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MiR-495 regulates macrophage M1/M2 polarization and insulin resistance in high-fat diet-fed mice via targeting FTO

  • Fang Hu
  • Jingkai Tong
  • Bangli Deng
  • Jia Zheng
  • Chengzhi LuEmail author
Molecular and cellular mechanisms of disease
Part of the following topical collections:
  1. Molecular and cellular mechanisms of disease

Abstract

MicroRNA 495 (miR-495) has been discovered to be involved in the metabolism and immune response in human body. The purpose of this study was to investigate the effect of miR-495 on macrophage M1/M2 polarization and insulin resistance in type 2 diabetes (T2D). A T2D mouse model was established by feeding C57BL/6 mice with a high-fat diet (HFD). The expressions of M1/M2 polarization markers and miR-495 in peritoneal macrophages were determined by qRT-PCR or Western blot. Mouse insulin tolerance test (ITT) and glucose tolerance test (GTT) were performed, and the targeted binding effect between miR-495, fat mass, and obesity-associated gene (FTO) was verified by double luciferase gene reporter assay. The body weight, blood glucose content, and miR-495 expression in macrophages of the HFD group were remarkably higher than those of the normal diet (ND) group. Besides, miR-495 induced the transformation of macrophages into M1-type pro-inflammatory macrophages and enhanced the insulin resistance of T2D mice. More importantly, FTO was proved to be a direct target gene of miR-495 and silencing FTO could induce the transformation of macrophages into M1-type pro-inflammatory macrophages. These results demonstrated that miR-495 could promote the transformation of macrophages into M1-type pro-inflammatory macrophages by inhibiting the expression of its target gene FTO, and aggravate the insulin resistance and adipose tissue inflammation in T2D mice, which provided a certain theoretical basis for the targeted treatment of T2D.

Keywords

High-fat diet Type 2 diabetes miR-495 FTO Macrophage M1/M2 polarization 

Notes

Authors’ contributions

FH: study concepts, study design, literature research, experimental studies, manuscript preparation and editing; JKT: literature research experimental studies, manuscript preparation, and editing; BLD: experiments work, data acquisition, statistical analysis, and manuscript writing; JZ: data acquisition, statistical analysis, and clinical study; CZL: study concepts, definition of intellectual content, study design, data analysis, and manuscript review. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Research involving Animals

Ethical approval was obtained from the Ethics Committee of Tianjin First Central Hospital. All procedures performed in studies involving animals were conducted in accordance with the animal care and guidelines of Tianjin First Central Hospital.

Informed consent

Not applicable.

Supplementary material

424_2019_2316_Fig5_ESM.png (79 kb)
Supplementary figure S1

Measurement of body weight, blood glucose, and miR-495 expression in peritoneal macrophages in mouse. (A) Comparison of body weight of mice in each group after 12 weeks of ND or HFD feeding. (B) Measurement of blood glucose changes at different time points by GTT. (PNG 79 kb)

424_2019_2316_MOESM1_ESM.tif (224 kb)
High resolution image (TIF 223 kb)
424_2019_2316_Fig6_ESM.png (68 kb)
Supplementary figure S2

Measurement of body weight at 4w and 16w. (A) Body weight of mice of ND and HFD groups at 4w and 16w. (B) Body weight of mice of miR-495 scramble and miR-495 inhibitor groups at 4w and 16w. (PNG 68 kb)

424_2019_2316_MOESM2_ESM.tif (224 kb)
High resolution image (TIF 224 kb)
424_2019_2316_Fig7_ESM.png (248 kb)
Supplementary figure S3

Summary of results obtained in this study. (PNG 247 kb)

424_2019_2316_MOESM3_ESM.tif (307 kb)
High resolution image (TIF 307 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Fang Hu
    • 1
  • Jingkai Tong
    • 2
  • Bangli Deng
    • 3
  • Jia Zheng
    • 1
  • Chengzhi Lu
    • 1
    Email author
  1. 1.Department of CardiologyTianjin First Central HospitalTianjinChina
  2. 2.Department of EndocrinologyTianjin First Central HospitalTianjinChina
  3. 3.Clinical Laboratory of Metabolic Diseases Hospital of Tianjin Medical UniversityTianjinChina

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