 Citations (Scopus)

    Abstract

    Neuronal regulation of energy and bone metabolism is important for body homeostasis. Many studies have emphasized the importance of synaptic adhesion molecules in the formation of synapses, but their roles in physiology still await further characterization. Here, we found that the synaptic adhesion molecule Calsyntenin-3 (CLSTN3) regulates energy and bone homeostasis. Clstn3 global knockout mice show reduced body mass with improved leptin sensitivity and increased energy expenditure compared to their wild-type littermates. In addition, Clstn3 knockout mice show reduced marrow volume and cortical bone mass without alteration of trabecular bone microarchitecture. This reduced bone mass is not bone cell-autonomous because neither osteoblast- nor osteoclast-specific Clstn3 knockout mice show bone defects; similarly, in vitro cultures of both Clstn3 knockout osteoblasts and osteoclasts do not show any defects. These reduced body and bone mass phenotypes can be attributed instead to neuronal CLSTN3 because they are recapitulated by pan-neuronal but not sympathetic neuron-specific deletion of Clstn3. This study reveals novel physiological functions of neuronal Clstn3 as a key regulator of energy and bone homeostasis.

    Original languageEnglish
    Pages (from-to)793-803
    Number of pages11
    JournalExperimental and Molecular Medicine
    Volume52
    Issue number5
    DOIs
    Publication statusPublished - 2020 May 1

    Bibliographical note

    Publisher Copyright:
    © 2020, The Author(s).

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Clinical Biochemistry

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