Endocrine Abstracts

Aim: Obesity represents a risk factor for the development of type 2 diabetes mellitus (T2DM). Although, this seems to reflect common environmental and genetic factors underlying both pathologies, the link between these conditions is not so clear. A diverse group of elements, including miRNAs, has been implicated in the development of these two metabolic diseases. miRNAs are involved in complex regulatory networks of gene expression. This suggests that alterations in their expression levels, their cellular location, and their action may have far-reaching effects on cellular physiology and even invoke sustained alterations. Thus, the main objective of this pilot study is to establish if the differential miRNA expression profile in patients diagnosed with obesity are associated with the presence of T2DM.

Materials and methods: miRNA-seq technology (NGS) was applied to sequence the miRNA profile of visceral adipose tissue (VAT) (n = 6) and paired skeletal muscle tissue (SMT) (n = 6) of obese women which underwent bariatric surgery, with and without T2DM. To establish the miRNA expression pattern in the different tissues analyzed, miRDeep2 software was used. Differentially expressed miRNAs analyses were performed with edgeR. Prediction of target genes of the miRNAs was established using the TargetScan program. Statistical computing was performed in R environment.

Results: After sequencing was performed, patients with T2DM were compared to those without it. Expression analysis revealed 95 (61 up and 34 downregulated) differentially expressed miRNA out of 807 (11.77%) in VAT and 40 (16 up and 24 downregulated)out of 663 miRNAs (6.03%) in SMT. Besides Principal Analysis Component didn’t showed a clear separation between groups. Despite this, GOrilla tool was used to identify the biological processes that could be altered. Biological processes upregulated in the SMT of obese patients with T2DM were involved in cell migration, signal transduction or regulation of metabolic processes. Downregulated pathways were mainly related to negative regulation of transcription mechanisms and macromolecule biosynthesis. Otherwise, biological processes implicated in covalent chromatin modification were upregulated in VAT of T2DM obese individuals. Interestingly, in VAT, downregulated miRNAs identified were significantly enriched in pathways related to glucose response. Some genes that appeared in this last category were: PPARGC1A, PDK3, LIN28A, ACVR1C.

Conclusions: Patients with obesity and T2DM have a differential miRNA profile in those tissues associated with insulin resistance compared to those that are not. Further studies will be necessary to analyse the genes and routes actually involved in the development of T2DM.