Prometheus’s Fire, Part II: The Hydra of Inflammation—Multiorgan Self-Amplifying Inflammatory Loops in Obesity: Molecular Crosstalk Between Adipose Tissue, Liver, Skeletal Muscle, Pancreas and Cardiovascular System
- 1Lux Med Medical Centre in Warsaw, 49 Komitetu Obrony Robotników Street, 02-146 Warsaw, Poland
- 2Department of Endocrinology, Centre of Postgraduate Medical Education, Marymoncka St. 99/103, 01-813 Warsaw, Poland
- 3Department of General Medicine and Geriatric Cardiology, Medical Centre of Postgraduate Education, 00-401 Warsaw, Poland
Abstract
Obesity should no longer be regarded as a disease confined to adipose tissue. Contemporary evidence indicates that adipose tissue dysfunction can initiate a cascade of metabolic and inflammatory responses that progressively involve multiple peripheral organs. Drawing on current molecular and translational evidence, we delineate mechanisms through which lipotoxicity, oxidative and endoplasmic reticulum stress, NLRP3 inflammasome activation and adipokine dysregulation contribute to inflammatory and metabolic dysfunction in the liver, skeletal muscle, pancreatic β-cells, vascular endothelium, perivascular adipose tissue and tumour microenvironment. Once established, organ-specific processes may become partially self-reinforcing and reciprocally amplify systemic immunometabolic dysfunction. We propose the Hydra of Inflammation as an integrative framework in which peripheral organs function not only as targets of adipose tissue-derived signals but also as secondary contributors to a progressively interconnected inflammatory network. This network-based perspective may help explain the heterogeneity of obesity-associated metabolic phenotypes and supports a shift from isolated organ-centred models towards systems-level approaches. The framework integrates the adipose tissue mechanisms discussed in Part I with the therapeutic perspectives developed in Part III of the Prometheus’s Fire series.
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BibTeX
@article{grudniewska2026prometheuss,
title = {{Prometheus’s Fire, Part II: The Hydra of Inflammation—Multiorgan Self-Amplifying Inflammatory Loops in Obesity: Molecular Crosstalk Between Adipose Tissue, Liver, Skeletal Muscle, Pancreas and Cardiovascular System}},
author = {Anna Grudniewska and Beata Mrozikiewicz-Rakowska and Kacper Wiszniewski and Piotr Dudek and Alina Kuryłowicz},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209356},
url = {https://www.mdpi.com/1422-0067/27/20/9356},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prometheus’s Fire, Part II: The Hydra of Inflammation—Multiorgan Self-Amplifying Inflammatory Loops in Obesity: Molecular Crosstalk Between Adipose Tissue, Liver, Skeletal Muscle, Pancreas and Cardiovascular System
AU - Anna Grudniewska
AU - Beata Mrozikiewicz-Rakowska
AU - Kacper Wiszniewski
AU - Piotr Dudek
AU - Alina Kuryłowicz
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209356
UR - https://www.mdpi.com/1422-0067/27/20/9356
AB - Obesity should no longer be regarded as a disease confined to adipose tissue. Contemporary evidence indicates that adipose tissue dysfunction can initiate a cascade of metabolic and inflammatory responses that progressively involve multiple peripheral organs. Drawing on current molecular and translational evidence, we delineate mechanisms through which lipotoxicity, oxidative and endoplasmic reticulum stress, NLRP3 inflammasome activation and adipokine dysregulation contribute to inflammatory and metabolic dysfunction in the liver, skeletal muscle, pancreatic β-cells, vascular endothelium, perivascular adipose tissue and tumour microenvironment. Once established, organ-specific processes may become partially self-reinforcing and reciprocally amplify systemic immunometabolic dysfunction. We propose the Hydra of Inflammation as an integrative framework in which peripheral organs function not only as targets of adipose tissue-derived signals but also as secondary contributors to a progressively interconnected inflammatory network. This network-based perspective may help explain the heterogeneity of obesity-associated metabolic phenotypes and supports a shift from isolated organ-centred models towards systems-level approaches. The framework integrates the adipose tissue mechanisms discussed in Part I with the therapeutic perspectives developed in Part III of the Prometheus’s Fire series.
SN - 1422-0067
ER -