ЦЕЛЬ: провести анализ уровней экспрессии микроРНК-222-3p, микроРНК-423-5p и генов NRG4 и ERBB4 у больных ожирением с/без сахарного диабета (СД) 2 типа. МАТЕРИАЛЫ И МЕТОДЫ: в комплексном исследовании приняли участие 70 обследуемых лиц. Группу с ожирением без СД 2 типа составили 25 пациентов (индекс массы тела (ИМТ) = 41,5±6,5 кг/м2, возраст 39±2 лет); с СД 2 типа – 25 пациентов (ИМТ=47,1±8,7 кг/м2, возраст 46±8лет) и 20 условно здоровых доноров (ИМТ = 22,5±2,6 кг/м2, возраст 36±9 лет). Материалом для исследования явились образцы плазмы крови и биоптаты печени. Определение уровня микроРНК-222-3p, микроРНК-423-5p в плазме крови осуществля- лось методом ПЦР в режиме реального времени c помощью амплификатора Biorad CFX-96. РЕЗУЛЬТАТЫ: уровень экспрессии микроРНК-423-5p у больных ожирением с СД 2 типа в плазме кро- ви был достоверно повышен относительно больных ожирением и условно здоровых доноров. Тогда как у больных с ожирением без СД 2 типа в биоптатах печени было обнаружено повышение экспрессии микроРНК-423-5p. Уровень экспрессии микроРНК-222-3p в плазме крови достоверно не отличался в исследуемых группах. Напротив, в биоптатах печени было зафиксировано повышение экспрессии микроРНК-222-3p у боль- ных ожирением без СД 2 типа относительно условно здоровых доноров и больных СД 2 типа. У больных ожирением с СД 2 типа попарное сравнение уровня экспрессии микроРНК-423-5p и микроРНК-222-3p выявило его значительное повышение в плазме крови относительно ткани печени. У больных без СД 2 типа уровень экспрессии гена ERBB4 и NRG4 в печени достоверно снижался только относительно условно здоровых доноров. У больных ожирением с СД 2 типа, напротив, уровень экспрессии гена ERBB4 в печени снижался, а значения NRG4 были сопоставимы с контролем. ВЫВОДЫ: 1. У больных ожирением без СД 2 типа уровень экспрессии микроРНК-423-5p в печени повышен, тогда как экспрессия генов мишеней – NRG4 и ERBB4 – снижена относительно условно здоровых доноров. 2. Выход микроРНК-222-3p и микроРНК-423-5p в системный кровоток свидетельствует о дисфункции пе- чени у больных ожирением с СД 2 типа. Исследование на клеточной модели неалкогольной жировой болезни печени (НАЖБП) или стеатогепа- тита и расширение выборки пациентов позволят получить подкрепление нашей гипотезы.

Obesity is the main cause of metabolic complications. Fatty liver infiltration is a companion of obesity. NAFLD is associated with impaired energy metabolism with an excess of nutrients. Mitochondrial dynamics are important for the regulation of energy balance, which regulates mitochondrial function, apoptosis, and mitophagy. The aim of this study was to investigate the effect of gp130 on the components of mitochondrial dynamics in a cellular model of steatohepatitis. Addition of IL-6/gp130 contributed to an increase in the percentage of live cells and a decrease in the percentage of dead and apoptotic cells. Addition of IL-6/gp130 increased the expression of NF-kB1 gene and mitochondrial dynamics markers (MFN2 and TFAM) in HepG2 with tBHP/Oleic. Addition of IL-6 or gp130 reduced the expression of cytoprotector genes (HSF1 and HSP70) in HepG2 cell cultures with tBHP/Oleic. Increased mitochondrial dynamics gene activity protected against HepG2 cell death in the steatohepatitis model. Trans-signaling resulted in increased TFAM and MAPLC3B, and decreased DNM1L gene expression in HepG2 with tBHP/Oleic.

