Characterization of Differentially Expressed Circulating miRNAs in Metabolically Healthy versus Unhealthy Obesity.

Susana Rovira-Llopis,Carlos Morillas,Víctor M Victor,Milagros Rocha,Rubén Díaz-Rúa,Joaquín Panadero-Romero,Zaida Abad-Jimenez,Celia Bañuls,Neus Bosch-Sierra,Carmen Grau-Del Valle,Francesca Iannantuoni

doi:10.3390/biomedicines9030321

Abstract

Obese individuals without metabolic comorbidities are categorized as metabolically healthy obese (MHO). MicroRNAs (miRNAs) may be implicated in MHO. This cross-sectional study explores the link between circulating miRNAs and the main components of metabolic syndrome (MetS) in the context of obesity. We also examine oxidative stress biomarkers in MHO vs. metabolically unhealthy obesity (MUO). We analysed 3536 serum miRNAs in 20 middle-aged obese individuals: 10 MHO and 10 MUO. A total of 159 miRNAs were differentially expressed, of which, 72 miRNAs (45.2%) were higher and 87 miRNAs (54.7%) were lower in the MUO group. In addition, miRNAs related to insulin signalling and lipid metabolism pathways were upregulated in the MUO group. Among these miRNAs, hsa-miR-6796-5p and hsa-miR-4697-3p, which regulate oxidative stress, showed significant correlations with glucose, triglycerides, HbA1c and HDLc. Our results provide evidence of a pattern of differentially expressed miRNAs in obesity according to MetS, and identify those related to insulin resistance and lipid metabolism pathways.

Highlights

Obesity is characterized by numerous deleterious metabolic effects and increased cardiovascular risk
The metabolically unhealthy obese (MUO) group displayed higher glucose (p < 0.001), HbA1c (p < 0.01), insulin and HOMA-IR levels (p < 0.01), indicating hyperglycaemia and insulin resistance. High-sensitive C-reactive protein (hsCRP) levels were similar in both groups
MUO-upregulated miRNAs involved in insulin signalling and lipid metabolism pathways we identified those that are associated with modulation of oxidative stress

Summary

Introduction

Obesity is characterized by numerous deleterious metabolic effects and increased cardiovascular risk. In some individuals, these effects are negligible or not present at all, and such cases are referred to as metabolically healthy obese (MHO). There is no consensus regarding the definition of metabolically healthy obesity, but this subset of obese subjects is usually characterized by a lower waist circumference, better physical fitness, preserved insulin sensitivity, and a low prevalence of metabolic risk factors, despite their high body mass index (BMI) [1,2]. Obesity is known to be the result of environmental and genetic factors. In addition to genetic susceptibility, epigenetics and gene–environment interaction contribute to the appearance of obesity [5].

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Conclusion