Fatty acid dysregulation in asthma: linking immunometabolic remodeling, phenotypic heterogeneity, and metabolic precision medicine
- 1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Naval Medical University
- 2Sichuan University
Abstract
Asthma is a highly heterogeneous chronic airway disease characterized by diverse inflammatory endotypes, variable airway remodeling patterns, and differential therapeutic responses. Although current classifications mainly rely on immune phenotypes, they do not fully explain severe steroid resistance, obesity-associated asthma, and inflammation-independent structural remodeling. Immunometabolic dysregulation, particularly fatty acid metabolic imbalance, has emerged as an additional dimension associated with asthma heterogeneity and the interplay among systemic metabolic status with airway inflammation and remodeling. In this review, we summarize major features of fatty acid dysregulation in asthma, including altered circulating and airway lipid profiles, PUFA-derived mediator imbalance, SFA-associated metabolic stress, and cell-type-specific alterations in fatty acid uptake, synthesis, oxidation, and storage. These alterations may affect airway epithelial cells, macrophages, lymphocytes, airway smooth muscle cells, and fibroblasts, thereby influencing epithelial barrier integrity, inflammatory programming, smooth muscle remodeling, and extracellular matrix deposition. Human studies have identified phenotype-associated lipid signatures, including AA-derived inflammatory mediators such as cysteinyl leukotrienes and PGD2 metabolites in T2-high asthma and alterations in linoleic acid and glycerophospholipid metabolism across granulocytic phenotypes, whereas obesity-associated asthma additionally reflects systemic metabolic disturbances arising from the adipose–lung axis. Much of the current human evidence remains associative, whereas functional support for specific fatty acids, lipid mediators, and metabolic pathways is derived largely from experimental and ex vivo studies. We further present a conceptual framework in which metabolic, inflammatory, and structural alterations may interact to contribute to persistent airway remodeling. Finally, we discuss the emerging translational potential of lipidomic-guided phenotyping and metabolism-directed interventions, while emphasizing that these approaches remain investigational and require prospective clinical validation.
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BibTeX
@article{yuan2026fatty,
title = {{Fatty acid dysregulation in asthma: linking immunometabolic remodeling, phenotypic heterogeneity, and metabolic precision medicine}},
author = {Yuan Yuan and Yunhao Peng},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1974223},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1974223/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Fatty acid dysregulation in asthma: linking immunometabolic remodeling, phenotypic heterogeneity, and metabolic precision medicine
AU - Yuan Yuan
AU - Yunhao Peng
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1974223
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1974223/full
AB - Asthma is a highly heterogeneous chronic airway disease characterized by diverse inflammatory endotypes, variable airway remodeling patterns, and differential therapeutic responses. Although current classifications mainly rely on immune phenotypes, they do not fully explain severe steroid resistance, obesity-associated asthma, and inflammation-independent structural remodeling. Immunometabolic dysregulation, particularly fatty acid metabolic imbalance, has emerged as an additional dimension associated with asthma heterogeneity and the interplay among systemic metabolic status with airway inflammation and remodeling. In this review, we summarize major features of fatty acid dysregulation in asthma, including altered circulating and airway lipid profiles, PUFA-derived mediator imbalance, SFA-associated metabolic stress, and cell-type-specific alterations in fatty acid uptake, synthesis, oxidation, and storage. These alterations may affect airway epithelial cells, macrophages, lymphocytes, airway smooth muscle cells, and fibroblasts, thereby influencing epithelial barrier integrity, inflammatory programming, smooth muscle remodeling, and extracellular matrix deposition. Human studies have identified phenotype-associated lipid signatures, including AA-derived inflammatory mediators such as cysteinyl leukotrienes and PGD2 metabolites in T2-high asthma and alterations in linoleic acid and glycerophospholipid metabolism across granulocytic phenotypes, whereas obesity-associated asthma additionally reflects systemic metabolic disturbances arising from the adipose–lung axis. Much of the current human evidence remains associative, whereas functional support for specific fatty acids, lipid mediators, and metabolic pathways is derived largely from experimental and ex vivo studies. We further present a conceptual framework in which metabolic, inflammatory, and structural alterations may interact to contribute to persistent airway remodeling. Finally, we discuss the emerging translational potential of lipidomic-guided phenotyping and metabolism-directed interventions, while emphasizing that these approaches remain investigational and require prospective clinical validation.
SN - 1664-3224
ER -