ЦЕЛЬ: провести анализ уровней экспрессии микроРНК-222-3p, микроРНК-423-5p и генов NRG4 и ERBB4 у больных ожирением с/без сахарного диабета (СД) 2 типа. МАТЕРИАЛЫ И МЕТОДЫ: в комплексном исследовании приняли участие 70 обследуемых лиц. Группу с ожирением без СД 2 типа составили 25 пациентов (индекс массы тела (ИМТ) = 41,5±6,5 кг/м2, возраст 39±2 лет); с СД 2 типа – 25 пациентов (ИМТ=47,1±8,7 кг/м2, возраст 46±8лет) и 20 условно здоровых доноров (ИМТ = 22,5±2,6 кг/м2, возраст 36±9 лет). Материалом для исследования явились образцы плазмы крови и биоптаты печени. Определение уровня микроРНК-222-3p, микроРНК-423-5p в плазме крови осуществля- лось методом ПЦР в режиме реального времени c помощью амплификатора Biorad CFX-96. РЕЗУЛЬТАТЫ: уровень экспрессии микроРНК-423-5p у больных ожирением с СД 2 типа в плазме кро- ви был достоверно повышен относительно больных ожирением и условно здоровых доноров. Тогда как у больных с ожирением без СД 2 типа в биоптатах печени было обнаружено повышение экспрессии микроРНК-423-5p. Уровень экспрессии микроРНК-222-3p в плазме крови достоверно не отличался в исследуемых группах. Напротив, в биоптатах печени было зафиксировано повышение экспрессии микроРНК-222-3p у боль- ных ожирением без СД 2 типа относительно условно здоровых доноров и больных СД 2 типа. У больных ожирением с СД 2 типа попарное сравнение уровня экспрессии микроРНК-423-5p и микроРНК-222-3p выявило его значительное повышение в плазме крови относительно ткани печени. У больных без СД 2 типа уровень экспрессии гена ERBB4 и NRG4 в печени достоверно снижался только относительно условно здоровых доноров. У больных ожирением с СД 2 типа, напротив, уровень экспрессии гена ERBB4 в печени снижался, а значения NRG4 были сопоставимы с контролем. ВЫВОДЫ: 1. У больных ожирением без СД 2 типа уровень экспрессии микроРНК-423-5p в печени повышен, тогда как экспрессия генов мишеней – NRG4 и ERBB4 – снижена относительно условно здоровых доноров. 2. Выход микроРНК-222-3p и микроРНК-423-5p в системный кровоток свидетельствует о дисфункции пе- чени у больных ожирением с СД 2 типа. Исследование на клеточной модели неалкогольной жировой болезни печени (НАЖБП) или стеатогепа- тита и расширение выборки пациентов позволят получить подкрепление нашей гипотезы.

Obese individuals are at high risk for developing type 2 diabetes mellitus, cardiovascular diseases, and nonalcoholic fatty liver disease. The aim of this review was to analyze the scientific literature and databases to reveal the fundamental role of neuregulin 4 (NRG4) and its receptors in the development of obesity-associated metabolic disorders. This review demonstrates that NRG4 and its receptors are promising therapeutic targets for the treatment of socially significant obesity-associated pathologies. The review contains nine chapters. Information on the structure of ERBB4 and NRG4 splice isoforms and subsequent activation of downstream targets is presented. The tissue-specific features of the NRG4 and ERBB4 genes and protein production are also highlighted. The role of NRG4 and ERBB3/4 in the pathophysiological mechanisms of the development of metabolic disorders in obesity is discussed in detail. The final chapter of the review is devoted to the miRNA-dependent regulation of NRG4 and ERBB4. Recent studies have shown that several miRNAs regulate ERBB4 expression, but no information was found on the interaction of NRG4 with miRNAs. We now demonstrate the putative relationships between NRG4 and let-7a-5p, let-7c-5p, miR-423-5p, miR-93-5p, miR-23a-3p, and miR-15b-5p for the first time. In addition, we found SNP mutations affecting the interaction of NRG4 and ERBB4 with miRNA in these genes as well as in miRNAs. In summary, this review provides a detailed and comprehensive overview of the role of NRG4 in obesity-associated metabolic disorders. The review summarizes all current studies on this topic and opens perspectives for future research.

