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.

(1) Background: Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, and its activation has become a new object as both a determinant of metabolic health and a target for therapy. This study aimed to identify the relationships between the presence of BAT, parameters that characterize metabolic health (glucose, lipids, blood pressure (BP)), and the dynamics of body mass index (BMI) during weight-reducing therapy. (2) Methods: The study included 72 patients with obesity. We investigated metabolic parameters, anthropometric parameters, and BP. Dual-energy X-ray absorptiometry (DXA) and positron emission tomography and computed tomography (PET/CT) imaging with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) were performed. (3) Results: Before weight-reducing therapy, BAT was revealed only in 19% patients with obesity. The presence of BAT was associated with a lower risk of metabolic deviations that characterize metabolic syndrome: shorter waist circumference (WC) (p = 0.02) and lower levels of glucose (p = 0.03) and triglycerides (p = 0.03). Thereafter, patients were divided into four groups according to the type of therapy (only lifestyle modification or with Liraglutide or Reduxin or Reduxin Forte). We did not find a relationship between the presence of BAT and response to therapy: percent weight reduction was 10.4% in patients with BAT and 8.5% in patients without BAT (p = 0.78) during six months of therapy. But we noted a significant positive correlation between the volume of BAT and the effectiveness of weight loss at 3 months (r = 0.52, p = 0.016). The dynamic analysis of BAT after 6 months of therapy showed a significant increase in the volume of cold-induced metabolically active BAT, as determined by PET/CT with ¹⁸F-FDG in the Liraglutide group (p = 0.04) and an increase in the activity of BAT standardized uptake value (SUV mean and SUV max) in the Reduxin (p = 0.02; p = 0.01, respectively) and Liraglutide groups (p = 0.02 in both settings). (4) Conclusions: The presence of brown adipose tissue is associated with a lower risk of metabolic abnormalities. In general, our study demonstrated that well-established drugs in the treatment of obesity (Liraglutide and Reduxin) have one more mechanism for implementing their effects. These drugs have the ability to increase the activity of BAT. A significant positive relationship between the total volume of BAT and the percentage of weight loss may further determine the priority mechanism of the weight-reducing effect of these medicaments.

Background: Obesity is a global noncommunicable pandemic. The low effectiveness of treating obesity is associated with the difficulty of maintaining weight loss due to the reaction of the appetite regulation system. Drugs with central mechanisms of action can help overcome this problem.Aim: The aim of our study was to compare the effects of liraglutide and sibutramine (Reduxin) on the dynamics of weight and cardiometabolic parameters in obese patients without cardiovascular diseases.Materials and methods: We estimated the dynamics of the main metabolic parameters (BMI, glucose, lipid metabolism, blood pressure), the level of hormones involved in the regulation of fat metabolism (leptin, adiponectin, insulin), the ­HOMA-IR index, markers of oxidative stress and inflammation during therapy with liraglutide in comparison with reduxin for 6 months in obese patients.Results: 64 obese patients were included in the study: 25 patients — in the “Liraglutide” group, 39 patients — in the “Sibutramine” group in accordance with the declared inclusion / exclusion criteria. The included patients were young, average body mass index (BMI) (37.92 ± 5.45 kg / m²), average glycemic level was 5.47 ± 0.81 mmol /l, HOMA-IR was 6.01 ± 4.25, blood pressure was at inclusion was within the normal range, but 21.8% of patients received antihypertensive therapy.Both treatment options provided a comparable decrease in body weight (-10.28% vs -9.47%, p = 0.13)., Leptin level (-32.12% vs -41.77%, p = 0.77) and myeloperoxidase (-33.33% vs -19.91%, p = 0.2). The blood pressure level did not change significantly on liraglutide, while on reduxin the level of diastolic blood pressure (dBP) increased significantly (6.87%, p = 0.006). There was a more pronounced decrease in insulin levels compared to the baseline level (-46%, p = 0.005), as well as a decrease in the HOMA-IR index (-50.08, p = 0.005) on liraglutide therapy.An increase in adiponectin levels (+ 45.36% vs 14.01%, p = 0.0045) and a decrease in low density lipoprotein(LDL) cholesterol were significantly more pronounced on reduxin therapy (-15.03% vs -9.4%, p = 0.006).36% of the participants completed their participation in the study ahead of schedule due to the lack of effect in the form of weight loss in the «Liraglutide» group. Side effects in the “Liraglutide” group were observed in 16% of patients. 48% of patients took part in the study within 6 months. In the «Sibutramine» group 33.4% of patients completed the study ahead of schedule for reasons unrelated to the drug intake, the side effects were observed in 20.5% of patients. 46.1% of participants in the «Sibutramine» group received therapy for 6 months.Conclusions: This study confirms the previous findings that both liraglutide and reduxin therapy provide effective weight loss. We found a positive trend in markers of inflammation, atherogenesis and oxidative stress, and leptin levels. Liraglutide therapy was accompanied by a more pronounced effect on the state of carbohydrate metabolism, and reduxin therapy provided a more pronounced dynamics of lipid disorders and adiponexin. Both groups were characterized by a rather low adherence to therapy, but the incidence of side effects requiring stopping therapy was higher in the Sibutramine group.

