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Regulation of Obesity-Related Insulin Resistance with Gut Anti-inflammatory Agents
- Source :
- Cell Metabolism. 21:527-542
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- SummaryObesity has reached epidemic proportions, but little is known about its influence on the intestinal immune system. Here we show that the gut immune system is altered during high-fat diet (HFD) feeding and is a functional regulator of obesity-related insulin resistance (IR) that can be exploited therapeutically. Obesity induces a chronic phenotypic pro-inflammatory shift in bowel lamina propria immune cell populations. Reduction of the gut immune system, using beta7 integrin-deficient mice (Beta7null), decreases HFD-induced IR. Treatment of wild-type HFD C57BL/6 mice with the local gut anti-inflammatory, 5-aminosalicylic acid (5-ASA), reverses bowel inflammation and improves metabolic parameters. These beneficial effects are dependent on adaptive and gut immunity and are associated with reduced gut permeability and endotoxemia, decreased visceral adipose tissue inflammation, and improved antigen-specific tolerance to luminal antigens. Thus, the mucosal immune system affects multiple pathways associated with systemic IR and represents a novel therapeutic target in this disease.
- Subjects :
- medicine.medical_specialty
Integrin beta Chains
Physiology
Blotting, Western
Anti-Inflammatory Agents
Adipose tissue
Inflammation
Biology
Diet, High-Fat
Mice
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Immune system
Antigen
Immunity
Internal medicine
medicine
Animals
Obesity
Mesalamine
Immunity, Mucosal
Molecular Biology
030304 developmental biology
0303 health sciences
Lamina propria
Mucous Membrane
Histological Techniques
digestive, oral, and skin physiology
Cell Biology
Flow Cytometry
medicine.disease
Immunohistochemistry
3. Good health
Gastrointestinal Tract
Mice, Inbred C57BL
Endocrinology
medicine.anatomical_structure
Mucosal immunology
030220 oncology & carcinogenesis
Immunology
Cytokines
Insulin Resistance
medicine.symptom
Subjects
Details
- ISSN :
- 15504131
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Cell Metabolism
- Accession number :
- edsair.doi.dedup.....e8225cd725ed0f9ca1aeb0ae816c3075