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Updated: Jun 4, 2025

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
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Targeting the GDF15 Signalling for Obesity Treatment: Recent Advances and Emerging Challenges

Jincheng Zhang1,2,3, Jingquan Sun2, Jielang Li1

  • 1Division of Abdominal Tumor Multimodality Treatment, Department of Medical Oncology, Cancer Center and National Clinical Research Center for Geriatrics and Laboratory of Molecular Targeted Therapy in Oncology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.

Journal of Cellular and Molecular Medicine
|December 19, 2024
PubMed

Insights

The GDF15-GFRAL pathway regulates metabolism and body weight. Targeting this pathway offers a promising obesity treatment strategy with minimal impact on muscle mass.

Area of Science:

  • Metabolic research
  • Obesity research
  • Endocrinology

Background:

  • Obesity is a global health crisis requiring novel treatments.
  • The Growth Differentiation Factor 15 (GDF15)-Glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL) pathway is integral to metabolic regulation.
  • Preserving skeletal muscle mass during weight loss is critical.

Purpose of the Study:

  • To review the regulation, distribution, and metabolic roles of the GDF15-GFRAL axis.
  • To explore the potential of targeting the GDF15-GFRAL pathway for obesity treatment.
  • To discuss recent advancements and challenges in GDF15-GFRAL-targeted obesity therapies.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Analysis of GDF15-GFRAL pathway mechanisms.
  • Exploration of therapeutic strategies targeting the GDF15-GFRAL axis.

Main Results:

  • The GDF15-GFRAL pathway significantly influences appetite and body weight.
  • Targeting this pathway shows promise for obesity treatment.
  • This approach may preserve skeletal muscle mass during weight reduction.

Conclusions:

  • The GDF15-GFRAL axis is a key regulator of energy homeostasis.
  • Targeting the GDF15-GFRAL pathway presents a viable strategy for combating obesity.
  • Further research is needed to overcome challenges in clinical application.
Keywords:
GDF15GFRALappetite suppressionenergy metabolismobesityweight loss

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