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

Ayo P Doumatey,Charles N Rotimi,Lin Lei,Amadou Gaye,Jie Zhou,William J He,Adebowale Adeyemo,Gary H Gibbons

doi:10.1038/s41598-018-26065-5

Abstract

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.

Highlights

Obesity is characterised by excessive fat accumulation that is mostly the result of excess energy intake relative to levels of physical activity[1]
Their lipid, inflammatory and glycolytic profiles were in the normal ranges whereas metabolically abnormal individuals with obesity (MAO) group had higher triglycerides/high density lipoprotein-cholesterol (TG/HDL-C) ratio and C-reactive protein (CRP) compared to the metabolically healthy individuals with obesity (MHO) group
We identified 8 differentially expressed Micro-ribonucleic acids (miRNAs) (DEMs) between MHO and MAO (p

Summary

Introduction

Obesity is characterised by excessive fat accumulation that is mostly the result of excess energy intake relative to levels of physical activity[1]. It has been shown that a subset of healthy obese individuals remain healthy into their elderly years, as MHO do not have a higher risk of all-cause mortality when compared to their normal weight counterparts[10]. Understanding this subgroup of obesity at the molecular and cellular level www.nature.com/scientificreports/. Because MHO individuals are suspected of being in a transitional phase between healthy normal weight and MAO8,9, understanding the differences between the miRNA profiles of MHO and MAO can shed light on the importance of miRNA regulation in the development of obesity-associated metabolic disorders. We investigated the serum expression levels of a panel of 179 miRNAs to determine differential expression patterns in the miRNA profile of MHO and MAO individuals

Methods

Results

Conclusion