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The factors promoting development of non-alcoholic fatty liver disease in patients with obesity and different state of carbohydrate metabolism have been studied. 43 patients were examined; these included 26 patients with abdominal obesity (BMI=52.9±7.9 kg/m2). The control group consisted of 17 conditionally healthy donors without obesity (BMI=18.9-24.9 kg/m2), seven of them formed a comparison group that was included to compare the results of study on the levels of tissue-specific expression of HSP70 mRNA. The study of mRNA expression was performed by real-time PCR. The concentration of IL-6 and TNF-a was measured in blood serum by the ELISA method. In patients with obesity with diabetes mellitus type 2 (DM2), a significant increase in the serum level of proinflammatory cytokines was found in comparison with the group of patients without DM2 and control. The results of histological examination of liver biopsy specimens in obese patients revealed the most pronounced changes in the group of DM2 patients. Regardless of the stage of nonalcoholic fatty liver disease in obese DM2 patients, an increase in the area of fatty inclusions (relative to the group without type 2 diabetes) was recorded. The study of the HSP70 gene expression in peripheral blood mononuclear cells allowed its significant increase relative to the comparison group. The relationship between the level of expression of the HSP70 gene in metabolically active tissues (visceral, subcutaneous adipose tissue and liver) established in all obese patients with the serum content of proinflammatory cytokines (IL-6 and TNF-a) may indicate suppression of HSP70 expression in these tissues, background of systemic and local inflammation in obesity.

Chemerin is a mediator of adipose tissue involved in the regulation of many processes, including lipogenesis, and inflammatory response. The role of chemerin in the development of insulin resistance has been insufficiently studied and needs detailed understanding. The aim of the study was to investigate chemerin production in obese patients with different states of carbohydrate metabolism. The study included 155 patients with a diagnosis of obesity; 34 patients with overweight. The control group 1 consisted of 43 conditionally healthy donors who did not have obesity. For comparison of the results of a study to determine the levels of tissue-specific mRNA expression of the genes IL-6, TNF-a, RARRES2, (encoding IL-6, TNF-a and chemerin) in adipose tissue introduced a control group 2 - 30 patients without obesity. Study on the relative level of mRNA expression of the genes IL-6, TNF-a and RARRES2 (encoding IL-6, TNF-a and chemerin) was carried out using real time PCR. Concentrations of IL-6, TNF-a, and chemerin were measured in serum/plasma using an enzyme-linked immunosorbent assay (ELISA). We found significant differences in the plasma level of chemerin and tissue-specific features of RARRES2 gene expression in obese patients, depending on the degree of obesity and the state of carbohydrate metabolism. Multidirectional associations of RARRES2 gene expression with TNF-a and IL-6 genes in adipose tissues of different localization are shown: in obese patients (BMI £40 kg/m2) without type 2 diabetes - negative, and type 2 diabetes - positive. Identified relationship chemerin plasma content and the expression level of its gene in biopsies with various parameters of carbohydrate and lipid metabolism, proinflammatory molecules indicate chemerin involved in metabolic and immune processes in obesity.

We investigated the tissue-specific features of the production of adipokines (leptin and adipsin) by adipose tissue in obese patients depending on the degree of obesity and the state of carbohydrate metabolism. An increase in the content of adipsin and leptin in the blood plasma was found. In patients with varying degrees of obesity with and without type 2 diabetes mellitus (DM 2), we determined the level of tissue-specific expression of LEP and CFD genes encoding leptin and adipsin, respectively. The contribution of different adipose tissue depots to the blood plasma level of adipsin and leptin in obese patients with and without DM 2 was established. The disturbance of reciprocal relationships between adipsin and leptin in obesity is associated with the development of insulin resistance.

In this review we discuss the molecular mechanisms of insulin resistance concomitant with metabolic inflammation. We also analyze the world results of experimental and clinical studies which aimed at identifying the molecular targets for the development of new prevention and treatment of insulin resistance.