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Insulin resistance causes inflammation in adipose tissue
- Publication Year :
- 2018
- Publisher :
- American Society for Clinical Investigation, 2018.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Chemokine
Panniculitis
medicine.medical_treatment
Adipose tissue
Inflammation
Mechanistic Target of Rapamycin Complex 2
Type 2 diabetes
Intra-Abdominal Fat
Proinflammatory cytokine
Mice
03 medical and health sciences
0302 clinical medicine
Insulin resistance
3T3-L1 Cells
Internal medicine
Animals
Humans
Medicine
Obesity
Chemokine CCL2
Mice, Knockout
biology
business.industry
Macrophages
Insulin
General Medicine
medicine.disease
030104 developmental biology
Endocrinology
Diabetes Mellitus, Type 2
030220 oncology & carcinogenesis
biology.protein
Homeostatic model assessment
Insulin Resistance
medicine.symptom
business
Research Article
Signal Transduction
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....838de22c3c5cb27d278387f07a5e9466
- Full Text :
- https://doi.org/10.5451/unibas-ep62220