The expression levels of SIRT1 splicing isoforms and genes regulating mitochondrial homeostasis in the liver of patients with type 2 diabetes mellitus and obesity

Aim. To evaluate the association between the expression levels of sirtuin 1 (SIRT1) splicing isoforms and the genes associated with mitochondrial homeostasis (PGC-1α, PPAR-γ, PPAR-α, TFAM, MFN2, OPA1, and DRP1) in the liver of patients with type 2 diabetes mellitus (T2DM).
Materials and methods. The study included 59 patients who were divided into two groups: 1) control group, body mass index (BMI) < 30 kg/m2, without cardio-metabolic disorders; 2) patients with T2DM, BMI > 30 kg/m2. A biochemical analysis of the patients’ blood parameters was performed, and the expression level of the genes of interest in the liver tissue was studied using quantitative RT-PCR.
Results. It was found that the SIRT1 splicing isoforms V1, V2, and V3 were stably expressed in the liver of patients with T2DM. SIRT1 isoforms occur not only individually, but also in various combinations. The expression of the SIRT1 V3 isoform was significantly increased in the group of patients, while the remaining analytes did not significantly differ between the groups. The SIRT1 V3 isoform positively correlated with glucose levels. It is worth noting that the total SIRT1 did not show significant correlations with the genes of interest and biochemical parameters, which only confirms the need to study the expression of isoforms separately.
Conclusion. SIRT1 isoforms were stably expressed in the liver, and the expression level of SIRT1 V3 isoform was significantly higher in patients with T2DM. The results of this work can serve as a basis for further studies of interactions between SIRT1 splicing isoforms and mitochondrial homeostasis proteins at the post-translational level.

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