Negative correlation between microRNA and insulin sensitivity gene expression in adipose tissue with potential implications for diabetes and neurodegenerative diseases

Adipose tissue-derived microRNAs are recognized as key players in the development of obesity-related complications. The aim of this study was to investigate whether the expression of genes critical for both insulin sensitivity and neuronal metabolism ( APP , SOCS3 , PTPN1 , PTPN2 ) is altered by microRNA interference in adipose tissue of obese patients, predisposing them to the development of metabolic inflammation and possibly cognitive decline. The expression of mRNAs of the above-mentioned genes, selected adipokines and microRNAs was measured by real-time PCR in adipose tissue of 75 obese patients, 19 patients after metabolic surgery and 25 normal weight subjects. mRNA levels of genes promoting insulin sensitivity: APP and PTPN2 were significantly (p < 0.05) decreased in adipose tissue of obese patients, whereas SOC3 and PTPN1 (associated with insulin resistance and metabolic inflammation, respectively) were increased. We also observed significant positive correlations between the mRNA levels of these genes and the expression of adipokines (interleukins 1B, 6, 15, TNFα, resistin, adiponectin). Finally, we analyzed the levels of microRNAs targeting the mRNAs of the genes studied and found several negative correlations between their expression, suggesting that these microRNAs may be involved in the regulation of insulin sensitivity in adipose tissue.