Adipose Tissue-derived Hormone Research Articles

Adiponectin Stimulates Apolipoprotein A-1 Gene Expression in HepG2 Cells via AMPK, PPARα, and LXRs Signaling Mechanisms.

Adiponectin is an adipose tissue hormone, participating in energy metabolism and involved in atherogenesis. Previously, it was found that adiponectin increases expression of the APOA1 (apolipoprotein A-1) gene in hepatocytes, but the mechanisms of this effect remained unexplored. Our aim was to investigate the role of adiponectin receptors AdipoR1/R2, AMP-activated protein kinase (AMPK), nuclear peroxisome proliferator-activated receptor alpha (PPARα) and liver X receptors (LXRs) in mediating the action of adiponectin on hepatic APOA1 expression in human hepatoma HepG2 cells. The level of APOA1 expression was determined by RT-qPCR and ELISA. We showed that the siRNA-mediated knockdown of genes coding for AdipoR1, AdipoR2, AMPK, PPARα, and LXRα and β prevented adiponectin-induced APOA1 expression in HepG2 cells and demonstrated that interaction of PPARα and LXRs with the APOA1 gene hepatic enhancer is important for the adiponectin-dependent APOA1 transcription. The results of this study point out to the involvement of both types of adiponectin receptors, AMPK, PPARα, and LXRs in the adiponectin-dependent upregulation of the APOA1 expression.

Therapeutic Target Analysis and Molecular Mechanism of Melatonin - Treated Leptin Resistance Induced Obesity: A Systematic Study of Network Pharmacology.

BackgroundObesity is a medical problem with an increased risk for other metabolic disorders like diabetes, heart problem, arthritis, etc. Leptin is an adipose tissue-derived hormone responsible for food intake, energy expenditure, etc., and leptin resistance is one of the significant causes of obesity. Excess leptin secretion by poor diet habits and impaired hypothalamic leptin signaling leads to LR. Melatonin a sleep hormone; also possess antioxidant and anti-inflammatory properties. The melatonin can attenuate the complications of obesity by regulating its targets towards LR induced obesity.AimThe aim of this study includes molecular pathway and network analysis by using a systems pharmacology approach to identify a potential therapeutic mechanism of melatonin on leptin resistance-induced obesity.MethodsThe bioinformatic methods are used to find therapeutic targets of melatonin in the treatment of leptin resistance-induced obesity. It includes target gene identification using public databases, Gene ontology, and KEGG pathway enrichment by ‘ClusterProfiler’ using the R language, network analysis by Cytoscape, and molecular Docking by Autodock.ResultsWe obtained the common top 33 potential therapeutic targets of melatonin and LR-induced obesity from the total melatonin targets 254 and common LR obesity targets 212 using the data screening method. They are involved in biological processes related to sleep and obesity, including the cellular response to external stimulus, chemical stress, and autophagy. From a total of 180 enriched pathways, we took the top ten pathways for further analysis, including lipid and atherosclerosis, endocrine, and AGE-RAGE signaling pathway in diabetic complications. The top 10 pathways interacted with the common 33 genes and created two functional modules. Using Cytoscape network analysis, the top ten hub genes (TP53, AKT1, MAPK3, PTGS2, TNF, IL6, MAPK1, ERBB2, IL1B, MTOR) were identified by the MCC algorithm of the CytoHubba plugin. From a wide range of pathway classes, melatonin can reduce LR-induced obesity risks by regulating the major six classes. It includes signal transduction, endocrine system, endocrine and metabolic disease, environmental adaptation, drug resistance antineoplastic, and cardiovascular disease.ConclusionThe pharmacological mechanism of action in this study shows the ten therapeutic targets of melatonin in LR-induced obesity.

Leptin and adiponectin regulate the activity of nuclei involved in sleep-wake cycle in male rats.

