Abstract
Aims/IntroductionMetformin, a widely prescribed antidiabetic agent, has been shown to exhibit anti‐inflammatory effects in obese and type 2 diabetes patients, but the mechanism is not well elucidated. Microribonucleic acids (miRNAs) are a group of small non‐coding ribonucleic acids that participate in many biological and pathological processes. The aim of the present study was to investigate whether Dicer, a key miRNA biogenesis enzyme, and miRNAs in macrophages are implicated in the anti‐inflammatory effects of metformin.Materials and MethodsEnzyme‐linked immunosorbent assay and reverse transcription quantitative polymerase chain reaction were carried out to verify the anti‐inflammatory effects of metformin. miRNA microarray was applied to detect the expression profile of miRNA. Western‐blotting, enzyme‐linked immunosorbent assay and reverse transcription quantitative polymerase chain reaction were used to examine the role Dicer and miRNAs play in the anti‐inflammatory effects of metformin.ResultsIn parallel with the suppression of interleukin‐6 and tumor necrosis factor‐α production in resting and lipopolysaccharide‐stimulated macrophages, metformin could induce an increase in Dicer and most miRNAs. When Dicer was knocked down, the anti‐inflammatory effects of metformin were significantly attenuated. Additionally, the upregulation of miRNA (miR)‐34a‐5p and miR‐125b‐5p by metformin were also blunted in Dicer knockdown macrophages. Furthermore, inhibition of miR‐34a‐5p and miR‐125b‐5p could impair the suppressive action of metformin on pro‐inflammatory factors production, whereas overexpression of the two miRNAs mimicked the anti‐inflammatory effects of metformin.ConclusionsMetformin might show anti‐inflammatory effects in macrophages through the induction of Dicer and the subsequent upregulation of miR‐34a‐5p and miR‐125b‐5p.
Highlights
Obesity can induce insulin resistance and is one of the important hazards for type 2 diabetes[1]
Metformin inhibits IL-6 and tumor necrosis factor (TNF)-a production in macrophages we confirmed the anti-inflammatory effects of metformin in murine macrophages
As the microarray only showed that metformin altered the Microribonucleic acids (miRNAs) expression in resting macrophages, we investigated whether metformin regulates miRNA levels in LPS-stimulated macrophages
Summary
Obesity can induce insulin resistance and is one of the important hazards for type 2 diabetes[1]. Obesity-induced insulin resistance is closely associated with chronic inflammatory in adipose tissue[2], which is partly mediated by infiltrating immune cells and the released inflammatory factors[3]. Received 17 January 2019; revised 26 April 2019; accepted 14 May 2019 immune cells, adipose tissue macrophages (ATMs) act as important players in obesity-associated low-grade inflammation[4]. Obesity could induce a phenotypic change in ATMs polarization. ATMs are mostly composed of alternatively activated macrophages, which produce anti-inflammatory factors, such as interleukin (IL)-10, arginase and IL-1 receptor antagonist. The majority of ATMs are polarized towards a classically activated state
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