title: Adipogenic miR-27a in adipose tissue upregulates macrophage activation via inhibiting PPARγ of insulin resistance induced by high-fat diet-associated obesity.
abstract: Chronic low degree inflammation caused by macrophage activation is a crucial factor underlying insulin resistance induced by obesity. To illustrate the mechanism of regulating of macrophage activation in adipose tissue, the role of adipogenic miR-27a activating M1 macrophage polarization via blocking PPARγ was evaluated. Obese mice model and miR-27a overexpression or knockdown mice model were established and related biochemical index were examined. Raw264.7 and 3T3-L1 were cultured and co-cultured for mimicking the microenvironment of local inflammation. Macrophage infiltration was observed. MiR-27a and cytokines levels in serum and adipose tissue were measured. Macrophage polarization markers and protein expression in insulin or inflammatory signaling pathways were observed. Impaired glucose tolerance and insulin tolerance was observed in 4w, 8w and 12w of high fat diet and miR-27a overexpression mice. Concurrently, miR-27a was increased in serum in a time-dependent manner, along with M1 cytokines and M1 macrophages increasing in adipose tissue clearly. Insulin signaling pathway was blocked, and PPARγ was suppressed. However, NF-κB was activated. On the other hand, activated macrophages and hypertrophic adipocytes induced by miR-27a could increase the ratio of Raw264.7 migration, including improving cytokines generation, and blocking PPARγ expression markedly. The present studies are conducted to clarify that miR-27a has increased along with up-regulation in the process of proinflammatory cytokines generation, macrophage influx and M1 macrophage polarization in obesity. These indicate that miR-27a gives the novel target of intervention for inflammation and insulin resistance in obesity.
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yao
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Linjing
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Junnan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Meishuang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Lan
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Yilun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Guan
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China. Electronic address: zhangming_00@126.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; School of Nursing, Jilin University, Changchun 130021, China. Electronic address: chen_lab@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D059305:Diet, High-Fat / Q000009:adverse effects*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007333:Insulin Resistance; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D035683:MicroRNAs / Q000235:genetics*; D009765:Obesity / Q000139:chemically induced* / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000067996:RAW 264.7 Cells
chemical_list: D016207:Cytokines; D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse; D047495:PPAR gamma
keywords: Insulin resistance; Macrophage polarization; MiR-27a; Obesity; PPARγ