Emerging Roles of GDF15 in Metabolic and Cardiovascular Diseases

Area of Science:

• Endocrinology and Metabolism
• Molecular Biology
• Cellular Signaling

Background:

• Growth Differentiation Factor 15 (GDF15) is a stress-responsive cytokine within the TGF-β superfamily.
• It plays a significant role in regulating metabolism and inflammation.
• GFRAL is identified as the central receptor mediating GDF15's effects.

Purpose of the Study:

• To provide a comprehensive review of GDF15's expression, regulation, and function.
• To synthesize evidence linking GDF15 to various metabolic diseases and aging.
• To evaluate current GDF15-targeted drug development and identify future research directions.

Main Methods:

• Literature review and synthesis of existing research on GDF15.
• Analysis of regulatory networks and interactions with other metabolic factors.
• Evaluation of therapeutic strategies and drug development for GDF15.

Main Results:

• GDF15 expression is governed by complex regulatory networks (e.g., ATF4/CHOP, AMPK, p53) and modulated by lifestyle interventions.
• GDF15 is implicated in obesity, diabetes, cardiovascular diseases, metabolic liver disorders, cachexia, sarcopenia, and aging.
• Various pharmacological agents and natural compounds can induce GDF15 expression.

Conclusions:

• GDF15 is a critical mediator in pan-metabolic health, with significant therapeutic potential for cardiometabolic diseases.
• Advances in GDF15-targeted drug development show promise, including monoclonal antibodies, fusion proteins, and small molecules.
• Further research is needed to address unresolved issues, including peripheral receptors and challenges in therapeutic development.