Emerging Roles of GDF15 in Metabolic and Cardiovascular Diseases.
Level 5 - mechanism / opinion, no new human data
Narrative review without original human data or systematic review methodology
PubMed 40837873 · doi:10.34133/research.0832
What was done
This narrative review synthesizes literature on the expression, regulation, physiological roles, and therapeutic targeting of Growth Differentiation Factor 15 (GDF15). The authors describe its molecular regulatory networks (such as ATF4/CHOP, AMPK, EGR1, EZH2, PPARgamma, NRF2, ERRgamma, p53, and CNOT6L), signaling mediated by the GFRAL receptor, interactions with metabolic factors like FGF21 and GLP-1, regulation by diet and exercise, and pharmacologic strategies including monoclonal antibodies, fusion proteins, and small molecules.
What was found
The abstract reports no numerical data or effect sizes. It qualitatively describes GDF15 as a stress-responsive cytokine that regulates appetite, metabolism, and inflammation through GFRAL-mediated pathways, with implicated roles across obesity, diabetes, cardiovascular diseases, metabolic liver disorders, cachexia, sarcopenia, and aging. It also notes unresolved contradictions in cardiometabolic literature and ongoing challenges in drug development.
Why it matters
The paper synthesizes the biological mechanisms and translational pipeline for GDF15, framing its dual relevance as a metabolic regulator and therapeutic target.
Limits
This is a non-systematic narrative review providing no primary human or animal data. The abstract acknowledges unresolved questions in the field, including contradictory findings regarding cardiometabolic effects and an incomplete understanding of potential peripheral receptors. No search protocol, study count, or quantitative outcomes are reported.
Cited by
- context A clinical trial evaluating a GDF15-blocking antibody in heart failure was terminated because participants receiving the drug developed more heart failure and adverse events.