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Novel Endocrine Signaling Axis in Cardiovascular-Kidney-Metabolic Syndrome: Interactions and Therapeutic Potential of

Changlong Yang1, Lei Chen1, Hong Xiao1

  • 1Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, P.R. China.

Journal of Cellular Biochemistry
|July 28, 2026
PubMed

Insights

Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are key regulators of Cardiovascular-Kidney-Metabolic Syndrome (CKM). Understanding their interaction offers new therapeutic targets for this multisystem disorder.

Area of Science:

  • Endocrinology and Metabolism
  • Cardiovascular Research
  • Nephrology

Background:

  • Cardiovascular-Kidney-Metabolic Syndrome (CKM) is a complex multisystem disorder involving interdependent cardiovascular, renal, and metabolic dysfunctions.
  • CKM is associated with significant morbidity and mortality, often linked to conditions like type 2 diabetes and obesity.

Purpose of the Study:

  • To systematically review the biological functions and interaction mechanisms of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) in CKM.
  • To explore the roles of FGF21 and GDF15 in regulating energy metabolism, insulin sensitivity, inflammation, fibrosis, and cardiovascular protection within the CKM context.

Main Methods:

  • Systematic review of current literature on FGF21 and GDF15 in CKM.
  • Analysis of shared and distinct actions of these hormones.
  • Examination of their clinical relevance as biomarkers and therapeutic targets.

Main Results:

  • FGF21 and GDF15 emerge as central controllers of the CKM pathophysiological network.
  • These hormones influence key aspects of CKM, including metabolic regulation, inflammation, and fibrosis.
  • Their clinical relevance as biomarkers and potential therapeutic targets is highlighted.

Conclusions:

  • FGF21 and GDF15 play critical, interconnected roles in CKM.
  • Further understanding of their signaling axis is crucial for developing novel therapeutic strategies for CKM management.
  • Obstacles to clinical translation of these findings require further investigation.
Keywords:
Cardiovascular‐Kidney‐Metabolic Syndromefibroblast growth factor 21growth differentiation factor 15metabolic regulationorgan protectiontherapeutic targets

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