Abstract
Due to increasing prevalence of obesity, a simple method or methods for the diagnosis of metabolic syndrome are urgently required to reduce the risk of associated cardiovascular disease, diabetes and cancer. This study aimed to identify a miRNA biomarker that may distinguish metabolic syndrome from obesity and to investigate if such a miRNA may have functional relevance for metabolic syndrome.52 adults with clinical obesity (n=26) or metabolic syndrome (n=26) were recruited. Plasma specimens were procured from all and were randomly designated to discovery and validation cohorts. miRNA discovery profiling was performed, using array technology, on plasma RNA. Validation was performed by quantitative polymerase chain reaction. The functional effect of miR-758-3p on its predicted target, cholesterol efflux regulatory protein/ATP-binding cassette transporter, was investigated using HepG2 liver cells.Custom miRNA profiling of 25 miRNAs in the discovery cohort found miR-758-3p to be detected in the obese cohort but undetected in the metabolic syndrome cohort. miR-758-3p was subsequently validated as a potential biomarker for metabolic syndrome by quantitative polymerase chain reaction. Bioinformatics analysis identified cholesterol efflux regulatory protein/ATP-binding cassette transporter as miR-758-3p’s predicted target. Specifically, mimicking miR-758-3p in HepG2 cells suppressed cholesterol efflux regulatory protein/ATP-binding cassette transporter protein expression; conversely, inhibiting miR-758-3p increased cholesterol efflux regulatory protein/ATP-binding cassette transporter protein expression.miR-758-3p holds potential as a blood-based biomarker for distinguishing progression from obesity to metabolic syndrome and as a driver in controlling cholesterol efflux regulatory protein/ATP-binding cassette transporter expression, indicating it potential role in cholesterol control in metabolic syndrome.
Highlights
Metabolic Syndrome (MetS) is an ever-increasing concern worldwide due to the increase in obesity and sedentary lifestyles
Obesity is fundamental to MetS as it appears to precede the emergence of the other MetS risk factors [5]
We progressed to investigate the potential use of blood-based miRNAs as biomarkers for metabolic syndrome (MetS) and the putative ability of miRNAs in the peripheral circulation to discriminate progression from obesity to MetS [3]
Summary
Metabolic Syndrome (MetS) is an ever-increasing concern worldwide due to the increase in obesity and sedentary lifestyles. It is estimated that one quarter of the adult population has MetS [1]. MetS culminates from the clustering of component risk factors including obesity [6]. Individuals with MetS are five times more likely to develop Type 2 diabetes (T2DM) and three times more likely to suffer from cardiovascular disease (CVD) [7]. The development of many cancer types is associated with obesity and MetS. As the prevalence of MetS is increasing, the prevalence of these conditions is increasing in parallel. Accurate and timely diagnosis of MetS is, of critical importance to avoid this increased risk
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