Prometheus’s Fire, Part III: The Forge of Hephaestus—Non-Pharmacological and Pharmacological Interventions Targeting Adipose Tissue Immunometabolism in Obesity
4 affiliations
- 1Lux Med Medical Centre in Warsaw, 49 Komitetu Obrony Robotników Street, 02-146 Warsaw, Poland
- 2Department of Endocrinology, Centre of Postgraduate Medical Education, Marymoncka Street 99/103, 01-813 Warsaw, Poland
- 3Centre of Postgraduate Medical Education, Marymoncka Street 99/103, 01-813 Warsaw, Poland
- 4Department of General Medicine and Geriatric Cardiology, Medical Centre of Postgraduate Education, ul. Czerniakowska 231, 00-416 Warsaw, Poland
Abstract
There is a growing recognition of obesity as a chronic immunometabolic disease in which impaired adipose tissue expandability contributes to a self-amplifying inflammatory network that extends across multiple organs. This state-of-the-art narrative review, the third and final part of the Prometheus’s Fire series, considers how lifestyle interventions, bariatric surgery and pharmacological therapies may disrupt this network and support the restoration of immunometabolic homeostasis. We introduce the concept of therapeutic convergence, describing how interventions with different primary mechanisms can influence shared processes, including NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activity, adipokine dysregulation, adipose tissue remodelling, mitochondrial stress and inter-organ inflammatory signalling. Evidence from randomised controlled trials, meta-analyses and mechanistic studies shows that these interventions differ considerably in the extent and breadth of their effects. Bariatric surgery, glucagon-like peptide-1 (GLP-1) receptor agonists and double GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (tirzepatide) have the most consistent evidence for coordinated effects on adipose tissue inflammation, metabolic dysfunction and inter-organ signalling. Other interventions appear to influence more selected components of the network and may therefore have greater value as complementary rather than comprehensive approaches. This perspective also highlights a limitation of relying on body weight as the primary measure of therapeutic success. Weight loss remains an important clinical goal, but it may not fully reflect the extent or durability of immunometabolic recovery. The therapeutic convergence framework therefore offers a way to understand how mechanistically distinct interventions can produce overlapping systemic benefits and may help identify treatment strategies that more effectively restore adipose tissue function while disrupting the inflammatory processes that sustain metabolic disease.
Related
- Targeting PAK1 Within Group I PAKs: Current Challenges and Pharmacological Perspectives.
- Pharmacological Interventions for Hereditary Transthyretin‐Related Amyloidosis With Polyneuropathy: Systematic Review and Network Meta‐Analysis
- PCSK9 in the Immunometabolism of Type 2 Diabetes
- RNA m6A Modification in Immunometabolism: Context-Dependent Mechanisms and Therapeutic Perspectives
- Short-chain fatty acids and intestinal macrophage immunometabolism in metabolic syndrome: mechanisms and implications for chronic low-grade inflammation
BibTeX
@article{grudniewska2026prometheuss,
title = {{Prometheus’s Fire, Part III: The Forge of Hephaestus—Non-Pharmacological and Pharmacological Interventions Targeting Adipose Tissue Immunometabolism in Obesity}},
author = {Anna Grudniewska and Beata Mrozikiewicz-Rakowska and Kacper Wiszniewski and Krzysztof J. Filipiak and Alina Kuryłowicz},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219692},
url = {https://www.mdpi.com/1422-0067/27/21/9692},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prometheus’s Fire, Part III: The Forge of Hephaestus—Non-Pharmacological and Pharmacological Interventions Targeting Adipose Tissue Immunometabolism in Obesity
AU - Anna Grudniewska
AU - Beata Mrozikiewicz-Rakowska
AU - Kacper Wiszniewski
AU - Krzysztof J. Filipiak
AU - Alina Kuryłowicz
PY - 2026
DA - 2026/10/29
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219692
UR - https://www.mdpi.com/1422-0067/27/21/9692
AB - There is a growing recognition of obesity as a chronic immunometabolic disease in which impaired adipose tissue expandability contributes to a self-amplifying inflammatory network that extends across multiple organs. This state-of-the-art narrative review, the third and final part of the Prometheus’s Fire series, considers how lifestyle interventions, bariatric surgery and pharmacological therapies may disrupt this network and support the restoration of immunometabolic homeostasis. We introduce the concept of therapeutic convergence, describing how interventions with different primary mechanisms can influence shared processes, including NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activity, adipokine dysregulation, adipose tissue remodelling, mitochondrial stress and inter-organ inflammatory signalling. Evidence from randomised controlled trials, meta-analyses and mechanistic studies shows that these interventions differ considerably in the extent and breadth of their effects. Bariatric surgery, glucagon-like peptide-1 (GLP-1) receptor agonists and double GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (tirzepatide) have the most consistent evidence for coordinated effects on adipose tissue inflammation, metabolic dysfunction and inter-organ signalling. Other interventions appear to influence more selected components of the network and may therefore have greater value as complementary rather than comprehensive approaches. This perspective also highlights a limitation of relying on body weight as the primary measure of therapeutic success. Weight loss remains an important clinical goal, but it may not fully reflect the extent or durability of immunometabolic recovery. The therapeutic convergence framework therefore offers a way to understand how mechanistically distinct interventions can produce overlapping systemic benefits and may help identify treatment strategies that more effectively restore adipose tissue function while disrupting the inflammatory processes that sustain metabolic disease.
SN - 1422-0067
ER -