Medicine / 7. Clinical medicine

Parakhonsky A.P.

Kuban Medical Institute, Krasnodar, Russia

Metabolic disturbances in obesity and their correction

Obesity is often associated with various metabolic disorders, making it one of the most important health problems. In the life of a patient with obesity, a number of problems. Overweight is often restricts the mobility of people and impedes the process of self - physical problems. People with obesity are less attractive in appearance and are often subjected to on-laugh - the aesthetic and psychological problems. There are a variety of metabolic problems that arise because of inconsistencies between the availability energy and ability to accumulate it. The most serious of which may include non-alcoholic fatty liver disease (NAFLD), sugar diabetes (SD), hypertension with the gradual development of heart failure accuracy, dyslipidemia, sleep apnea, etc. Relationship of obesity with diabetes resulted in standing of insulin resistance depending on the individual's body fat. It is shown that the bases for the development of metabolic problems in people with obesity are two phenomena: insulin resistance and lipotoxicity. One of the mechanisms of this - a violation of the secretion of adipose tissue adipokines (adiponectin, resistin, vistafin) that regulate at insulin sensitivity. Another mechanism - increasing the secretion of chemokines by adipose tissue, which contributes to a macrophage activation and accumulation in adipose and muscle tissue.

Activated macrophages produce cytokines that adversely affect the sensitivity to insulin. Draws attention to the concept of limiting the ability of adipose tissue to increase its volume as a factor, conjugating obesity with metabolic syndrome and NAFLD. The factors influencing the capacity will expand to the adipose tissue are genetically programmed preadipocyte number, the program adipogenesis, vasculogenesis, with the spread-connective tissue, hypoxia. As part of this same concept is seen the value of the differences in the sets of nuclear receptors, expressed by the liver of healthy individuals or patients with NAFLD. In particular, the development of NAFLD can be promoted by a superfluous induction lipids of genetic programs of a primary fatty fabric in a liver. Based on the hypothesis of limiting adipose tissue expansion can be attributed to the phenomenon of massive obesity is not accompanied by a characteristic time duration of metabolic disorders. Draws attention to the concept takes into account the value of specific types of lipids in the development of metabolic by-violations in the liver, in particular insulin resistance. Accumulation three-glytserids may reflect the increase in lipid load, and regarded as of positive adaptation effect, which increases the buffering capacity of the liver to relatively ensure a sufficient supply of energy in a less toxic form. Identification the spectra lipids specific to each body is key information for working out of therapeutic actions. In the insulin resistance glucose ceases to be a major source of energy. This leads to the activation of lipolysis and the formation of a large amount of fatty acids that have the potential toxicity and metabolic disorders in realizing the target organs. At relative insufficiency β-cells pancreas cages tolerance to glucose is broken, and then the diabetes develops. Changes of lipid profile with increased lipoproteins low density and very low density, promoting the development of atherosclerosis. Liver in the process of stands as one of the main target organs, and hepatomegaly in obese due to accumulation of fat due to its expansion from natural sources, as well as the fact that the rate of apoptosis of hepatocytes yields the rate of their proliferation. Sequentially or simultaneously, by increasing the production of free radicals, oxidative stress develops, which leads to further changes in the form of nonalcoholic steatohepatitis (NASH).

New data in the study of the pathogenesis of metabolic disorders-profit in obesity suggest changes in the understanding of therapeutic interventions. In addition to weight loss is necessary to consider intermediate steps. This is - treatment of resistance at insulin, NAFLD, reducing the number of episodes of apnea during the night, drop in blood pressure, increasing the motilities of the joints, etc. A significant reduction in body weight combined, as a rule, resolution or better control of concomitant diseases. It is revealed that visceral adipose tissue is more associated with insulin resistance and increased cardiovascular risk, whereas the sub-cutaneous fat is metabolically more neutral. In this aspect it is necessary glitazones products characterized by their ability to retain fat within adipose tissue. Through increased lipogenesis they contribute to a decrease in the free fat acids in the blood, which increases the sensitivity of the liver to insulin, reduces steatosis and suppression of hepatic glucose production with a subsequent decrease of its content in the blood. Glitazones also reduce the concentration of circulating markers of cardiovascular risk and restoring inflammatory in the vascular wall, and reduce excretion of endothelin in the urine.

Another drug of choice - metformin, has no effect on the secretion of insulin, but has a number of extra pancreatic effects are reduced by the increased concentration of glucose in the blood. It improves tissue sensitivity to insulin, increases uptake of glucose by liver and muscle cells. Metformin leads to redistribution visceral fat that explains its favorable action on sensitivity of fabrics to insulin and a clinical course [2]. Silibinin - the most biologically active extract of Silibum marianum, inhibits adipocyte differentiation by decreasing the expression of genes, association, be initiated with adipogenesis [1]. In the experiment, installed it anti-inflammatory, anti-fibrogenic, antioxidant, hepatoprotective and hypoinsulinhaemie properties [3]. It is also shown that ursodeoxycholic acid can be used successfully in the treatment of NASH with a significant decrease in the active serum transaminases. Bile acids regulate the metabolism of glucose, and lipids, as are the natural ligands of nuclear farnezoide receptor and cell surface receptors. Results of and experimental researches which show significant efficacy of ursodeoxycholic acid in treatment of nonalcoholic steatohepatitis and major therapeutic potential of silibinin and silibinin/phosphatidylcholine complex at NAFLD were submitted. Thus, in most cases considerable reduction of weight of a body is combined with the permission or the best control over accompanying diseases.

Literature

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2. Moschetta A. / Joint EASL-AASLD Monothematic Conference “Nuclear Receptors and Liver Disease”, Vienna, Austria, 2009. – Program and Abstracts. - P. 27-29.

3. Trappoliere M. et al. Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells // J. Hepatol. – 2009. – Vol. 50, ¹ 6. – P. 1102-1111.