Obesity and type 2 diabetes mellitus (T2DM) are global epidemics at the present time, being a serious public health issue. An increased prevalence in the number of obese people promotes a risk for developing cardiovascular diseases (CVD) and some types of cancer. The ErbB signaling pathway plays a significant role in development of the disorders associated with metabolic dysfunction (e.g., T2DM, obesity, arterial hypertension). Neuregulin 4 (NRG4) is a new adipokine with similar effects to adiponectin. Interaction between the ErbB3, ErbB4 receptors and their ligand, NRG4, launches the processes required to maintain the energy balance in the cells. There are controversial literature data on NRG4 levels in blood circulation. In particular, the existing data concerning functions / mechanism of NRG4 action has been obtained in experimental animals and cell lines, which is not always reproducible in humans. According to some works, liver may be the key target organ for NRG4. The present article is devoted to assessment of relationships between the NRG4 level in blood, and the parameters of carbohydrate and lipid metabolism, as well as presence of diseases associated with obesity. The study included obese patients with and without type 2 diabetes. The content of NRG4, indices of carbohydrate and lipid metabolism in the blood was assessed by means of enzyme immunoassay and biochemical techniques, respectively. It was found that the level of NRG4 was increased in obese patients with T2DM compared with healthy donors, and obese patients without T2DM. Statistical evaluation by correlation and regression analysis revealed numerous relationships between NRG4 and the parameters of lipid and carbohydrate metabolism, as well as some correlations between the NRG4 levels and clinical disorders associated with obesity (type 2 diabetes and arterial hypertension). Thus, NRG4 may be involved into the development of dyslipidemia in obese patients. We consider an increase of blood NRG4 levels in obese patients with type 2 diabetes as a compensatory response to the increased insulin-mediated lipogenesis. The data obtained are important in search for new points of influence upon pathogenesis of diseases associated with metabolic disorders. Neuroregulin 4 and its receptors may be promising targets for the treatment of socially significant clinical disorders.

Биогенез митохондрий регулируется организованной индукции нескольких транскрипционных факторов. Утрата митохондриальной адаптации способствует сахарному диабету 2 типа. Высокий уровень IL-6 в плазме крови пациентов с ожирением взаимосвязан со снижением экспрессии гена TFAM в биоптатах печени. Уровень экспрессии гена TFAM в биоптатах печени у больных с СД 2 типа снижался относительно контрольной группы. Mitochondrial biogenesis is regulated by the organized induction of several transcription factors. Loss of mitochondrial adaptation contributes to type 2 diabetes. A high level of IL-6 in the blood plasma of obese patients is associated with a decrease in TFAM gene expression in liver biopsies. The expression level of the TFAM gene in liver biopsies of patients with type 2 diabetes decreased relative to the control group.

Высокий уровень TNFSF13 в плазме крови пациентов с ожирением взаимосвязан с митохондриальным делением - увеличение экспрессии гена DNM1L в жировой ткани большого сальника. У больных ожирением с СД 2 типа продукции белка DRP1 повышена в подкожной жировой ткани по сравнению со значениями у пациентов с ожирением без СД 2 типа. The high level of TNFSF13 in the blood plasma of obese patients is associated with mitochondrial fission - an increase in the expression of the DNM1L gene in the adipose tissue of the greater omentum. In obese patients with type 2 diabetes, the production of DRP1 protein is increased in subcutaneous adipose tissue compared with the values in obese patients without type 2 diabetes.

Митохондриальная динамика объединяет под собой понятие непрерывного деления и слияния митохондрий и определяет митохондриальную архитектуру. TNF-a в плазме крови отрицательно взаимосвязан с экспрессией гена MFN2 в висцеральной жировой ткани. Повышение экспрессия гена MFN2 в жировой ткани может быть защитным механизмом для поддержания нормальной митохондриальной динамики в жировой ткани у пациентов с ожирением без СД 2 типа. Mitochondrial dynamics brings together the concept of continuous mitochondrial fission and fusion and defines mitochondrial architecture. Plasma TNF-a is negatively associated with MFN2 gene expression in visceral adipose tissue. Increased expression of the MFN2 gene in adipose tissue may be a protective mechanism for maintaining normal mitochondrial dynamics in adipose tissue in obese patients without type 2 diabetes.

