Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 14, Issue 11, Pages 1599-1609Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.26274
Keywords
obesity; miR27a; inflammation; preadipocytes; 3T3 cells; macrophage-like
Categories
Funding
- National Natural Science Foundation of China [81570762]
- Preclinical Pharmacology R&D Center of Jilin Province [20170623062TC, 20180201025YY]
- Eduction Department of Jilin Province [JJKH20180247KJ]
- Norman Bethune Program of Jilin University [2015224]
- Heart and Stroke Foundation of Canada
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Recruitment and polarization of classically activated (M1) macrophages within adipose tissue contribute tochronic low-grade inflammation in obesity. Adipose tissue precursor cells exhibit the capacity to develop macrophage-like characteristics and adipocyte-derived miR27a is known to promote reprogramming of somatic cells. It was unknown whether exogenous addition of miR27a promote the development of macrophage-like characteristics of adipose precursor cells. We examined macrophage surface antigen, phagocytosis and migration ability in 3T3-L1 preadipocytes transfected with miR27a mimics. Transfection of 3T3-L1 preadipocytes with miR27a mimics increased phagocytosis and migration and increased the number of cells expressing the macrophage makers F4/80 and MHC compared to controls. M2 and CD206 macrophage markers were unaltered. In addition, transfection of 3T3-L1 preadipocytes with miR27a mimics reduced PPAR. expression, activated NF-kappa B and promoted secretion of the inflammatory cytokines MCP-1, TNF-alpha and IL-1 beta compared to controls. The level of anti-inflammatory factors Arg-1, IL-10, Ym1 and Fizz1 were unaltered. Secretion of miR27a was increased in conditioned medium prepared from palmitic acid-treated differentiated 3T3-L1 adipocytes compared to controls. Incubation of 3T3-L1 preadipocytes with this conditioned medium increased phagocytosis and migration compared to controls. Finally, conditioned medium prepared from differentiated 3T3-L1 adipocytes transfection with miR27a inhibitors reduced phagocytosis and migration in 3T3-L1 preadipocytes compared to controls. The data indicate that PPAR. agonists may reverse the activation of NF-kappa B pathway mediated by miR27a overexpression and reduce phagocytosis and migration of adipose precursor cells. In addition, miR27a may promote the development of macrophage-like characteristics in 3T3-L1 preadipocytes.
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