Epidemiological and experimental evidence recognize a relationship between sleep-wake cycles and adiposity levels, but the mechanisms that link both are not entirely understood. Adipose tissue secretes adiponectin and leptin hormones, mainly involved as indicators of adiposity levels and recently associated to sleep. To understand how two of the main adipose tissue hormones could influence sleep-wake regulation, we evaluated in male rats, the effect of direct administration of adiponectin or leptin in the ventrolateral preoptic nuclei (VLPO), a major area for sleep promotion. The presence of adiponectin (AdipoR1 and AdipoR2) and leptin receptors in VLPO were confirmed by immunohistochemistry. Adiponectin administration increased wakefulness during the rest phase, reduced delta power, and activated wake-promoting neurons, such as the locus coeruleus (LC), tuberomammillary nucleus (TMN) and hypocretin/orexin neurons (OX) within the lateral hypothalamus (LH) and perifornical area (PeF). Conversely, leptin promoted REM and NREM sleep, including increase of delta power during NREM sleep, and induced c-Fos expression in VLPO and melanin concentrating hormone expressing neurons (MCH). In addition, a reduction in wake-promoting neurons activity was found in the TMN, lateral hypothalamus (LH) and perifornical area (PeF), including in the OX neurons. Moreover, leptin administration reduced tyrosine hydroxylase (TH) immunoreactivity in the LC. Our data suggest that adiponectin and leptin act as hormonal mediators between the status of body energy and the regulation of the sleep-wake cycle.

Sex difference in human olfactory sensitivity is associated with plasma adiponectin

Energy deprivation as well as hormones that regulate appetite and eating can influence olfactory function. This study investigated olfactory sensitivity for a food-related and a non-food odour prior to and after a meal, and its relationship to the energy-regulating hormones ghrelin and adiponectin.The olfactory sensitivity for orange and rose (PEA) odour in healthy, normal-weight volunteers (19 women, 45 men, 1 undisclosed individual) was not affected by the consumption of a meal. Olfactory sensitivity was not associated with concentrations of circulating ghrelin. However, olfactory sensitivity was higher for women than for men, indicating better olfactory performance. This difference between women and men was related to concentrations of plasma adiponectin, an adipose-specific hormone.Adiponectin may thus explain why sex differences in olfactory sensitivity emerge, and may also account for some of the inconsistencies in previous findings on sex differences. Our findings add to the limited literature on the impact of stomach and adipose tissue-derived hormones on olfactory sensitivity. Further studies are needed to establish a causal link between circulating adiponectin and a sex difference in olfactory sensitivity.

New Aspects of Corpus Luteum Regulation in Physiological and Pathological Conditions: Involvement of Adipokines and Neuropeptides.

The corpus luteum is a small gland of great importance because its proper functioning determines not only the appropriate course of the estrous/menstrual cycle and embryo implantation, but also the subsequent maintenance of pregnancy. Among the well-known regulators of luteal tissue functions, increasing attention is focused on the role of neuropeptides and adipose tissue hormones—adipokines. Growing evidence points to the expression of these factors in the corpus luteum of women and different animal species, and their involvement in corpus luteum formation, endocrine function, angiogenesis, cells proliferation, apoptosis, and finally, regression. In the present review, we summarize the current knowledge about the expression and role of adipokines, such as adiponectin, leptin, apelin, vaspin, visfatin, chemerin, and neuropeptides like ghrelin, orexins, kisspeptin, and phoenixin in the physiological regulation of the corpus luteum function, as well as their potential involvement in pathologies affecting the luteal cells that disrupt the estrous cycle.

The importance of laboratory parameters of the lipid transport system and adipose tissue hormones in assessing the course of chronic.

