Adiposity / Obesity & Inflammation / Inflammatory Diseases

Overview

Adiposity / Obesity is a key environmental factor linked to the severity of various inflammatory disorders. Dysregulated lipid metabolism, especially elevated cholesterol levels, is associated with inflammation, including:

• Atherosclerosis


• Diabetes


• Dementia


• Psoriasis


• Gut dysbiosis (1)

Inflammation in Obesity

Obesity is primarily linked to chronic inflammation in adipose tissue (AT). Immune cell populations in adipose tissue change during weight fluctuations, contributing to:
* Insulin resistance

• Dysregulated adipocyte lipolysis (2)

Inflammation related to adiposity / obesity, aging, cancer, and sleep deprivation occurs without infection or tissue injury (3, 4, 5).

Obesity leads to ongoing, mild inflammation known as metainflammation. Characterized by elevated levels of inflammatory substances:

• Interleukin-6 (IL-6)


• Tumor Necrosis Factor alfa (TNF-alfa)


• Interleukin-1 (IL-1) beta (IL-1F2)
  Involves increased inflammatory cells like Ly6C hi monocytes, macrophages, and neutrophils (6, 7).

Obesity increases inflammation in the stomach and intestines, marked by pro-inflammatory intestinal macrophages and other immune cells like:
* Group 1 ILCs (ILC1)
* CD4+ Th1 Cells (11, 12, 13)
In adipose tissue, macrophages secrete pro-inflammatory cytokines inhibiting insulin signaling (14).

Immune Cells in Adipose Tissue

Adipose tissue contains various immune cells. Both innate and adaptive immune system cells coexist (8, 9, 10).
Macrophages

• T cells (CD4+, CD8+, regulatory T cells)


• B ells / B Lymphocytes


• Natural killer T cells


• Dendritic cells


• Neutrophils


• Eosinophils


• Mast cells

Immune Cells in Adipose Tissue - Neutrophils

Recent studies show significant alterations in neutrophils in obesity, with increased reactive oxygen species (ROS) release (15, 16, 17). In both humans and mice, obesity-induced neutrophil oxidative stress affects vascular function and migration (6, 18). In murine models, neutrophils infiltrate adipose tissue (AT) early during high-fat diet (HFD) feeding, promoting Interleukin-1 (IL-1) beta (IL-1F2) production and suggesting a crucial role in initiating diet-induced inflammation. (16, 19, 20). Neutrophil elastase contributes to myeloid cell production (20), and its genetic knockout in mice reduces obesity-induced metabolic dysfunction and inflammation (19). Despite these findings, the mechanisms driving proinflammatory shifts in obesity remain unclear, though altered cellular metabolism may play a role in leukocyte activation (21).

References

(1) Frascoli et al. 2022 J Immunol 209(4): 645-653
(2) Caslin et al. 2020 Immunol Rev 295: 101
(3) Medzhitov 2008 Nature 454: 428-435
(4) Franceschi et al. 2018a Nat. Rev. Endocrinol. 14: 576-590
(5) Besedovsky et al. 2019 Physiol. Rev. 99: 1325-1380
(6) Nagareddy et al. 2014 Cell Metab 19: 821-835
(7) Boroumand & Klip 2020 J Cell Sci 133: jcs238394
(8) Kanneganti & Dixit 2012 Nat Immunol. 13(8): 707-712
(9) Ivanov et al. 2018 Atherosclerosis 271: 102-110
(10) Dalmas 2019 Semin Immunopathol. 41(4): 531-545
(11) Monteiro-Sepulveda et al. 2015 Cell Metab 22: 113-124
(12) Yudanin et al. 2019 Immunity 50: 505
(13) Rohm et al. 2021 Front Immunol 12: 668654
(14) Wali et al. 2020 Nutrients 12: E1505
(15) Brotfain et al. 2015 Clin Exp Immunol 181: 156-163
(16) Elgazar-Carmon et al. 2008 J Lipid Res 49: 1894-1903
(17) Mancuso et al. 2022 Am J Physiol Lung Cell Mol Physiol 322: L116–L128
(18) McDowell et al. 2021 Nat Cancer 2: 545-562
(19) Talukdar et al. 2012 Nat Med 18: 1407-1412
(20) Huang et al. 2017 J Biol Chem 292: 4770-4776
(21) Bowers et al. 2025 The Journal of Immunology 214(4): 680-693

see also:
Cardiometabolic disease (CMD) & Risk Factors
Defending the Attack of Pathogens by Neutrophils
Inflammation / Inflammatory Diseases & Neutrophils / Neutrophilic Granulocytes
Insulin resistance & Neutrophils / Neutrophilic Granulocytes