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Isolation of Rat Adipose Tissue Mesenchymal Stem Cells for Differentiation into Insulin-producing Cells
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Insulin resistance causes inflammation in adipose tissue
Mitsugu Shimobayashi1, Verena Albert1, Bettina Woelnerhanssen2
1Biozentrum, University of Basel, Basel, Switzerland.
The Journal of Clinical Investigation
|March 13, 2018
Summary
Obesity-induced insulin resistance in mice triggers adipose tissue inflammation by increasing monocyte chemoattractant protein 1 (MCP1), rather than inflammation causing insulin resistance.
Area of Science:
- Metabolic Diseases
- Immunology
- Adipose Tissue Biology
Background:
- Obesity is a significant risk factor for insulin resistance and type 2 diabetes.
- Obesity-associated insulin resistance in adipose tissue correlates with inflammation and proinflammatory macrophage accumulation, but the causal link is uncertain.
Purpose of the Study:
- To investigate the causal relationship between adipose tissue insulin resistance and inflammation in obesity.
- To determine whether insulin resistance precedes or follows macrophage accumulation and inflammation in adipose tissue.
Main Methods:
- Utilized a mouse model with genetically induced, adipose-specific insulin resistance (mTORC2-knockout) combined with diet-induced obesity.
- Analyzed adipose tissue for macrophage infiltration, inflammation markers, and chemokine production (MCP1).
- Correlated insulin resistance (HOMA-IR), mTORC2 signaling, and MCP1 levels in visceral adipose tissue from obese human subjects.
Main Results:
- Obesity-induced insulin resistance in mice precedes macrophage accumulation and adipose tissue inflammation.
- Adipocyte insulin resistance leads to increased production of monocyte chemoattractant protein 1 (MCP1), recruiting monocytes and activating proinflammatory macrophages.
- In obese humans, insulin resistance (high HOMA-IR) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 in visceral adipose tissue.
Conclusions:
- Insulin resistance in adipose tissue is a primary driver of local inflammation.
- Adipocyte-derived MCP1 plays a crucial role in mediating insulin resistance-induced inflammation.
- These findings suggest a paradigm shift where insulin resistance initiates adipose tissue inflammation.
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