The main manifestations of metabolic syndrome (MS) are disorders of carbohydrate and lipid metabolism and their hormonal regulation. The combined nature of metabolic disorders can significantly affect the course and prognosis of CHF in elderly people with metabolic syndrome. To determine the features of the combined effect of metabolic laboratory parameters and biological active factors of adipose tissue in patients with CHF and metabolic syndrome on the course of the disease. A comparison was made between a group of patients with CHF complicated by MS(n=37) and a group of patients with CHF without MS (n=37). The parameters of lipid metabolism (cholesterol CH and lipoproteins LP), the lipid transport system (ApoA1 and ApoB), leptin, adiponectin and resistin and their mutual relations were studied. The ratio of ApoB/ApoAI levels was indicative, which was 0.80±0.32 in patients with CHF without MS, and 1.12±0.46 in patients with CHF with MS (p <0.05). A significant correlation was found between the ratio of ApoB/ApoA1 levels and abdominal obesity (r=0.42, p<0.05), functional class of CHF (r=0.463, p<0.05), LDL-C level (r=0.518, p<0.05), and triglycerides (r=0.476, p<0.05). Also, significant results were obtained for the leptin/adiponectin ratio. For this ratio, 4 ranks were derived depending on the value of the leptin (ng/ml)/adiponectin (mcg/ml) ratio: less than 1 - rank 0 was assigned, with values of the ratio in the range 1 - 3 - rank 1, in the range 3.1 - 6 - rank 2, and above the value 6 - rank 3. Of the 22 patients who had improved CHF at the end of hospitalization, all at the beginning of hospitalization had a rank 0 or 1 ApoB/ApoA1 ratio. Thus, ranking the values of the ratio of ApoB/ApoA1 levels, and especially leptin/adiponectin, can suggest the probability of successful treatment of CHF or the probability of deterioration of the patient's condition, up to a fatal outcome.

The nonshivering thermogenesis of brown adipose tissue and fat mobilization of striped hamsters exposed to cycles of cold and warm temperatures

The adaptive adjustments in the capacity for metabolic thermogenesis are critical for the survival in many small mammals that are acclimated to cold winter conditions. In this study the striped hamsters (Cricetulus barabensis) were subjected to repeated cycles of cold (5°C) and warm (23°C) temperatures. Resting metabolic rate (RMR), nonshivering thermogenesis (NST) and energy intake, as well as the expression of uncoupling protein 1 (UCP1) of brown adipose tissue (BAT) and serum thyroid hormone levels were measured. Both RMR and NST were significantly increased in striped hamsters subjected to repeated cycles of short-term cold (5°C, 72 h) – warm (23°C, 4 days) temperatures compared to that of the hamsters consistently kept at 23°C. In these cycled hamsters, BAT UCP1 expression was significantly upregulated, whereas serum T3 and T4 concentration did not change significantly. Moreover, gross energy intake was considerably increased during both cold exposure and warm phases, whereas fat deposition was significantly decreased in these cycled hamsters compared to those consistently kept at 23°C. This indicates that small mammals may both increase energy intake and mobilize fat depots to cope with frequent cold exposure. Thyroid hormone may be not involved in the BAT UCP1-mediated thermogenesis and fat mobilization.

Correlation of serum apelin level with carotid intima–media thickness and insulin resistance in a sample of Egyptian patients with type 2 diabetes mellitus

Background:Type 2 diabetes mellitus (T2DM) is a growing health problem in Egypt, with a significant impact on morbidity and mortality. Measurement of the carotid Intima-media thickness (CIMT) allows early detection of atherosclerotic blood vessel diseases. Apelin is an adipose tissue-derived hormone that may be associated with insulin resistance (IR). This study aimed to assess the level of serum apelin in patients with T2DM and its relation to IR and CIMT.Materials and Methods:A case-control study was conducted on 60 patients with T2DM and 30 healthy controls. T2DM was diagnosed based on American Diabetes Association criteria. The study was carried out at Al-Zahraa University Hospital, Cairo, Egypt, through the period from June to December 2019. The laboratory investigations included serum apelin and blood glucose hemostasis markers. CIMT was assessed using B-mode ultrasonography.Results:Patients’ group had a statistically significant higher apelin level than healthy controls (407.96 ± 291.07 versus 83.32 ± 10.55 ng/dL, P < 0.001). The correlation analysis showed that the serum apelin level correlated positively with glycemic indices, body weight, and waist circumference (P < 0.05). At cutoff value of >96 ng/dL, the serum apelin exhibited a sensitivity of 98.3% and specificity of 96.7%, positive predictive value of 98.1%, and negative predictive value of 96.5%, with a diagnostic accuracy of 95.1%. Serum apelin correlated positively with CIMT (r = 0.296, P = 0.022). Logistic regression analysis showed that systolic and diastolic blood pressures, Homeostasis Model Assessment of IR, and CIMT were independent predictors of serum apelin.Conclusion:Serum apelin may be correlated with the degree of carotid atherosclerosis and hence can be used as a prognostic biomarker.

