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Peer-reviewedCC BYCells

GDF-15/GFRAL Axis Dynamics and Vulnerability Windows in Bariatric Surgery: Pathophysiological, Microbiomic, and Pharmacological Perspectives

  • Alin Constantin Pînzariu1,2
  • Ionela Lăcrămioara Șerban1
  • Radu Petru Soroceanu1,2
  • Vlad Ionuț Vlăsceanu1,2
  • Madalina Maxim1,2
  • Ancuta Andreea Miler1
  • Sebastian Marian Leonte1
  • Carmen Atodiresei1,3
  • Mihaela Moscalu1
  • Lorena Mihaela Manole1,4
  • Laura Mihaela Trandafir1,4
  • Dragomir Nicolae Șerban1
1 more authors
  • Daniel Vasile Timofte1
4 affiliations
  1. 1Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
  2. 2Department of Surgery, Sf. Spiridon County Emergency Clinical Hospital, 700111 Iasi, Romania
  3. 3Institute of Gastroenterology and Hepatology, Sf. Spiridon County Emergency Clinical Hospital, 700111 Iasi, Romania
  4. 4Sfânta Maria Emergency Children Hospital, 700309 Iași, Romania
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Abstract

Bariatric surgery (BS) and new pharmacological treatments cause significant neurometabolic changes. However, the pathways linking peripheral stress to central metabolic control remain poorly understood. This review highlights the GDF-15/GFRAL/RET complex as a key integrator of multiorgan-to-brain stress signals that shape systemic metabolic adaptation after surgical and pharmacological interventions. Based on a structured search across PubMed, Embase, Scopus, Google Scholar, and Web of Science covering 2020–2026 alongside foundational studies, we integrated translational evidence from peer-reviewed human trials and mechanistic animal models to map the GDF-15/GFRAL/RET axis across bariatric and incretin domains. We examined the neurobiology of the GDF-15/GFRAL axis to clarify variability in metabolic and behavioral outcomes after BS. This axis links metabolic stress signals from the gut, liver, and adipose tissue to the hindbrain and hypothalamic regulation of energy balance. Changes in the gut microbiome and SCFA–FFAR2/FFAR3 signaling after surgery interact with GDF-15 and incretin pathways. Future studies should critically compare BS with synergistic or alternative non-invasive neurometabolic approaches such as incretin mimetics, exogenous GDF-15 therapies, and high-protein diets.

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Cite

BibTeXRIS
BibTeX
@article{pinzariu2026gdf15gfral,
  title = {{GDF-15/GFRAL Axis Dynamics and Vulnerability Windows in Bariatric Surgery: Pathophysiological, Microbiomic, and Pharmacological Perspectives}},
  author = {Alin Constantin Pînzariu and Ionela Lăcrămioara Șerban and Radu Petru Soroceanu and Vlad Ionuț Vlăsceanu and Madalina Maxim and Ancuta Andreea Miler and Sebastian Marian Leonte and Carmen Atodiresei and Mihaela Moscalu and Lorena Mihaela Manole and Laura Mihaela Trandafir and Dragomir Nicolae Șerban and Daniel Vasile Timofte},
  journal = {Cells},
  year = {2026},
  month = oct,
  doi = {10.3390/cells15191823},
  url = {https://europepmc.org/article/PMC/PMC13664289},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - GDF-15/GFRAL Axis Dynamics and Vulnerability Windows in Bariatric Surgery: Pathophysiological, Microbiomic, and Pharmacological Perspectives
AU  - Alin Constantin Pînzariu
AU  - Ionela Lăcrămioara Șerban
AU  - Radu Petru Soroceanu
AU  - Vlad Ionuț Vlăsceanu
AU  - Madalina Maxim
AU  - Ancuta Andreea Miler
AU  - Sebastian Marian Leonte
AU  - Carmen Atodiresei
AU  - Mihaela Moscalu
AU  - Lorena Mihaela Manole
AU  - Laura Mihaela Trandafir
AU  - Dragomir Nicolae Șerban
AU  - Daniel Vasile Timofte
PY  - 2026
DA  - 2026/10/01
JO  - Cells
DO  - 10.3390/cells15191823
UR  - https://europepmc.org/article/PMC/PMC13664289
AB  - Bariatric surgery (BS) and new pharmacological treatments cause significant neurometabolic changes. However, the pathways linking peripheral stress to central metabolic control remain poorly understood. This review highlights the GDF-15/GFRAL/RET complex as a key integrator of multiorgan-to-brain stress signals that shape systemic metabolic adaptation after surgical and pharmacological interventions. Based on a structured search across PubMed, Embase, Scopus, Google Scholar, and Web of Science covering 2020–2026 alongside foundational studies, we integrated translational evidence from peer-reviewed human trials and mechanistic animal models to map the GDF-15/GFRAL/RET axis across bariatric and incretin domains. We examined the neurobiology of the GDF-15/GFRAL axis to clarify variability in metabolic and behavioral outcomes after BS. This axis links metabolic stress signals from the gut, liver, and adipose tissue to the hindbrain and hypothalamic regulation of energy balance. Changes in the gut microbiome and SCFA–FFAR2/FFAR3 signaling after surgery interact with GDF-15 and incretin pathways. Future studies should critically compare BS with synergistic or alternative non-invasive neurometabolic approaches such as incretin mimetics, exogenous GDF-15 therapies, and high-protein diets.
SN  - 2073-4409
ER  -