Autophagy is required to maintain cellular homeostasis and organ function by selectively ridding cells of potentially toxic proteins, lipids, and organelles. Impaired homeostasis of autophagic processes is associated with metabolic disorders such as obesity and type 2 diabetes mellitus. In obesity, a violation of autophagy in adipose tissue and its inflammation contributes to the formation of type 2 diabetes mellitus. The aim of the study was to analyze the expression of autophagy genes in the adipose tissue of the greater omentum and to search for their relationship with the levels of cytokines of the IL-10 family in blood plasma in obese patients, depending on the presence or absence of type 2 diabetes mellitus. Blood plasma and visceral adipose tissue samples were studied from 347 obese patients with and without type 2 diabetes. A biochemical analysis of the patients' blood was carried out. The level of cytokines was detected by flow fluorometry. Gene expression was determined by real-time PCR, and tissue-specific protein production was determined by immunoblotting. Statistical processing of the results was carried out using GraphPad Prism 9.0.0 software. Plasma levels of IL-10, IL-20, IL-22, IL-28A, and IL-29 are increased in obese patients without type 2 diabetes compared with patients with type 2 diabetes. In patients with type 2 diabetes mellitus, the expression of the SQSTM1_p62 and MAP1LC3B genes in the greater omentum increased compared to patients without it. High plasma levels of IL-22 and IL-26 are associated with the presence of type 2 diabetes mellitus. In patients without type 2 diabetes mellitus, an increase in the level of IL-28A in blood plasma is associated with a decrease in the expression of autophagy genes SQSTM1_p62 and MAP1LC3B in the adipose tissue of the greater omentum.

Interactions between receptors and ligands of the tumor necrosis factor superfamily (TNFSF) provide costimulatory signals that control the survival, proliferation, differentiation, and effector function of immune cells. All components of the TNF superfamily are associated with NF-kB functions that are not limited to cell death and may promote survival in the face of adipose tissue inflammation in obesity. Inflammation dysfunction of mitochondria is a key factor associated with insulin resistance in obesity. The aim of the study was to analyze the relationship of soluble forms of receptors and ligands of the TNF superfamily in blood plasma with mitochondrial dynamics in adipose tissue (greater omentum (GO) and subcutaneous adipose tissue (Sat)) of obese patients with and without type 2 diabetes mellitus (T2DM). Increased plasma sTNF-R1, sTNF-R2, sTNFRSF8 receptors, and ligands TNFSF12, TNFSF13, TNFSF13B are characteristic of obese patients without T2DM. The TNF-a levels in blood plasma were associated with a decrease in MFN2 gene expression in GO and IL-10 in blood plasma. The TNFSF12 levels contributed to a decrease in glucose levels, a decrease in BMI, and an increase in IL-10 levels by influencing the MFN2 gene expression in GO, which supports mitochondrial fusion.

Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common chronic liver diseases worldwide, affecting 25% of the world population. In recent years, there has been increasing evidence for the involvement of microRNAs in the epigenetic regulation of genes taking part in the development of steatosis and steatohepatitis—two main stages of NAFLD pathogenesis. In the present study, miRNA profiles were studied in groups of patients with steatosis and steatohepatitis to compare the characteristics of RNA-dependent epigenetic regulation of the stages of NAFLD development. According to the results of miRNA screening, 23 miRNAs were differentially expressed serum in a group of patients with steatohepatitis and 2 in a group of patients with steatosis. MiR-195-5p and miR-16-5p are common differentially expressed miRNAs for both steatosis and steatohepatitis. We analyzed the obtained results: the search for target genes for the differentially expressed miRNAs in our study and the subsequent gene set enrichment analysis performed on KEGG and REACTOME databases revealed which metabolic pathways undergo changes in RNA-dependent epigenetic regulation in steatosis and steatohepatitis. New findings within the framework of this study are the dysregulation of neurohumoral pathways in the pathogenesis of NAFLD as an object of changes in RNA-dependent epigenetic regulation. The miRNAs differentially expressed in our study were found to target 7% of genes in the classic pathogenesis of NAFLD in the group of patients with steatosis and 50% in the group of patients with steatohepatitis. The effects of these microRNAs on genes for the pathogenesis of NAFLD were analyzed in detail. MiR-374a-5p, miR-1-3p and miR-23a-3p do not target genes directly involved in the pathogenesis of NAFLD. The differentially expressed miRNAs found in this study target genes largely responsible for mitochondrial function. The role of miR-423-5p, miR-143-5p and miR-200c-3 in regulating apoptotic processes in the liver and hepatocarcinogenesis is of interest for future experimental studies. These miR-374a, miR-143, miR-1, miR-23a, and miR-423 have potential for steatohepatitis diagnosis and are poorly studied in the context of NAFLD. Thus, this work opens up prospects for further studies of microRNAs as diagnostic and therapeutic biomarkers for NAFLD.

