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Cited by 1,180Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes

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Zatterale, Federica, Longo, Michele, Naderi, Jamal, Raciti, Gregory Alexander, Desiderio, Antonella, Miele, Claudia, Beguinot, Francesco·2020·Frontiers in Physiology
DOI 10.3389/fphys.2019.01607PMC PMC7000657
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Abstract

Obesity is one of the major health burdens of the 21st century as it contributes to the growing prevalence of its related comorbidities, including insulin resistance and type 2 diabetes. Growing evidence suggests a critical role for overnutrition in the development of low-grade inflammation. Specifically, chronic inflammation in adipose tissue is considered a crucial risk factor for the development of insulin resistance and type 2 diabetes in obese individuals. The triggers for adipose tissue inflammation are still poorly defined. However, obesity-induced adipose tissue expansion provides a plethora of intrinsic signals (e.g., adipocyte death, hypoxia, and mechanical stress) capable of initiating the inflammatory response. Immune dysregulation in adipose tissue of obese subjects results in a chronic low-grade inflammation characterized by increased infiltration and activation of innate and adaptive immune cells. Macrophages are the most abundant innate immune cells infiltrating and accumulating into adipose tissue of obese individuals; they constitute up to 40% of all adipose tissue cells in obesity. In obesity, adipose tissue macrophages are polarized into pro-inflammatory M1 macrophages and secrete many pro-inflammatory cytokines capable of impairing insulin signaling, therefore promoting the progression of insulin resistance. Besides macrophages, many other immune cells (e.g., dendritic cells, mast cells, neutrophils, B cells, and T cells) reside in adipose tissue during obesity, playing a key role in the development of adipose tissue inflammation and insulin resistance. The association of obesity, adipose tissue inflammation, and metabolic diseases makes inflammatory pathways an appealing target for the treatment of obesity-related metabolic complications. In this review, we summarize the molecular mechanisms responsible for the obesity-induced adipose tissue inflammation and progression toward obesity-associated comorbidities and highlight the current therapeutic strategies.

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Authors
Zatterale, F., Longo, M., Naderi, J., Raciti, G. A., Desiderio, A., Miele, C., & Beguinot, F.
Affiliations
  • Institute for Experimental Endocrinology and Oncology (IT)
  • University of Campania "Luigi Vanvitelli" (IT)
ORCID
Venue
Frontiers in Physiology
Publisher
Frontiers Media SA
Published
2020-01-29
Volume
10
Pages
1607-1607
ISSN
1664-042X (ISSN-L)
DOI
10.3389/fphys.2019.01607
PMC
PMC7000657
OpenAlex
W3003265560
Cited by
1,180
References
49
Citations by year
2026: 196 · 2025: 245 · 2024: 185 · 2023: 189 · 2022: 176 · 2021: 137 · 2020: 49 · 2018: 1
FWCI
20.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Physiology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • European Commission (2014‐2020, 665403, PRIN 2017, HORIZON2020, POR FESR 2014-2020)
  • Regione Campania (POR FESR 2014/2020, FESR 2014 2020)
  • European Regional Development Fund (FESR 2014-2020, 2014-2020’, POR FESR 2014-2020)
  • H2020 Marie Skłodowska-Curie Actions (665403, HORIZON2020)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords
adipose tissue inflammation, obesity, insulin resistance, type 2 diabetes, low-grade inflammation, adipose tissue macrophages, M1 macrophage polarization, inflammatory cytokines, immune cell infiltration, adipocyte death, hypoxia, mechanical stress, dendritic cells, mast cells, neutrophils, T cells, B cells, insulin signaling

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