Патогенетические аспекты коморбидного течения неалкогольной жировой болезни печени и желчнокаменной болезни: обзор и собственные данные

This paper reviews the pathogenic mechanisms of the development and progression of comorbid cholelithiasis (CL) and non-alcoholic fatty liver disease (NAFLD). The authors discuss gender and anatomic physiological patterns, and the effects of insulin resistance, obesity, adipose tissue hormones, and cholecystectomy on clinical morphological abnormalities in coexisting CL and NAFLD. In addition to lipid metabolism abnormalities, comorbid CL and NAFLD are characterized by deviations in the amount and proportions of fatty acids and hormonal imbalance (i.e., hyperleptinemia, leptin resistance, and insulin resistance). Cholecystectomy is an unfavorable factor for the progressive course of NAFLD and development of liver fibrosis. As a result, individualized management strategies are required in these cases. The authors present their own study that enrolled 183 patients with NAFLD. Their data demonstrate that coexisting NAFLD and CL have certain clinical laboratory signatures, while the postoperative period after cholecystectomy in patients with NAFLD is characterized by greater cardiovascular risk and liver fibrosis progression. The authors discuss the use of a combined preparation of ursodeoxycholic acid and sodium glycyrrhizinate in these patients. Two-component hepatoprotective treatment with this agent has pathogenically-target effect in comorbid NAFLD and CL. KEYWORDS: non-alcoholic fatty liver disease, cholelithiasis, comorbidity, liver fibrosis, cholecystectomy. FOR CITATION: Krolevets T.S., Livzan M.A., Syrovenko M.I., Cherkashchenko N.A. Pathogenic aspects of the comorbid course of non- alcoholic fatty liver disease and cholelithiasis: a review and the authors’ results. Russian Medical Inquiry. 2022;6(5):278–285 (in Russ.). DOI: 10.32364/2587-6821-2022-6-5-278-285.

Histone deacetylase 6 inhibition restores leptin sensitivity and reduces obesity.

The adipose tissue-derived hormone leptin can drive decreases in food intake while increasing energy expenditure. In diet-induced obesity, circulating leptin levels rise proportionally to adiposity. Despite this hyperleptinemia, rodents and humans with obesity maintain increased adiposity and are resistant to leptin’s actions. Here we show that inhibitors of the cytosolic enzyme histone deacetylase 6 (HDAC6) act as potent leptin sensitizers and anti-obesity agents in diet-induced obese mice. Specifically, HDAC6 inhibitors, such as tubastatin A, reduce food intake, fat mass, hepatic steatosis and improve systemic glucose homeostasis in an HDAC6-dependent manner. Mechanistically, peripheral, but not central, inhibition of HDAC6 confers central leptin sensitivity. Additionally, the anti-obesity effect of tubastatin A is attenuated in animals with a defective central leptin-melanocortin circuitry, including db/db and MC4R-KO mice. Our results suggest the existence of an HDAC6-regulated adipokine that serves as a leptin-sensitizing agent, and reveals HDAC6 as a potential target for the treatment of obesity.

COVID-19 Outcome Relates With Circulating BDNF, According to Patient Adiposity and Age.

