Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.

Insulin resistance (IR) is a key contributor to the development of metabolic diseases, and metformin has been shown to help mitigate IR. Long non-coding RNAs (lncRNAs) are emerging as important regulators in metabolic disorders. This study aimed to investigate the differential expression of lncRNAs in IR and assess the impact of metformin on these lncRNAs. Using the Huh7 cell line to model IR (Huh7-IR), we treated the cells with metformin (Huh7-IR+Metf). Microarray analysis, followed by bioinformatic analysis in RStudio, identified 127 downregulated and 109 upregulated lncRNAs, among which 60 showed reduced expression following metformin treatment in Huh7-IR cells. Notably, the upregulated lncRNAs HOX transcript antisense RNA (HOTAIR), long intergenic non-protein coding RNA, muscle differentiation 1 (LINCMD1) and Prader-Willi region non-protein coding RNA 2 (PWRN2) were found to be associated with genes involved in the insulin signaling pathway. These three lncRNAs were further validated using real-time RT-PCR. This study highlights the differential expression of lncRNAs in IR and their modulation by metformin. Specifically, metformin restores the expression of lncRNAs that were deregulated in IR, including HOTAIR, LINCMD1, and PWRN2, likely through the regulation of critical biological processes and signaling pathways associated with IR. In conclusion, our findings demonstrate that metformin modulates the expression of key lncRNAs, including HOTAIR, LINCMD1, and PWRN2, which are deregulated in insulin resistance. This regulation likely occurs through the modulation of critical signaling pathways, such as NFκB and AMPK, suggesting that targeting lncRNAs could offer new therapeutic avenues for managing IR and related metabolic disorders.