Dysregulation of adipose tissue functions makes a significant contribution to the pathogenesis of metabolic syndrome, one of the most common diseases in recent years. Adipose tissue is an organ that secretes at least several dozen signaling molecules, adipokines. One of the most studied and at the same time mysterious adipokines is adiponectin. The latter is due to the lack of clear ideas about the biological role of this adipokine, the presence of its several molecular forms with different activity and several types of receptors to this adipokine localized in almost all cells of the body. The purpose of this review is to summarize and analyze the available information about the molecular mechanisms of the effect of adiponectin on metabolism of carbohydrates, lipids and lipoproteins. The literature search was conducted by the keywords "adiponectin" and "metabolic syndrome" in the Pubmed and Elibrary.ru databases for the period from 1995 to 2021.

According to the results of the literature analysis, it is assumed that adiponectin is involved in energy metabolism as a «satiety» hormone that promotes the utilization and storage of energy-rich substrates, fatty acids and glucose, which prevents the development or mitigates the already developed insulin resistance. This reduces the amount of plasma triglycerides and increases the level of high-density lipoproteins in the plasma. Adiponectin affects metabolic processes by activating the AdipoR1-APPL1-LKB1-AMPK, AdipoR1-APPL1-p38, AdipoR2-PPARa cascades, and possibly by activating the ceramidase and phosphoinositide pathways and insulin signaling. In addition to the AdipoR1/2 receptors, the adhesion molecule T-cadherin may be involved in the transduction of the adiponectin signal in endothelial and muscle cells. The mechanisms of signal transduction from T-cadherin, as well as from AdipoR2, remain unclear. Studies on the mechanisms of the action of individual molecular forms of adiponectin are extremely rare. The analysis shows the complex nature of adiponectin signaling, many of the mechanisms of  which remain undiscovered, and it is possible that the near future will bring us significant progress in this area.

Melatonin is a special hormone that act as an internal synchronizer of circadian rhythms, the organism physiology and behavior to the environmental day and night and seasons of the year. The present urban society and the industrial production processes as organized should be considered, as both depend on the presence of indoor lights during the night and include the profuse use of electronic devices whose screens are rich in blue wavelength light. Light during the night delays the beginning of the secretory episode of melatonin and blunts its peak, causing chronic hypomelatoninemia. Hypomelatonemia, that causes deprivation of sleep and eating behavior disorders, along with low physical activity, can be the reason of the obesity, «non-infectious epidemic of the 21^st century». According to this, the use of melatonin drugs for obesity treatment can be effective. Further prospective, controlled, randomized trials in this area are required to confirm this hypothesis.

Large prospective studies involving several hundred thousands to several million people from the general population have shown that people with obesity have a higher overall mortality rate than people with a normal BMI. The use of BMI in predicting the prognosis of people with cardiovascular disease has led to the inverse relationship between BMI and risk of death. Obesity, determined by BMI, is very heterogeneous in determining prognosis in different groups of patients. The use of imaging techniques during the examination revealed that poor health effects are associated with the accumulation of visceral adipose tissue. New evidence also suggests that ectopic deposition of fat (in the liver, in the epicardium) may increase the risk of developing atherosclerosis and cardiovascular disease and type 2 diabetes. The number of studies examining the direct effect of visceral adipose tissue on mortality is very limited. Their results are extremely contradictory, based not on prospective observations, but on the construction of statistical models. Adipose tissue is currently considered as an endocrine and paracrine organ. Deposition of adipose tissue in the internal organs, in addition to metabolic disorders), probably leads to the formation of local adverse effects. The above data lead us to the conclusion that it is necessary to create a new classification that would improve the stratification of the risk of developing cardiovascular disease and death in people with obesity.

Obesity and functional bowel disease (FBD) are affecting a large number of people worldwide. They have psychosocial consequences and associated with considerable healthcare resource use. The purpose of this review was a comprehensive study of the relationship between obesity and FBD, as well as mechanisms to explain this relationship. An analysis of the literature provides strong evidence of a link between obesity and diarrhea, but there is currently insufficient data to speak confidently about the link between obesity and irritable bowel syndrome. Most studies suggest that adult obesity is not associated or negatively associated with constipation. The association of obesity with diarrhea is most convincingly explained through diet, eating behavior, changes in the metabolism of bile acids, accelerated colonic transit, altered intestinal microbiota and associated inflammation and increased intestinal permeability. Medicines taken by patients, as well as non-alcoholic fatty liver disease, can play their own role.

