Cited by 4,143Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismImmune cells in cancer

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Inflammation, stress, and diabetes

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Wellen, Kathryn E., Hotamisligil, Gökhan S.·2005·Journal of Clinical Investigation

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Abstract

Over the last decade, an abundance of evidence has emerged demonstrating a close link between metabolism and immunity.It is now clear that obesity is associated with a state of chronic low-level inflammation.In this article, we discuss the molecular and cellular underpinnings of obesity-induced inflammation and the signaling pathways at the intersection of metabolism and inflammation that contribute to diabetes.We also consider mechanisms through which the inflammatory response may be initiated and discuss the reasons for the inflammatory response in obesity.We put forth for consideration some hypotheses regarding important unanswered questions in the field and suggest a model for the integration of inflammatory and metabolic pathways in metabolic disease. Inflammation, stress, and diabetesSurvival of multicellular organisms depends on the ability to fight infection and heal damage and the ability to store energy for times of low nutrient availability or high energy need.Metabolic and immune systems are therefore among the most basic requirements across the animal kingdom, and many nutrient and pathogen-sensing systems have been highly conserved from organisms such as Caenorhabditis elegans and Drosophila to mammals.Perhaps not surprisingly, metabolic and immune pathways have also evolved to be closely linked and interdependent.Many hormones, cytokines, signaling proteins, transcription factors, and bioactive lipids can function in both metabolic and immune roles.In addition to using some of the same cellular machinery, metabolic and immune systems also regulate each other.The normal inflammatory response relies upon metabolic support, and energy redistribution, particularly the mobilization of stored lipid, plays an important role in fighting infection during the acute-phase response (1).The basic inflammatory response thus favors a catabolic state and suppresses anabolic pathways, such as the highly conserved and powerful insulin signaling pathway.The integration of metabolism and immunity, which under normal conditions is beneficial for the maintenance of good health, can become deleterious under conditions of metabolic challenge, as exemplified by the immunosuppression characteristic of malnourished or starving individuals (1-3).Famine has been a prominent hazard to human health throughout history, and for thousands of years the link between infection and poor nutrition has been well recognized.Today this threat is as widespread as ever, and there are approximately 1 billion undernourished individuals worldwide (3).In the past century, however, the pendulum has also swung in the opposite direction, and now as many if not more people are overweight or obese (4).With the advent of this chronic metabolic overload, a new set of problems and complications at the intersection of metabolism and immunity has emerged, including the obesity-linked inflammatory diseases diabetes, fatty liver disease, airway inflammation, and atherosclerosis (5).There is now a wealth of evidence indicating close ties between metabolic and immune systems.Among the many reasons to

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1 retracted

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Authors: Wellen, K. E., & Hotamisligil, G. S.
Affiliations: Harvard University (US)
ORCID: Wellen, Kathryn E.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2005-05-02
Volume: 115
Issue: 5
Pages: 1111-1119
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci25102
PMC: PMC1087185
OpenAlex: W2064119981
Cited by: 4,143
References: 118
Citations by year: 2026: 76 · 2025: 104 · 2024: 92 · 2023: 130 · 2022: 177 · 2021: 169 · 2020: 209 · 2019: 221 · 2018: 233 · 2017: 193 · 2016: 215 · 2015: 226 · 2014: 239 · 2013: 276 · 2012: 264
FWCI: 138.15
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Diabetes Association
National Institutes of Health
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: obesity-associated inflammation, low-grade inflammation, type 2 diabetes, insulin signaling, stress response, innate immunity, innate lymphoid cells, Th17 cells, Th1 cells, Th2 cells, regulatory T cells, Treg cell function, Treg cell homeostasis
MeSH terms: Animals, Diabetes Mellitus, Humans, Inflammation, Insulin Resistance, Macrophages, Obesity, Stress, Physiological, Adipocytes

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