Promising approaches to the treatment of obesity include increasing energy expenditure and slowing down fibrogenesis of adipose tissue. The neurotransmitter reuptake inhibitor sibutramine affects appetite and activates lipolysis in a catecholaminergic way. MicroRNAs (miRs) are considered as biomarkers of molecular genetic mechanisms underlying various processes. The profile of a number of miRs is altered in obesity, both in the circulation and in adipose tissue. The aim of this study was to assess the expression levels of miRs (hsa-miR-378a-3p, hsa-miR-142-3p) by real-time polymerase chain reaction in subcutaneous adipose tissue (SAT) and in plasma in patients with different degrees and duration of obesity and during sibutramine therapy. This study included 51 obese patients and 10 healthy subjects with normal weight who formed a control group. The study found that, before treatment, obese patients had no significant difference in the expression level of miR-378 in SAT and plasma compared to the control group, while the expression of miR-142 was significantly decreased in SAT and increased in plasma. A significant elevation in miR-378 expression level was noted in patients with first-degree obesity and duration of less than 10 years, and the decline in miR-142 increased with the duration of obesity. These data indicate a maximal increase in the expression of the adipogenesis inducer miR-378 in the early stages of obesity, a progressive decrease in the expression of the fibrogenesis inhibitor miR-142 in SAT with growth of duration of obesity and the likely presence of antifibrogenic effects of sibutramine realized through miR-142 activation.

Mutations in the LMNA gene resulting in the substitution of the highly conserved arginine 482 residue in the globular C-terminal domain of lamin A/C are associated with the Dunnigan-type familial...

Objective. To study the association of genetic determinant (A-risk allele of rs9939609 SNP of FTO gene) with prevalence of metabolic syndrome (MS) and its components in residents of different Russian cities.Design and methods. We examined 425 patients with MS or its components from different cities of Russia (St Petersburg, Kursk, Kaliningrad), stratiied by sex and age [175 male (41,2 %) and 250 female (58,8 %), mean age — 47,2 ± 0,6 years]. All subjects were interviewed with special questionnaire. Physical examination included anthropometry (waist and hip circumferences, weight, height), blood pressure and heart rate registration. MS was deined according to NCEP-ATPIII as well as IDF (2005) and JIS (2009) criteria. Fasting plasma lipids and glucose were performed in all patients by Hitachi-902 equipment (Roche reagents). Genomic deoxyribonucleic acid (DNA) was puriied from peripheral blood lymphocytes and genotyping was performed using real time polymerase chain reaction method by allele-speciic probes (Applied Biosystems).Results. Among males with AA genotype waist and hip circumferences and weight were higher, compared to subjects with TA and TT genotypes (p = 0,0002, p = 0,001 and p = 0,01, respectively). There was a tendency to the increase of body mass index (BMI) in the group with AA genotype compared to subjects with TA and TT genotypes (29,7 ± 0,7; 27,6 ± 0,4 and 27,9 ± 0,3 kg/m², respectively, р = 0,1). In our study AA genotype was associated with higher glucose level compared to TA and TT genotypes (5,6 ± 0,2; 5,0 ± 0,1 and 5,1 ± 0,1 mmol/l, respectively, p = 0,04). There was a tendency to the increase of the proportion of hypertensives among patients with AA genotype compared to TA and TT genotypes (70,5; 65,2 and 57 %, respectively, p = 0,18).Conclusion. In Russian population FTO genepolymorphism rs9969309 is associated not only with abdominal obesity, but also with other components of MS, including hyperglycemia and hypertension.

Obesity and type 2 diabetes mellitus (T2DM) are often combined and pathologically affect many tissues due to changes in circulating bioactive molecules. In this work, we evaluated the effect of blood plasma from obese (OB) patients or from obese patients comorbid with diabetes (OBD) on skeletal muscle function and metabolic state. We employed the mouse myoblasts C2C12 differentiation model to test the regulatory effect of plasma exposure at several levels: (1) cell morphology; (2) functional activity of mitochondria; (3) expression levels of several mitochondria regulators, i.e., Atgl, Pgc1b, and miR-378a-3p. Existing databases were used to computationally predict and analyze mir-378a-3p potential targets. We show that short-term exposure to OB or OBD patients’ plasma is sufficient to affect C2C12 properties. In fact, the expression of genes that regulate skeletal muscle differentiation and growth was downregulated in both OB- and OBD-treated cells, maximal mitochondrial respiration rate was downregulated in the OBD group, while in the OB group, a metabolic switch to glycolysis was detected. These alterations correlated with a decrease in ATGL and Pgc1b expression in the OB group and with an increase of miR-378a-3p levels in the OBD group.