Planning and conducting studies, including longitudinal ones, based on valid diagnostic criteria and taking into account the widest possible range of confounders, will allow a deeper study of the problem of comorbidity of obesity and FBD. This will help optimize the treatment of these diseases.

Metabolic syndrome is a symptom complex that is based on visceral obesity and insulin resistance. Its prevalence is quite high, which is a big problem, since this condition increases the risk of developing cardiovascular diseases and mortality from them. Metabolic syndrome includes, in addition to abdominal obesity, arterial hypertension, disorders of carbohydrate, lipid and purine metabolism. Visceral adipose tissue plays a key role in the formation of insulin resistance and other components of the metabolic syndrome. This is due to the fact that abdominal fat, in contrast to subcutaneous fat, synthesizes pro-inflammatory cytokines, as well as adipokines — adipose tissue hormones that are involved in the formation of insulin resistance, affect carbohydrate and fat metabolism and the cardiovascular system. These include leptin, adiponectin, resistin, apelin and others. Some adipokines have an adverse effect on metabolism and increase cardiovascular risks, while others, on the contrary, have a positive effect. Taking into account their role in the development of the components of the metabolic syndrome, the possibilities of a therapeutic effect on the hormones of adipose tissue to improve metabolic processes and prevent complications associated with it are discussed.

Acromegaly is a severe disabling neuroendocrine disease caused by hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). The problem of resistance to drug therapy in patients with acromegaly is quite common in clinical practice and requires a personalized approach, considering various predictors of sensitivity to the choice of the treatment method. To date, first-generation somatostatin analogues are first-line drugs in the medical treatment of acromegaly, but up to 50% of patients do not achieve biochemical remission of the disease. The prognosis of sensitivity to somatostatin analogues is of great importance and the selection of patients in whom this therapy will be not successful provides invaluable assistance in choosing the optimal treatment approach. This review summarizes potential predictors of sensitivity and resistance to existing drug treatment of acromegaly, discusses possible ways to overcome the resulting resistance to therapy, suggests options for a personalized approach to choosing a treatment strategy in the absence of disease control against the background of monotherapy with somatostatin analogues, including «off-label» combinations. Timely addition of growth hormone receptor antagonist (pegvisomant) avoids repeated neurosurgical intervention, radiation therapy or prescribing excessively high doses of somatostatin analogues. Optimal use of mono- or combination therapy contributes to the achievement of biochemical remission in most resistant patients.

Obesity is an important health problem in many countries. Obesity among the child population is growing steadily, including the Russian Federation. Development of this disease often occurs in childhood and sometimes the origin of obesity goes back to prenatal period. There are a number of endogenous and exogenous factors than play an important role in development of obesity. These are heredity, socioeconomic status of the family, factors which are revealed during pregnancy and child delivery — weight gain, administration of antibacterial drugs and hyperglycemia in mother during her pregnancy, mode of delivery, feeding type and time of complementary food introduction, excessive consumption of calories with food, improper daily routine and lack of sleep, skipping meals, use of gadgets and associated physical inactivity and excessive food intake, marketing of high-calorie foods and others. Prevailing risk factors can be identified for each age period. Study and early identification of risk factors taking into account age of a child is necessary to take timely prevention measures and inform parents and their children about possible reasons and consequences of obesity.

The influence of obesity on human health, as a multifactorial and multigenic disorder, is a rather complex, interdisciplinary and at the same time extremely urgent problem of modern society. Vitamin D deficiency is one of the consequences of obesity that negatively affects a person’s life expectancy. Vitamin D deficiency is rightfully considered a silent, non-infectious metabolic pandemic of the 21st century. Its significant role in the functioning of the human body is deep and multifaceted, since vitamin D is an integral regulator of the transcriptional activity of genes that control 3–5% of the human genome. There are ongoing discussions among experts in the medical community about the negative impact of obesity on 25 (OH) D levels, and the opposite hypothesis is also being discussed, where vitamin D deficiency is considered an independent risk factor for obesity. Both external causes of the formation of vitamin D deficiency against the background of excessive deposition of adipose tissue and internal metabolic processes underlying the pathogenetic association are analyzed two pathological conditions.

Hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia and hyperphosphatemia, due to absent or inappropriately low serum parathyroid hormone (PTH) levels. The chronic postoperative hypoparathyroidism accounts approximately 75% of patients; the genetic, autoimmune or idiopathic forms are significantly less common. Today, chronic hypoparathyroidism remains the last major endocrine deficiency, for which hormonal replacement therapy has not found widespread use. Achieving the target levels of phosphorus-calcium metabolism is an important factor of the disease control, required for the prevention of short- and long-term complications. The standard therapy with active metabolites/analogues of vitamin D (­alfacalcidol, calcitriol) and calcium supplements does not always allow to achieve the target treatment goals. Despite high doses of calcium and active vitamin D, some patients suffer from unstable calcium levels and associated symptoms.

The measurement of serum calcium and phosphorus in the early morning hours remains the main laboratory tests for such patients, but in sometimes this diagnostic approach does not really reflect the true picture.

The presented clinical cases describe the changes of both hyper- and hypocalcemia within one day in patients with chronic postsurgical hypoparathyroidism managed by standard therapy.

Background: Hyperprolactinemia is one of the most common hypothalamic-pituitary-endocrine disorders in women of reproductive age, with the highest frequency at the age of 25–44 years. In addition to influencing the reproductive system, it is important to study the effects of prolactin (PRL) on various metabolic links. Available data indicate that the effect of PRL on metabolism depends on its level. In this regard, the study of the relationship of different levels of PRL with anthropometric parameters, indicators of lipid and carbohydrate metabolism in young women is relevant.

Aim: To study the frequency of metabolic syndrome (MS) and its individual components in women aged 25–45 years with different levels of prolactin.

Materials and methods: Work design — cross-sectional research. A randompopulationsample of women 25–45 agedwas examined. Pregnant and breastfeeding women with macroprolactinoma, and taking antipsychotics were excluded. Information was collected using a structured ­questionnaire, including, but not limited to, the presence of pregnancies, childbirth, menstrual irregularities, and a clinical examination, anthropometric measurements, biochemical and hormonal blood analyzes were performed. Statistical data processing was carried out.

Results: According to the inclusion and exclusion criteria, this analysis presents data from 401 women, the average age of the examibed was 36.14±6.19 years. There was no difference in the levels of thyroid-stimulating hormone and prolactin (PRL) in the age groups of 25–34 and 35–45 years. According to the survey, the incidence of thyroid diseases in the studied groups is comparable. Every fifth woman indicated menstrual irregularities. Among women 25–45 years old, women with low-normal PRL values (Me = 4.49 [3.52; 5.41] ng/ml) have more unfavorable metabolic indicators. Metabolic syndrome (MS) was detected in 28%,with a predominant increase in the frequency of abdominal obesity — 55%, hypercholesterolemic LDL — 63%. Women with high PRL (Me = 41.35 [34.78; 45.88] ng / ml) also have an unfavorable metabolic profile: MS was detected in 47%, abdominal obesity — 56%, hypertension — 39%.

Conclusions: In women 25–45 years old, low and high PRL values are more often associated with metabolic ill health. PRL values are from 7.8 to 28 ng / ml, i.e. conditionally defined as normal, highly normal and at the level of moderate hyperprolactinemia contribute to the maintenance of a favorable metabolic profile. When deciding on the treatment of women with non-tumor etiology hyperprolactinemia, it is important to assess the metabolic status, expanding their understanding of PRL as a hormone associated only with lactation and with the pituitary-gonad axis.

Background: The problem of high blood pressure in the framework of metabolic syndrome (MS) is one of the most important for modern medicine in connection with the predicted increase in the incidence in the future and an increase in the mortality rate from cardiovascular disease.

Aims: the aim of the study is to examine the frequency of arterial hypertension (AH) as part of the MS among the members of the indigenous population of the Mountain Shoria and to state the degree of the interconnection between the expression level of the candidate genes ACE, AGT, AGTR1, MTHFR and NOS3 and certain health problem.

Materials and methods: The sample included 901 members of the indigenous population living in the settlements of the Mountain Shoria region. All experimental subjects had their blood pressure measured, anthropometry (measurements of height, body weight, waist circumference) taken according to standard procedures, fasting blood taken to determine the lipid spectrum and glucose level, morning urine dose taken and albumin level detected. All the patients with hypertension underwent duplex scanning of the brachycephalic arteries and examination of the structural and functional state of the myocardium was performed using echocardiography. Gene polymorphisms ACE (I/D, rs4340), AGT (c.803T>C, rs699), AGTR1 (A1166C, rs5186), MTHFR (c.677C>T, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) were tested using polymerase chain reaction.

