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Inflammatory mechanisms linking obesity and metabolic disease
Open accessAbstract
There are currently over 1.9 billion people who are obese or overweight, leading to a rise in related health complications, including insulin resistance, type 2 diabetes, cardiovascular disease, liver disease, cancer, and neurodegeneration. The finding that obesity and metabolic disorder are accompanied by chronic low-grade inflammation has fundamentally changed our view of the underlying causes and progression of obesity and metabolic syndrome. We now know that an inflammatory program is activated early in adipose expansion and during chronic obesity, permanently skewing the immune system to a proinflammatory phenotype, and we are beginning to delineate the reciprocal influence of obesity and inflammation. Reviews in this series examine the activation of the innate and adaptive immune system in obesity; inflammation within diabetic islets, brain, liver, gut, and muscle; the role of inflammation in fibrosis and angiogenesis; the factors that contribute to the initiation of inflammation; and therapeutic approaches to modulate inflammation in the context of obesity and metabolic syndrome.
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“In obesity, adipose tissue is infiltrated by macrophages, resulting in the secretion of inflammatory adipokines and other factors that result in impaired glucose homeostasis (Gonzalez- Muniesa et al., 2017; Guh et al., 2009; Kusminski et al., 2016; Saltiel & Olefsky, 2017).”
BackgroundPoor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action
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The Impact of Exercise on Telomere Length, DNA Methylation and Metabolic Footprints
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“To mitigate these effects, the human innate immune system harbors cells that express LPS receptors, such as TLR4 and CD14, which elicit a strong inflammatory response to LPS[135].”
Multidrug-Resistant Infections and Metabolic Syndrome: An Overlooked Bidirectional Relationship
Acierno, C., Nevola, R., Barletta, F., Rinaldi, L., Sasso, F. C., Adinolfi, L. E., & Caturano, A. (2025) · Biomedicines · doi:10.3390/biomedicines13061343 · Cited by 20
“Low-grade chronic inflammation is a defining feature of metabolic syndrome (MetS) [35].”
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“Although the role of inflammation in human obesity is less clear, numerous studies have demonstrated a strong association between inflammatory signals, insulin resistance, and obesity (8, 9, 15–17).”
Self-citationCOVID-19 and Obesity: An Epidemiologic Analysis of the Brazilian Data
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“In this context, large amounts of cytokines and chemokines are released, and cells that produce proinflammatory molecules are recruited, culminating in unbalanced immune responses [18, 19].”
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“Furthermore, obese individuals had increased levels of endotoxin in the plasma (due to disturbances in intestinal barrier integrity) [68], leading to TLR4- and NF-κB-mediated inflammatory cytokine production, including IL-1β, TNFα, and IL-6 [29,69].”
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“type of inflammation is further linked to the development of insulin resistance [20,21] and can lead to fibrosis or necrosis [22].”
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“Since obesity is a chronic low-grade inflammation condition [10], recent studies have suggested a strong correlation between obesity and the development of progressive agingrelated neurodegenerative diseases [11].”
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“will be mostly turned into lipid intermediates and deposited in healthy non-adipose tissues, causing lipotoxicity and further tissue damage [12,13].”
BackgroundCoagulation factor dysregulation in polycystic ovary syndrome is an epiphenomenon of obesity
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Obesity, Preserved Ejection Fraction Heart Failure, and Left Ventricular Remodeling
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“On the one hand, obesity can cause chronic systematic inflammation, resulting in IR [57].”
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“In obesity, infiltrating inflammatory cells in adipose tissue chronically produces high levels of proinflammatory cytokines including interleukin-6 (IL-6), IL-17, and tumor necrosis factor-alpha (TNF-α) [38].”
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Key Role of Obesity in Genitourinary Tumors with Emphasis on Urothelial and Prostate Cancers
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“Along this line, macrophages in fat tissue appear enhanced in obese patients and exhibit a pro-inflammatory habit contributing to TNF-α production [82,83].”
BackgroundTrain to Lose: Innate Immune Memory in Metaflammation
Charles‐Messance, H., & Sheedy, F. J. (2020) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900480 · Cited by 18
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“Furthermore, the presence of low-grade chronic inflammatory condition in people with obesity is believed to facilitate MS [8].”
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“Previous studies also suggested that the increased number of inflammatory cells and their secretions such as cytokines induced an increased rate in differentiation and proliferation of adipocytes followed by fat accumulation, obesity, insulin resistance, and increased risks to cardiometabolic syndrome.(6) The T lympho…”
BackgroundCavalheiro, E. K. F. F., Costa, A. B., Salla, D. H., da Silva, M. R., Mendes, T. F., da Silva, L. E., Turatti, C. D. R., de Bitencourt, R. M., & Rezin, G. T. (2021) · Cannabis and Cannabinoid Research · doi:10.1089/can.2021.0016 · Cited by 22
Hypothalamic Overexpression of Neurosecretory Protein GL Leads to Obesity in Male C57BL/6J Mice
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Adipose Tissue in Health and Disease
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“Excessive weight gain leads to adipose tissue remodelling with the release of adipose-derived pro-inflammatory cytokines and free fatty acids into circulation, resulting in metabolic dys - function [ 52 ] and increased risk of chronic disease [ 53].”
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“Obesity is, indeed, one of the conditions predisposing to the metabolic syndrome and appears characterized by a chronic low-grade inflammation that can determine the onset of inter-related cardiovascular risk factors, which include visceral adiposity, insulin resistance, dyslipidemia, and hypertension.[3,26,27] It was…”
BackgroundPresence and significance of intestinal unicellular parasites in a morbidly obese population
Caudet-Esteban, J., Trelis, M., Cifre, S., Soriano, J. M., & Merino-Torres, J. F. (2021) · International Journal of Obesity · doi:10.1038/s41366-021-00980-6 · Cited by 19
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“Adipose tissue, especially white adipose tissues (WAT), mediates energy homeostasis in adults.((11,12)) The adipose tissue as an endocrine organ is capable to produce several hormones and a group of cytokines known as adipokines, such as adiponectin, resistin, and leptin, playing a central role in the regulation of me…”
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Metadata
- Authors
- Saltiel, A. R., & Olefsky, J. M.
- Affiliations
- University of California San Diego (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2017-01-03
- Volume
- 127
- Issue
- 1
- Pages
- 1-4
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5199709
- OpenAlex
- W2567264284
- Cited by
- 2,212
- References
- 44
- Citations by year
- 2026: 261 · 2025: 318 · 2024: 265 · 2023: 255 · 2022: 308 · 2021: 280 · 2020: 270 · 2019: 136 · 2018: 80 · 2017: 36
- FWCI
- 18.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- University of California, San Diego (P30DK063491, DK063491)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK063491, P30DK063491)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- obesity, metabolic syndrome, low-grade inflammation, insulin resistance, type 2 diabetes, adipose tissue expansion, innate immune system, adaptive immunity, neuroinflammation, liver inflammation, intestinal inflammation, skeletal muscle inflammation, fibrosis, angiogenesis, anti-inflammatory therapy
- MeSH terms
- Animals, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Humans, Inflammation, Neoplasms, Obesity, Organ Specificity, Neurodegenerative Diseases, Metabolic Syndrome
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