Circulating microRNA (miRNA) are post-transcriptional modulators of gene expression with potential use as risk prediction biomarkers for metabolic alterations(Reference Faccini, Ruidavets and Cordelier1). Recent evidence shows that members of the let-7 family of miRNA are critically involved in inflammation(Reference Law, Lee and Hsu2), hypertension(Reference Faccini, Ruidavets and Cordelier1), coronary artery disease(Reference Faccini, Ruidavets and Cordelier1) and atherosclerosis(Reference Faccini, Ruidavets and Cordelier1). Consequently, the objective of this study was to investigate the relationship between circulating miR-let-7c, measures of adiposity, lipid profile and inflammatory state in adults. This study analysed 192 individuals, aged 20–59 years, mean body mass index: 26.3 kg/m2 (95% CI: 25.44, 27.15) from 2015 ISA-Nutrition survey(Reference Fisberg, Sales and Fontanelli3), a household cross-sectional, population- based survey of residents from the urban area of São Paulo, Brazil. Participants did not have major systematic disease as acute inflammatory or thyroid diseases; cancer; use of antibiotics, anti- inflammatory, immunomodulators, antiretrovirals; chronic alcoholism; or were pregnant/lactating women. Plasma IL-1β, IL-6, IL-10, TNF-α, monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), adiponectin and leptin concentrations were determined by immunoassays.
Plasma C-reactive protein was quantified by enzyme-linked immunosorbent assay. The expression of miR-let-7c-5p in plasma was assessed by RT-qPCR, and Spike-in cel-miR-39 and UniSp6 were used as reference controls for normalisation. Relative miRNA expression was calculated using the 2−ΔΔCT method. The Stata somersd module was used to calculate confidence intervals for Kendall's tau-a to estimate correlations between miR-let-7c and anthropometric, lipid and inflammatory variables (Stata, version 17.0, StataCorp). Most participants had raised waist circumference (67.7%) (≥ 80 cm for women or ≥ 90 cm for men), low HDL-c concentrations (51.1%) and high LDL-c concentrations (52.1%), and approximately 30% had increased plasma triacylglycerol concentrations. miR-let-7c expression was positively correlated with both body weight (tau-a: 0.13; 95% CI: 0.02, 0.25) and waist circumference (tau-a: 0.11; 95% CI: 0.00, 0.22) (P < 0.05). In addition, miR-let-7c expression correlated positively with triacylglycerol (tau-a: 0.25; 95% IC: 0.15, 0.36; P < 0.001), total cholesterol (tau-a: 0.11; 95% IC: 0.00, 0.22; P < 0.05) and non-HDL-c (tau-a: 0.16; 95% IC: 0.06, 0.27; P < 0.01) concentrations and negatively with HDL-c concentration (tau-a: -0.16; 95% IC: -0.26, -0.06; P < 0.01). No significant relationship was found with LDL-c concentration. miR-let-7c expression also correlated positively with PAI-1 (tau-a: 0.17; 95% IC: 0.06, 0.28; P < 0.01) and negatively with both adiponectin (tau-a: -0.13; 95% IC: -0.23, -0.04; P < 0.01) and VCAM-1 (tau-a: -0.12; 95% IC: -0.22, -0.02; P < 0.05). There were no significant correlations between miRNA expression and the other measured inflammatory biomarkers. In conclusion, this study provides evidence that miR-let-7c expression in plasma is related to cardiometabolic risk through relationships with a proinflammatory state, abnormal blood lipid concentrations, excess body weight and abdominal adiposity.
Acknowledgments
This work was supported by the São Paulo Research Foundation - FAPESP (Grant 2021/10940-7| Grant 2020/03104-5); National Council for Scientific and Technological Development – CNPq (Grant 150834/2020-9).