Results: Among the indigenous population of the Mountain Shoria, the frequency of hypertension combined with abdominal obesity and any other additional component of MS was 28.2%. In the group of the patients with, organ changes in the form of left ventricular myocardial hypertrophy and an increase in the thickness of the intima-media complex were more common than in the group of patients with AH alone: 58.0% versus 45.1%, p = 0.029 and 81.9% versus 67 , 0%, p = 0.007, respectively. The high risk of hypertension within the framework of MS was determined by the D allel of the ACE gene [OR = 2.45; 95% CI (1.05-5.72)].

Conclusions: The high frequency of the spread of high blood pressure within MS confirms that hypertension is less frequently manifested as an isolated disease, more often combined with other components of MS — abdominal obesity or disorders of carbohydrate and lipid metabolism. Stated genetic predisposition to hypertension within the MS in a specific small cohort of the Shors will undoubtedly help in the development and implementation of the health programs.

Background: The prevalence of obesity and metabolic abnormalities is increased patients with mental disorders receiving psychopharmacotherapy, which significantly impairs their treatment adherence.

Aims: To evaluate the efficacy and safety of metformin in prevention and treatment obesity and overweight in patients with mental disorders receiving antipsychotics.

Materials and methods: This was an open-label, prospective, randomized, placebo-controlled study of female patients with mental disorders (age, 18 to 50). The patients were randomized into two groups in a 2:1 ratio: the treatment group received metformin and the control group received placebo. Metformin was administered at a starting dose of 500 mg daily, with subsequent up-titration every 2 weeks when necessary, up to 2000 mg daily. The treatment duration was 6 months.

Results: Baseline BMI in the treatment group (N=62) was 27,3 [24,0; 30,4] kg/m²; it decreased to 26,0 [22,5; 30,5] kg/m², p < 0.0001, Wilсoxon test) after 6 months of treatment. The patients receiving metformin decreased their body weight by 3 [-6; 0] kg, or  -4,0 [-8; 0] %. In the placebo group (N=30), the baseline BMI was 27,5 [24,0; 32,0] kg/m² and increased to 28,2 [25,8; 34,0] kg/m² at 6 month (p=0.001, Wilсoxon test), or 3 [1; 6] kg. After 6 months of treatment, the difference in BMI between the metformin and placebo groups was significant (26,0 и 28,2 kg/m², respectively, р=0,027, Mann-Withney test). Six (6) of 62 patients treated with metformin had side effects and were switched to an equivalent dose of prolonged release metformin, with reduction of side effects in 5 of them.

Conclusions: The use of metformin in patients with mental disorders receiving antipsychotics allows for reduction or stabilization of body weight in 80% of cases, with ≥5% decrease of body weight in 44% of patients. It is recommended to start metformin at a dose of 500 mg daily with subsequent up-titration of up to 2000 mg if necessary.

Background: Osteoarthritis (OA) is a significant social problem as it is the most common disease of the joints. OA is a multifactorial disease in which great attention is paid to hereditary factors. Recently, a number of studies have demonstrated the contribution of a number of genes to the subjective assessment of pain in OA, which is the main symptom of this disease. The association of P2X7, TRPV1 and TACR1 genes and some others with pain sensitivity has been shown. One of the risk factors of pain among many others, is the increased weight. Abdominal adipose tissue is a source of release of pro-inflammatory adipokines that cause systemic inflammation associated with damage to many tissues, including subchondral bone, synovial membrane. Leptin is an endogenous hormone from the adipokine family encoded by the obesity gene leptin (LEP) and which is synthesized primarily in adipocytes.

Aims: To investigate the possible association of rs2167270 (A19G) polymorphism of the LEP gene with pain intensity in ­patients with knee OA.

Materials and methods: The study was conducted among women diagnosed with OA. Using the VAS scale (Visual analog scale), patients with mild knee pain — group 1 (VAS ≤ 40 mm) and patients with moderate or severe pain — group 2 (VAS>40 mm) were selected for pain assessment. Genetic variants of A19G leptin gene polymorphism were studied by polymerase chain reaction followed by restriction fragment length analysis (PCR-RFLP) method.

Results: In the group of patients with moderate or severe pain intensity (group 2, n=61), a statistically significant association was shown with a higher body mass index (p=0.006) and an increased frequency of carriers of the 19GG genotype (p=0,051) compared to group 1 (n=36). Carriers of the 19GG genotype statistically significantly had a higher rate of knee pain and an early age of OA debut compared to carriers of the 19AA genotype (p=0,035 and p=0,015, respectively).

Conclusions: The findings open up new possibilities for predicting pain symptoms in patients with knee OA by genetic testing of A19G polymorphic variants of the leptin gene.

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.