Background and Aims: We evaluated adipose tissue-derived hormones, body composition, serum metabolic profile, levels of brain-derived neurotrophic factor (BDNF), and the association of these parameters with the clinical outcome in patients with COVID-19. We sought to examine whether obesity, sex, and age influence the adipose tissue endocrine response to the disease.Methods: This prospective study investigated 145 hospitalized patients with COVID-19. Patients were categorized based on their body mass index (BMI), sex and age, and were also classified regarding their outcome after hospitalization as: (a) Non-ICU: patients hospitalized who did not receive intensive care; (b) ICU-survivor: patients admitted to the intensive care unit and discharged; (c) ICU-death: patients who died. Blood samples were collected by the hospital staff between the first and third day of hospitalization. Serum leptin, adiponectin and BDNF concentrations, triglycerides, total cholesterol and cholesterol fractions were performed following the manufacturer's guidelines.Results: We demonstrate that BDNF levels predict intensive care (IC) need (p < 0.01). This association was found to be stronger in patients >60y (p = 0.026). Neither leptin nor adiponectin concentration was associated with IC requirement or with patient's outcome, while the BDNF/adiponectin ratio was closely associated with worsened outcomes (p < 0.01). BDNF concentration was similar between sexes, however tended to be lower in male patients (p = 0.023). In older patients, BDNF concentration was lower than that of younger patients (p = 0.020). These age and sex-specific differences should be considered when employing these potential markers for prognosis assessment. While appetite and body composition regulating hormones secreted by the white adipose tissue are not reliable predictors of disease severity, the ratio BDNF/adiponectin was indicative of patient status.Conclusion: Thus, we propose that serum BDNF content and BDNF/adiponectin ratio may serve as tools predicting worsened prognosis in COVID-19, especially for male patients.

Вплив лікування метформіном на вміст деяких гормонів жирової тканини та медіаторів генералізованого неспецифічного запалення в пацієнтів з уперше виявленим цукровим діабетом 2-го типу

Метою дослідження було вивчення впливу препарату метформін на рівень деяких гормонів жирової тканини та медіаторів генералізованого неспецифічного запалення при цукровому діабеті 2-го типу. Обстежено 38 пацієнтів з уперше виявленим цукровим діабетом 2-го типу перед початком і після 12 місяців цукрознижувальної монотерапії Глюкофажем. Отримані результати свідчать, що нормалізація показників вуглеводного обміну, зниження маси тіла пацієнтів на тлі проведеного лікування спричинено не лише прямим впливом метформіну на поліпшення поглинання глюкози периферичними тканинами, а і його здатністю модулювати секрецію адипоцитокінів.

Sestrin2 induction contributes to anti-inflammatory responses and cell survival by globular adiponectin in macrophages

Adiponectin, an adipose tissue-derived hormone, exhibits a modulatory effect on cell death/survival and possesses potent anti-inflammatory properties. However, the underlying molecular mechanisms remain elusive. Sestrin2, a stress-inducible metabolic protein, has shown cytoprotective and inflammation-modulatory effects under stressful conditions. In this study, we examined the role of sestrin2 signaling in the modulation of cell survival and inflammatory responses by globular adiponectin (gAcrp) in macrophages. We observed that gAcrp induced a significant increase in sestrin2 expression in both RAW 264.7 murine macrophages and primary murine macrophages. Notably, gAcrp treatment markedly increased expression of hypoxia inducible factor-1 α (HIF-1α) and gene silencing of HIF-1α blocked sestrin2 induction by gAcrp. In addition, pretreatment with a pharmacological inhibitor of ERK or PI3K abrogated both sestrin2 and HIF-1α expression by gAcrp, indicating that ERK/PI3K-mediated HIF-1α signaling pathway plays a critical role in sestrin2 induction by gAcrp. Furthermore, sestrin2 induction is implicated in autophagy activation, and knockdown of sestrin2 prevented enhanced cell viability by gAcrp. Moreover, gene silencing of sestrin2 caused restoration of gAcrp-induced expression of anti-inflammatory genes in a gene-selective manner. Taken together, these results indicate that sestrin2 induction critically contributes to cell survival and anti-inflammatory responses by gAcrp in macrophages.