Metabolically healthy (MHO) and unhealthy obesity (MUO) exhibit distinct molecular genetic mechanisms underlying metabolic disorders. Studying gene and microRNA expression in subcutaneous adipose tissue (SAT) may reveal key pathogenetic differences between these phenotypes. We compared the expression of genes (ADIPOQ, HIF1A, CCL2) and microRNAs (miR-142-3p, miR-155, miR-378) in SAT between MHO and MUO patients and assessed their association with metabolic parameters. The study included 39 obese patients (19 MHO, 20 MUO) and 10 healthy controls. SAT biopsies were analyzed using real-time PCR. Correlations with clinical and metabolic markers were evaluated. Obese patients showed decreased ADIPOQ (p = 0.039) and miR-142 (p = 0.008) expression and increased CCL2 (p = 0.004), miR-155 (p = 0.017), and miR-378 (p = 0.04) expression compared to the controls. MUO patients exhibited higher HIF1A expression (p = 0.03) and strong correlations between CCL2 and dyslipidemia (total cholesterol, triglycerides)/dysglycemia (fasting glucose) (r = 0.45, p = 0.03; r = 0.52, p = 0.01; r = 0.63, p = 0.001, respectively). miR-142 negatively correlated with fibrosis markers, while miR-378 was linked to insulin resistance. The differential gene and microRNA expression highlights the role of inflammation, hypoxia, and fibrosis in MUO pathogenesis. miR-142-3p, miR-155, and miR-378 may serve as potential biomarkers for metabolic risk stratification and therapeutic targets.

Background/Objective: This study is a cross-sectional investigation of long-term immune responses measured at different time intervals after COVID-19 infections, vaccinations, or combined exposure. The focus is on immune reactivity against recombinant spike (S) and nucleocapsid (N) protein antigens. Materials and Methods: Serum antibody levels were assessed up to four to four and a half years after infection or immunization, including virus-specific immunoglobulin G (IgG), IgA and IgM antibodies, as well as neutralizing antibodies against the S-protein. Cellular immunity was assessed by analyzing peripheral blood mononuclear cells (PBMC; n = 43 in first cohort, n = 32 in second cohort), including T-helper memory and cytotoxic subsets, and cytokine production after in vitro stimulation with recombinant SARS-CoV-2 proteins. A multiplex cytokine assay was used to analyze effector and regulatory immune responses. Results: Virus-specific IgG antibodies persisted for years after exposure to SARS-CoV-2, with IgG against the receptor-binding domain (RBD) correlating most strongly with neutralizing activity. Vaccinated individuals demonstrated higher IgA responses, whereas antibodies to the N-protein were associated with previous infection. No IgM antibodies were detected in any subjects, suggesting an immune response based on memory rather than ongoing infection. PBMCs from individuals with a history of both COVID-19 exposure and vaccination exhibited enhanced responsiveness, characterized by increased frequencies of memory T cells compared to vaccination alone. Stimulating with the S-protein induces higher cytokine production, including IFN-gamma, TNF-alfa, and IL-12(p70), compared with stimulation by the N-protein. Cytokines such as IL-10 and TGF-beta are also elevated, suggesting immune regulation rather than persistent inflammation. Conclusions: SARS-CoV-2 infection and vaccination are associated with persistent humoral and cellular immune responses detectable several years after exposure. Individuals with hybrid immunity exhibit broader and functionally enhanced immune reactivity, indicating more robust long-term immune memory. Future studies should focus on the long-term consequences of hybrid immunity and optimize other vaccine strategies, including recombinant antigen vaccines.