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Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity
- Source :
- Cell. 171:372-384.e12
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- MiRNAs are regulatory molecules that can be packaged into exosomes and secreted from cells. Here, we show that adipose tissue macrophages (ATMs) in obese mice secrete miRNA-containing exosomes (Exos), which cause glucose intolerance and insulin resistance when administered to lean mice. Conversely, ATM Exos obtained from lean mice improve glucose tolerance and insulin sensitivity when administered to obese recipients. miR-155 is one of the miRNAs overexpressed in obese ATM Exos, and earlier studies have shown that PPARĪ³ is a miR-155 target. Our results show that miR-155KO animals are insulin sensitive and glucose tolerant compared to controls. Furthermore, transplantation of WT bone marrow into miR-155KO mice mitigated this phenotype. Taken together, these studies show that ATMs secrete exosomes containing miRNA cargo. These miRNAs can be transferred to insulin target cell types through mechanisms of paracrine or endocrine regulation with robust effects on cellular insulin action, in vivo insulin sensitivity, and overall glucose homeostasis.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
medicine.medical_treatment
Adipose tissue macrophages
Adipose tissue
Biology
Carbohydrate metabolism
General Biochemistry, Genetics and Molecular Biology
Mice
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Internal medicine
Adipocytes
medicine
Animals
Glucose homeostasis
Muscle, Skeletal
Cells, Cultured
Muscle Cells
Macrophages
Insulin
medicine.disease
Microvesicles
Mice, Inbred C57BL
Transplantation
MicroRNAs
Glucose
030104 developmental biology
Endocrinology
Adipose Tissue
Liver
030220 oncology & carcinogenesis
Hepatocytes
Insulin Resistance
Signal Transduction
Subjects
Details
- ISSN :
- 00928674
- Volume :
- 171
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....b3a1044d3743a912cd0e6c218e2ab0d4