Circulating MiR-374a-5p is a potential modulator of the inflammatory process in obesity

Sci Rep. 2018 May 16;8(1):7680. doi: 10.1038/s41598-018-26065-5.


Obese individuals without expected metabolic co-morbidities are referred to as metabolically healthy obese (MHO). The molecular mechanisms underlying this phenotype remain elusive. MicroRNAs may be involved in the MHO phenotype. To test this hypothesis, we screened 179 serum miRNAs in 20 African-American women (10 MHOs and 10 metabolically abnormal obese individuals -MAO). We identified 8 differentially expressed miRNAs (DEMs) with validation in an independent sample of 64 MHO and 34 MAO. Of the eight DEMs in the screening phase (p ≤ 0.05), miR-374a-5p remained significant (p = 0.04) with directional consistency in the validation sample. Ingenuity Pathway analysis revealed that miR-374a-5p putatively targeted 37 mRNAs (e.g. chemokines and transcription factors) which are members of canonical pathways involved in inflammation (IL-17A signaling) and lipid metabolism. Analysis restricted to adipocytes, the main source of circulating miRNAs in obesity, identified 3 mRNAs (CCL2, STEAP2, EN1) as the main target of miR-374a-5p. Evaluation of the 3 mRNAs in an independent sample showed that CCL2 was significantly downregulated (p = 0.0005). In summary, MiR-374a-5p is upregulated in MHO compared to MAO individuals and appears to show association with downregulation of pro-inflammatory markers that are linked to insulin resistance. Given the correlative nature of our findings, functional studies are needed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Cell Cycle Proteins
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Cohort Studies
  • Female
  • Gene Expression Regulation*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Inflammation / blood
  • Inflammation / etiology*
  • Inflammation / pathology
  • Insulin Resistance*
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Obesity / complications*
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Oxidoreductases
  • Signal Transduction
  • Young Adult


  • Biomarkers
  • CCL2 protein, human
  • Cell Cycle Proteins
  • Chemokine CCL2
  • EN1 protein, human
  • Homeodomain Proteins
  • MIRN374 microRNA 374, human
  • MicroRNAs
  • Oncogene Proteins
  • Oxidoreductases
  • STEAP3 protein, human