Adipokines as Immune Cell Modulators in Multiple Sclerosis

Multiple sclerosis (MS), a chronic inflammatory and demyelinating disease of the central nervous system (CNS), is a major clinical and societal problem, which has a tremendous impact on the life of patients and their proxies. Current immunomodulatory and anti-inflammatory therapies prove to be relatively effective; however, they fail to concomitantly stop ongoing neurological deterioration and do not reverse acquired disability. The proportion to which genetic and environmental factors contribute to the etiology of MS is still incompletely understood; however, a recent association between MS etiology and obesity was shown, with obesity greatly increasing the risk of developing MS. An altered balance of adipokines, which are white adipose tissue (WAT) hormones, plays an important role in the low-grade chronic inflammation during obesity by their pervasive modification of local and systemic inflammation. Vice versa, inflammatory factors secreted by immune cells affect adipokine function. To explore the role of adipokines in MS pathology, we will here review the reciprocal effects of adipokines and immune cells and summarize alterations in adipokine levels in MS patient cohorts. Finally, we will discuss proof-of-concept studies demonstrating the therapeutic potential of adipokines to target both neuroinflammation and neurodegeneration processes in MS.

Study of Circulating Apelin in Type 1 Diabetic Patients and its Association with Glycemic Control in a Group of Egyptian Population

Abstract Background Type 1 diabetes mellitus (T1DM) is one of the most common chronic and metabolic diseases worldwide. The incidence of T1DM is reported to be increasing by 3-5% per year, and the number of people with diabetes is estimated to reach 380 million by 2025. Several studies have shown that TIDM is associated with metabolic abnormalities and alteration of adipose tissue hormones (adipokines). Apelin, one of the most abundantly expressed adipocytokine, is a bioactive peptide and produces its effects through a cell surface G protein-coupled receptor called APJ.The apelinergic system, is involved in a wide range of functions including regulation of body fluid homeostasis, cardiovascular system, angiogenesis and energy metabolism . Additionally, apelin participates in pathological processes, including obesity and diabetes. Apelin plays a beneficial role in energy metabolism. Objectives The aim of this study is to evaluate serum Apelin levels in patients with type 1 diabetes and to correlate the serum Apelin level and glycemic control. Patients and Methods This study was a cross sectional study. Participants were classified into two groups. The first group included 60 patient with T1DM recruited from Ain Shams University Endocrinology and Diabetes outpatient clinics in Cairo during the period from June 2019 to January2002 and the second group included 40 healthy controls. Serum apelin (APLN), FBS, 2hrPP, HbA1c, lipid profile and eGDR were measured for each case. Results Comparison between T1DM patients and controls revealed that serum apelin levels, were significantly increased in cases compared to controls. Negative correlations were found between Apelin and HbA1c% in the diabetic group as a marker for glycemic control so apelin may have a promising role as biomarkers in T1DM. Conclusion Our study showed that apelin concentrations were increased in type 1 diabetic patients compared to healthy controls. The potential association of apelin with insulin secretion and action may reveal new pathways in the pathogenesis of type 1 diabetes. Apelin in T1DM patients may be considered as promising adipokines for predicting glycemic control.

