Assessment of the relationship between adiposity, Sirtuin 1 and miR-30a-5p in a mixed-ancestry population in Bellville South, Cape Town.

Abstract

The steadily increasing rise in obesity and metabolic disorders is a global problem that requires in depth understanding of the molecular mechanisms underlying adiposity. This study assessed the regulatory relationship between miR-30a-5p, sirtuin 1 (SIRT1) and adiposity in a mixed-ancestry population from Bellville South and Belhar, Cape Town, South Africa. The study analysed samples from 300 participants grouped into three body mass index (BMI) categories: normal-weight, overweight and obese. The groups were further classified by waist circumference (WC) as either normal or high. The study aimed to determine whether miR-30a-5p expression was affected by adiposity and its regulatory impact on SIRT1. SIRT1 concentration, SIRT1 expression, and miR-30a-5p expression were measured from whole blood and serum samples using enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR). Statistical analysis included Spearman’s correlation to assess relationships between the variables, logistic regression models for differences between miR-30a-5p and SIRT1 expression across BMI and WC categories. Finally, receiver operating characteristic (ROC) curves were generated and the area under the curve (AUC) analysed to determine whether either miR-30a- 5p, SIRT1 or both are predictors of elevated BMI or high WC. p-values less than 0.05 were considered statistically significant. The study findings demonstrated that miR-30a-5p was significantly higher in the overweight and obese participants when compared to the normal weight participants which supports its role in adipogenesis. In contrast, SIRT1 concentration levels tended to decrease with obese participants, which aligns with the hypothesis of SIRT1 repression by miR-30a-5p. Interestingly, SIRT1 expression tended to increase in obese and high WC when compared to normal-weight and normal WC. This suggests post-transcriptional regulation of SIRT1 by miR-30a-5p. Comprehending the relationship between miR-30a-5p and SIRT1 in human adiposity provides novel insights into the molecular pathways involved in obesity development and points to miR-30a-5p as a potential biomarker and therapeutic target for metabolic regulation. The study findings contribute to the understanding of epigenetic regulation in obesity and suggest pathways for targeted intervention in populations with high obesity prevalence, such as South Africa's mixed-ancestry community.