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Article: Adipocyte-secreted Exosomal Microrna-34a Inhibits M2 Macrophage Polarization To Promote Obesity-induced Adipose Inflammation

TitleAdipocyte-secreted Exosomal Microrna-34a Inhibits M2 Macrophage Polarization To Promote Obesity-induced Adipose Inflammation
Authors
KeywordsAdipose tissue
Inflammation
Macrophages
Metabolism
Obesity
Issue Date2019
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal of Clinical Investigation, 2019, v. 129 n. 2, p. 834-849 How to Cite?
AbstractPersistent, 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.
Persistent Identifierhttp://hdl.handle.net/10722/273930
ISSN
2019 Impact Factor: 11.864
2015 SCImago Journal Rankings: 8.764
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorPan, Y-
dc.contributor.authorHui, X-
dc.contributor.authorHoo, RLC-
dc.contributor.authorYe, D-
dc.contributor.authorChan, CYC-
dc.contributor.authorFeng, T-
dc.contributor.authorWang, Y-
dc.contributor.authorLam, KSL-
dc.contributor.authorXu, A-
dc.date.accessioned2019-08-18T14:51:34Z-
dc.date.available2019-08-18T14:51:34Z-
dc.date.issued2019-
dc.identifier.citationJournal of Clinical Investigation, 2019, v. 129 n. 2, p. 834-849-
dc.identifier.issn0021-9738-
dc.identifier.urihttp://hdl.handle.net/10722/273930-
dc.description.abstractPersistent, 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.-
dc.languageeng-
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org-
dc.relation.ispartofJournal of Clinical Investigation-
dc.subjectAdipose tissue-
dc.subjectInflammation-
dc.subjectMacrophages-
dc.subjectMetabolism-
dc.subjectObesity-
dc.titleAdipocyte-secreted Exosomal Microrna-34a Inhibits M2 Macrophage Polarization To Promote Obesity-induced Adipose Inflammation-
dc.typeArticle-
dc.identifier.emailPan, Y: panicy@hku.hk-
dc.identifier.emailHui, X: hannahui@hku.hk-
dc.identifier.emailHoo, RLC: rubyhoo@hkucc.hku.hk-
dc.identifier.emailFeng, T: tsfeng@hku.hk-
dc.identifier.emailWang, Y: yuwanghk@hku.hk-
dc.identifier.emailLam, KSL: ksllam@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.authorityHui, X=rp02250-
dc.identifier.authorityHoo, RLC=rp01334-
dc.identifier.authorityWang, Y=rp00239-
dc.identifier.authorityLam, KSL=rp00343-
dc.identifier.authorityXu, A=rp00485-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1172/JCI123069-
dc.identifier.pmid30667374-
dc.identifier.pmcidPMC6355214-
dc.identifier.scopuseid_2-s2.0-85060874612-
dc.identifier.hkuros301589-
dc.identifier.volume129-
dc.identifier.issue2-
dc.identifier.spage834-
dc.identifier.epage849-
dc.publisher.placeUnited States-

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