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Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Macrophages, inflammation, and insulin resistance
Jerrold M Olefsky1, Christopher K Glass
1Department of Medicine, University of California-San Diego, La Jolla, CA 92093-0651, USA. jolefsky@ucsd.edu
Annual Review of Physiology
|February 13, 2010
Summary
Obesity causes insulin resistance and type 2 diabetes by promoting inflammatory M1 macrophages. Targeting this inflammation while preserving immunity may offer new therapies for metabolic dysfunction.
Area of Science:
- Metabolic disease
- Immunology
- Molecular biology
Background:
- Obesity is a major risk factor for type 2 diabetes mellitus.
- Obesity-induced insulin resistance involves impaired insulin target cells and macrophage accumulation.
- Macrophages secrete proinflammatory mediators, contributing to insulin resistance.
Purpose of the Study:
- To elucidate the molecular mechanisms linking obesity, inflammation, and insulin resistance.
- To identify key molecular players in macrophage polarization during obesity.
- To explore potential therapeutic strategies targeting the inflammation-insulin resistance axis.
Main Methods:
- Analysis of molecular signaling pathways in insulin-resistant tissues (adipose, liver, muscle).
- Investigation of macrophage polarization states (M1 vs. M2) and their regulatory factors.
- Examination of transcription factors involved in innate immunity and inflammation.
Main Results:
- Obesity promotes a shift in macrophage polarization from M2 to M1 states.
- STAT6 and PPARs are associated with M2 macrophages, while NF-kappaB and AP1 drive M1 polarization.
- This M1 polarization is linked to the development of insulin resistance.
Conclusions:
- The transition of macrophages to an M1 inflammatory state is a key molecular event in obesity-induced insulin resistance.
- Targeting the inflammation/insulin resistance axis, while preserving innate immunity, presents a promising therapeutic avenue.
- Understanding these molecular pathways could lead to novel treatments for type 2 diabetes.
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