In obese patients, the relationship between the content of chemerin in blood plasma and the expression of genes TFAM, Drp1, MFN2, SOD, BAX, responsible for quality control of mitochondria, in insulin-dependent tissues (adipose tissue, liver) was revealed. The tissue-specific features of gene expression (TFAM, Drp1, MFN2, SOD, BAX), the number of mtDNA copies in the studied depots in obese patients were established. It has been proven that a change (decrease) in the number of mtDNA copies in insulin-dependent tissues can have a protective effect on mitochondria under conditions of increased oxidative stress. It was found that in patients without type 2 diabetes, an increase in chemerin production promotes the activation of the antioxidant system in the visceral adipose tissue but not in the liver. On the contrary, all obese patients with type 2 diabetes showed a decrease (compared with patients without type 2 diabetes) in the plasma level of chemerin. Thus, the low content of chemerin in the blood plasma in patients with type 2 diabetes mediates the formation of mitochondrial dysfunction in insulin-dependent tissues (adipose tissue, liver).

Обсуждаются механизмы патофизиологических процессов, ассоциированных с нарушениями метаболизма. Анализируются патофизиологические механизмы развития нарушений обмена веществ при абдоминальном ожирении, сахарном диабете 2-го типа. Систематизированы клинико-лабораторные показатели этих заболеваний, описаны современные методы их лечения: терапевтические и хирургические. Отдельно представлены основные клинико-лабораторные методы исследования, необходимые для диагностики, прогнозирования и мониторинга ассоциированных с ожирением патологий. В пособие включена практическая часть, в ходе работы над которой можно освоить описанные методики и закрепить изученный материал. Разработано в соответствии с рабочей программой дисциплины «Патологическая физиология» и предназначено для студентов медицинских вузов и слушателей ФПК, аспирантов и студентов биологических факультетов.

Steatosis in the liver in obesity increases the work of mitochondria to utilize excess lipids. An overload of β-oxidation of fatty acids, the tricarboxylic acid cycle, and oxidative phosphorylation leads to a decrease in ATP and an increase in the formation of reactive oxygen species. Normally, mitochondria can efficiently remove elevated levels of reactive oxygen species using the cell's antioxidant system and metabolic adaptation to altered conditions. This study aimed to investigate the role of hepatic SOD expression in the pathogenesis of NAFLD in obesity. It was found that the level of SOD1 expression in the liver in obese patients with and without type 2 diabetes with a BMI > 40 kg/m2 was lower than in healthy donors. The copy number of mitochondrial DNA (mtDNA) in the liver in all obese patients was more than two times lower than in the control group. In the liver of obese patients without type 2 diabetes, the SOD1 protein level and the mtDNA copy number were interrelated and negatively correlated with the area of fatty inclusions. Thus, in obese patients, a decrease in antioxidant defense in the liver leads to the vulnerability of mitochondria, which, in turn, contributes to the progression of steatosis and insulin resistance.

Background. The pathogenesis of nonalcoholic fatty liver disease (NAFLD), which develops in obesity and type 2 diabetes mellitus (T2DM), is associated with the effects of inflammatory factors on the liver parenchyma and liver mitochondrial dysfunction. Aim. To determine the role of sTNFSF14 in the regulation of liver mitochondrial biogenesis in obese patients with and without T2DM. Materials and methods. The study included 263 obese patients with and without T2DM and 42 apparently healthy donors. Quantitative determination of cytokines in the blood plasma was performed by fluorescence flow cytometry. The level of relative gene expression in the liver biopsy samples was investigated by real-time PCR. Semi-quantitative determination of proteins in the liver biopsy samples was studied by western blotting. Results. The study showed that the levels of sTNFSF14, interleukin (IL)-10, gp130 / sIL-6Rb, and sIL-6Ra in the blood plasma of the obese patients without T2DM significantly exceeded the similar values in the control patients and obese patients with T2DM. In the liver biopsy samples of the obese patients with T2DM and a body mass index (BMI) > 40 kg / m2, the expression level of the dynamin-1-like protein (DRP1 / DNM1L) gene was lower than in the control group, and the expression level of the mitofusin 2 (MFN2 ) gene tended to be higher. Compared with the control group, an increase in the expression level of the NADH-ubiquinone oxidoreductase chain 4 (MT-ND4) gene was recorded in the liver of all the obese patients. The patients with obesity showed a decrease in the amount of mitochondrial DNA (mtDNA) compared with the control group. Conclusion. Thus, sTNFSF14, interacting with IL-10 and gp130 / sIL-6Rb in the circulation, positively effects the liver in the obese patients without T2DM. A low level of sTNFSF14 in the blood plasma of the obese patients with T2DM results in decreased mitochondrial division and increased cellular respiration.

