Insulin resistance causes inflammation in adipose tissue
Open accessAbstract
Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activates proinflammatory macrophages. Finally, insulin resistance (high homeostatic model assessment of insulin resistance [HOMA-IR]) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in visceral adipose tissue from obese human subjects. Our findings suggest that insulin resistance in adipose tissue leads to inflammation rather than vice versa.
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In adipocytes, IR by impaired insulin/mTOR2 signaling results in increased MCP1 production, which results in increased circulating MCP1.
“In adipocytes, IR by impaired insulin/mTOR2 signaling results in increased MCP1 production, which results in increased circulating MCP1.”
From Sarcopenic obesity, insulin resistance, and their implications in cardiovascular and metabolic consequences (2020) · cites this paper as [109]
Myocardial fibrosis is closely associated with sarcopenic obesity.
“Myocardial fibrosis, another well-established cardiac ailment and pathological hazard for a multitude of CVDs, is closely associated with sarcopenic obesity.”
From Sarcopenic obesity: epidemiology, pathophysiology, cardiovascular disease, mortality, and management (2023) · cites this paper as [55]
Overexpressed TNF-α and chronic oxidative stress stimulate myofibroblasts and activate profibrotic signaling pathways, respectively, thereby promoting collagen production and inducing cardiac fibrosis.
“This is substantiated by robust evidence indicating the roles of overexpressed TNF-α and chronic oxidative stress. These factors stimulate myofibroblasts and activate profibrotic signaling pathways, respectively, thereby promoting collagen production and inducing cardiac fibrosis (55).”
From Sarcopenic obesity: epidemiology, pathophysiology, cardiovascular disease, mortality, and management (2023) · cites this paper as [55]
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References 75 · Cited by 480
- Authors
- Shimobayashi, M., Albert, V., Woelnerhanssen, B., Frei, I. C., Weissenberger, D., Meyer-Gerspach, A. C., Clement, N., Moes, S., Colombi, M., Meier, J. A., Swierczynska, M. M., Jenö, P., Beglinger, C., Peterli, R., & Hall, M. N.
- Affiliations
- University of Basel (CH)
- St. Claraspital (CH)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2018-03-12
- Volume
- 128
- Issue
- 4
- Pages
- 1538-1550
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5873875
- OpenAlex
- W2792246690
- Cited by
- 480
- References
- 75
- Citations by year
- 2026: 45 · 2025: 56 · 2024: 67 · 2023: 64 · 2022: 64 · 2021: 71 · 2020: 59 · 2019: 33 · 2018: 20 · 2017: 1
- FWCI
- 35.69
- 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)
- edoc (University of Basel) (acceptedVersion)
- Lirias (KU Leuven) (submittedVersion)
- edoc (University of Basel)
- Funders
- National Science Foundation
- École Polytechnique Fédérale de Lausanne
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- 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
- insulin resistance, adipose tissue inflammation, obesity, macrophage accumulation, mTORC2, MCP-1, monocyte recruitment, adipocytes, type 2 diabetes, visceral adipose tissue, HOMA-IR
- MeSH terms
- Mechanistic Target of Rapamycin Complex 2, Animals, Diabetes Mellitus, Type 2, Humans, Inflammation, Insulin Resistance, Macrophages, Obesity, Signal Transduction, Panniculitis, Mice, Knockout, Chemokine CCL2, 3T3-L1 Cells, Intra-Abdominal Fat, Mice
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