Синдром полікістозних яєчників у щоденній практиці

Синдром полікістозних яєчників (СПКЯ) — системна патологія, при якій порушуються всі ланки ендокринної системи, а не лише функція яєчників. СПКЯ трапляється у жінок будь-якого віку, розпочинаючи від пубертатного періоду і до менопаузи, із залученням у процес майже всіх органів і систем організму. СПКЯ виявляють у 6–19 % жінок репродуктивного віку. На СПКЯ припадає більш ніж половина всіх випадків ендокринного безпліддя (50–75 %) і близько 20–22 % причин безплідного шлюбу взагалі. Основними клінічними ознаками СПКЯ є гіперандрогенія, менструальна й/або овуляторна дисфункція та полікістозна морфологія яєчників. У жінок, яким виставлений цей діагноз, значно вищий ризик розвитку серцево-судинних захворювань, цукрового діабету, злоякісних новоутворень малого тазу, мастопатії та раку молочної залози. У патогенезі синдрому велике значення мають гландулярна й екстрагландулярна гіперандрогенія, інсулінорезистентність, гіпофізарна дисфункція, генетичні порушення та порушення продукції гормонів жирової тканини. Основна мета діагностики СПКЯ — визначення ступеня тяжкості клінічних проявів, джерела та патогенезу гіперпродукції андрогенів, впливу на репродуктивну функцію, оцінка метаболічних і кардіоваскулярних ризиків. Диференційна діагностика скерована на виключення захворювань щитоподібної залози, гіперпролактинемії та некласичної вродженої дисфункції кори надниркових залоз. На сьогодні все більше уваги приділяється комплексному підходу до лікування порушень, що виникають у пацієнток з СПКЯ, з урахуванням їх віку, репродуктивних планів і стану гормонального фону. Важливим є не тільки відновлення фертильності та досягнення косметичних ефектів, але й профілактика пізніх метаболічних порушень.

THE RELATIONSHIP BETWEEN METABOLIC DISORDERS AND TUMOR PROGRESSION: REVIEW OF PRESENT DATA AND NEW THERAPEUTIC TARGETS

Background. Type 2 diabetes mellitus, obstructive sleep apnea, osteoarthritis and certain types of cancer are known to correlate with obesity. The mechanisms underlying the link between metabolic disorders and cancer remain obscure, yet assuming a potentially important role of reduced insulin sensitivity, altered glucose metabolism in tumor cells (the so-called Warburg effect), changes in the spectrum of secreted adipokines or interaction with their cognitive receptors as well as changes in steroid sex hormone production.Material and methods. A search for articles published in peer-reviewed journals indexed in pubmed, Wos, scopus and Rsci was carried out. More than 150 articles devoted to the study of the relationship between metabolic disorders and tumor progression were analyzed, of which 69 were included in this review.Results. The main strategy of anticancer therapy is to suppress the proliferation of tumor cells and metastasis. However, one should take into consideration a significant role of additional factors that can enhance side effects of anticancer therapy, ensure the resistance of tumor cells to chemotherapy or change cancer cell metabolic profile. New data recently emerging in the literature indicate an important function of proteins such as t-cadherin and urokinase receptor (upar) and their possible involvement in the regulation of tumor cell metabolism, in particular, sensitivity to insulin and adipose tissue hormones. The review encompasses recent data on the involvement of t-cadherin and upar in the regulation of metabolism and proposes a model explaining the relationship between these proteins and metabolic disorders associated with the processes of carcinogenesis and chemoresistance of cancer cells.Conclusion. Understanding of the factors and mechanisms that support obesity and metabolic disorders is relevant both for the development of cancer preventive measures and optimization of therapeutic strategies for combating cancer.

FREQUENCY OF EXACERBATIONS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AS ONE OF THE FACTORS OF PROGRESSION OF NON-ALCOHOLIC FATTY LIVER DISEASE

This article presents the results of studies obtained by observing patients with non-alcoholic fatty liver disease (NAFLD) on the background of chronic obstructive pulmonary disease (COPD). As a result of the analysis it was found that the frequency of exacerbations of COPD with hospitalization in overweight patients in the presence of NAFLD leads to increased imbalance of adipose tissue hormones in the form of decreased adiponectin and increased leptin, and correlates with impaired lipid metabolism and severe grade of hepatic steatosis. In patients with frequent exacerbations, there is a significant positive correlation between leptin levels and TNF-a factor, which may be associated with an increase in overall inflammation. The revealed imbalance of adiponectin and leptin content in patients with COPD with overweight is a factor in the progression of NAFLD.

Obesity is the basis of metabolic syndrome

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.

Ожирение — основа метаболического синдрома

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.