Interactions between receptors and ligands of the tumor necrosis factor superfamily (TNFSF) provide costimulatory signals that control the survival, proliferation, differentiation, and effector function of immune cells. All components of the TNF superfamily are associated with NF-kB functions that are not limited to cell death and may promote survival in the face of adipose tissue inflammation in obesity. Inflammation and pro-inflammatory dysfunction of mitochondria are key factors associated with insulin resistance in obesity. The aim of the study was to analyze the relationship of soluble forms of receptors and ligands of the TNF superfam-ily in blood plasma with mitochondrial dynamics in adipose tissue (greater omentum (GO) and subcutaneous adipose tissue (Sat)) of obese patients with and without type 2 diabetes mellitus (T2DM). Increased plasma sTNF-R1, sTNF-R2, sTNFRSF8 receptors and ligands TNFSF12, TNFSF13, TNFSF13B are characteristic of obese patients without T2DM. Increases in TNFSF12, TNFSF13B, and sTNF-R1 levels are associated with decreased glucose concentration and decreased BMI in obese patients. The gene expression levels responsible for regulating mitochondrial dynamics were increased in obese patients without T2DM and were unbalanced in patients with obesity and T2DM.

Type 2 diabetes mellitus (T2DM) is one of the most prominent and socially significant problems. The present study aimed to identify the mechanisms of interaction of critical regulators of carbohydrate metabolism using bioinformatics and experimental methods and to assess their influence on the development of T2DM. We conducted an in silico search for the relationship of hormones and adipokines and performed functional annotation of the receptors for ghrelin and incretins. Hormones and adipokines were assessed in the plasma of obese patients with and without T2DM as well as after laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) surgeries. Incretin- and ghrelin-associated functions and metabolic processes were discovered. Low ghrelin levels were observed in obese patients without T2DM compared with healthy volunteers and the other groups. The highest ghrelin levels were observed in obese patients with T2DM. This defense mechanism against insulin resistance could be realized through the receptors G-protein-coupled receptor (GPCR), growth hormone secretagogue receptor (GHSR), and growth hormone-releasing hormone receptor (GHRHR). These receptors are associated with proliferative, inflammatory, and neurohumoral signaling pathways and regulate responses to nutrient intake. Signaling through the GPCR class unites ghrelin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide (GLP)-1. Ghrelin impairs carbohydrate and lipid metabolism in obese patients. Ghrelin is associated with elevated plasma levels of insulin, glucagon, and leptin. Specific activation of receptors and modulation by posttranslational modifications of ghrelin can control IR's development in obesity, which is a promising area for research.

According to the world community, metabolic complications are associated with inflammation in obesity. The cytokines of the interleukins-6 (IL-6) family consist of IL-6, IL-11, IL-27 and have similar, but individual effects, such as the control of liver damage, the balance between metabolic status. IL-6 is ambiguous and has inflammatory properties, regenerative and anti-inflammatory effects. It was established that pathological effects are trained by signal transduction, and anti-inflammatory effects are trained by classical signal transduction. The purpose of the study was to evaluate the role of the IL-6 and his receptors sIL-6Ra, gp130/sIL-6Rb in the regulation of carbohydrate (glucose level) and lipid (cholesterol (Hol), low-density lipoprotein (LDL), triglycerides (TR), high-density lipoprotein (HDL)) exchanges in serum / plasma in patients with metabolic syndrome (MetS). This fact may indicate the protective role of sIL-6Ra trans-signaling and protective role of IL-6 signal inhibition due to high levels of sgp130 / sIL-6Rb in relation to metabolic disorders in obesity patients.