Myostatin regulates energy homeostasis through autocrine- and paracrine-mediated microenvironment communication.

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  • Additional Information
    • Source:
      Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
    • Publication Information:
      Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
      Original Publication: New Haven [etc.] American Society for Clinical Investigation.
    • Subject Terms:
      Autocrine Communication* ; Fibroblast Growth Factors*/metabolism ; Fibroblast Growth Factors*/genetics ; Homeostasis* ; Kruppel-Like Factor 4*/metabolism ; Macrophages*/metabolism ; Mice, Knockout* ; Myostatin*/metabolism ; Myostatin*/genetics ; Paracrine Communication* ; Thermogenesis*; Animals ; Male ; Mice ; Adipocytes, Brown/metabolism ; Adipose Tissue, Brown/metabolism ; Cellular Microenvironment ; Energy Metabolism ; Kruppel-Like Transcription Factors/metabolism ; Kruppel-Like Transcription Factors/genetics
    • Abstract:
      Myostatin (MSTN) has long been recognized as a critical regulator of muscle mass. Recently, there has been increasing interest in its role in metabolism. In our study, we specifically knocked out MSTN in brown adipose tissue (BAT) from mice (MSTNΔUCP1) and found that the mice gained more weight than did controls when fed a high-fat diet, with progressive hepatosteatosis and impaired skeletal muscle activity. RNA-Seq analysis indicated signatures of mitochondrial dysfunction and inflammation in the MSTN-ablated BAT. Further studies demonstrated that Kruppel-like factor 4 (KLF4) was responsible for the metabolic phenotypes observed, whereas fibroblast growth factor 21 (FGF21) contributed to the microenvironment communication between adipocytes and macrophages induced by the loss of MSTN. Moreover, the MSTN/SMAD2/3-p38 signaling pathway mediated the expression of KLF4 and FGF21 in adipocytes. In summary, our findings suggest that brown adipocyte-derived MSTN regulated BAT thermogenesis via autocrine and paracrine effects on adipocytes or macrophages, ultimately regulating systemic energy homeostasis.
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    • Contributed Indexing:
      Keywords: Adipose tissue; Endocrinology
    • Accession Number:
      0 (fibroblast growth factor 21)
      62031-54-3 (Fibroblast Growth Factors)
      0 (Klf4 protein, mouse)
      0 (Kruppel-Like Factor 4)
      0 (Kruppel-Like Transcription Factors)
      0 (Mstn protein, mouse)
      0 (Myostatin)
    • Publication Date:
      Date Created: 20240618 Date Completed: 20240815 Latest Revision: 20240821
    • Publication Date:
      20240821
    • Accession Number:
      PMC11324308
    • Accession Number:
      10.1172/JCI178303
    • Accession Number:
      38889010