Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation
2019/01/21 by Yong Pan, Xiaoyan Hui, Ruby Lai Chong Hoo +7 · 31 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Extracellular vesicles in disease #Adipokines, Inflammation, and Metabolic Diseases #MicroRNA in disease regulation
paper · doi:10.1172/jci123069
Abstract
Persistent, unresolved inflammation in adipose tissue is a major contributor to obesity-associated metabolic complications. However, the molecular links between lipid-overloaded adipocytes and inflammatory immune cells in obese adipose tissues remain elusive. Here we identified adipocyte-secreted microRNA-34a (miR-34a) as a key mediator through its paracrine actions on adipose-resident macrophages. The expression of miR-34a in adipose tissues was progressively increased with the development of dietary obesity. Adipose-selective or adipocyte-specific miR-34a-KO mice were resistant to obesity-induced glucose intolerance, insulin resistance, and systemic inflammation, and this was accompanied by a significant shift in polarization of adipose-resident macrophages from proinflammatory M1 to antiinflammatory M2 phenotype. Mechanistically, mature adipocyte-secreted exosomes transported miR-34a into macrophages, thereby suppressing M2 polarization by repressing the expression of Krüppel-like factor 4 (Klf4). The suppressive effects of miR-34a on M2 polarization and its stimulation of inflammatory responses were reversed by ectopic expression of Klf4 in both bone marrow-derived macrophages and adipose depots of obese mice. Furthermore, increased miR-34a expression in visceral fat of overweight/obese subjects correlated negatively with reduced Klf4 expression, but positively with the parameters of insulin resistance and metabolic inflammation. In summary, miR-34a was a key component of adipocyte-secreted exosomal vesicles that transmitted the signal of nutrient overload to the adipose-resident macrophages for exacerbation of obesity-induced systemic inflammation and metabolic dysregulation.
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- The exosome-like vesicles from osteoarthritic chondrocyte enhanced mature IL-1β production of macrophages and aggravated synovitis in osteoarthritis. [europepmc]
- Interorgan communication by exosomes, adipose tissue, and adiponectin in metabolic syndrome. [europepmc]
- Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer. [europepmc]
- Macrophage miR-34a Is a Key Regulator of Cholesterol Efflux and Atherosclerosis. [europepmc]
- Macrophage metabolic reprogramming aggravates aortic dissection through the HIF1α-ADAM17 pathway ✰ . [europepmc]
- A review on the biology and properties of adipose tissue macrophages involved in adipose tissue physiological and pathophysiological processes. [europepmc]
- Immune checkpoint inhibitor induces cardiac injury through polarizing macrophages via modulating microRNA-34a/Kruppel-like factor 4 signaling. [europepmc]
- The crosstalk: exosomes and lipid metabolism. [europepmc]
- Epigenetic signatures underlying inflammation: an interplay of nutrition, physical activity, metabolic diseases, and environmental factors for personalized nutrition. [europepmc]
- Adipose Extracellular Vesicles in Intercellular and Inter-Organ Crosstalk in Metabolic Health and Diseases. [europepmc]
- Innate Immune Cells in the Adipose Tissue in Health and Metabolic Disease. [europepmc]
- Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses. [europepmc]
- Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes. [europepmc]
- Exosomes as mediators of intercellular crosstalk in metabolism. [europepmc]
- Extracellular vesicles: mediators of intercellular communication in tissue injury and disease. [europepmc]
- Roles and mechanisms of exosomal non-coding RNAs in human health and diseases. [europepmc]
- Macrophage Polarization and Its Role in Liver Disease. [europepmc]
- Angiogenesis in adipose tissue and obesity. [europepmc]
- Extracellular Matrix (ECM) and Fibrosis in Adipose Tissue: Overview and Perspectives. [europepmc]
- Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo. [europepmc]
- Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study. [europepmc]
- Overview and New Insights into the Metabolic Syndrome: Risk Factors and Emerging Variables in the Development of Type 2 Diabetes and Cerebrocardiovascular Disease. [europepmc]
- An update on the secretory functions of brown, white, and beige adipose tissue: Towards therapeutic applications. [europepmc]
- Emerging mechanisms of obesity-associated immune dysfunction. [europepmc]
- Macrophage polarization: an important role in inflammatory diseases. [europepmc]
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