The syndrome of insulin resistance (IR) is one of the leading reasons for the increased risk of cardiovascular diseases and their complications. Among the key components of IR are obesity and dyslipidemia. Hydroxycitric acid (HCA), an inhibitor of a key enzyme of lipogenesis ATP citrate lyase (ACLY) is a promising obesity treatment agent. The aim of this work was to investigate the effect of HCA on lipid and lipoproteins content in the blood serum, as well as lipid content and activity of some lipid metabolism enzymes in the liver of hamsters with IR. IR was modeled by keeping animals on high-fat diet with addition of fructose. Lipid content was determined by using standard reagent kits, the level of lipoproteins, the activity of glucose 6-phosphate dehydrogenase and ACLY – spectrophotometrically, lysosomal lipase activity – fluorimetrically. Development of hyperlipidemia and atherogenic dyslipidemia, lipid accumulation in the liver, activation of lysosomal lipase and ACLY and reduction of glucose 6-phosphate dehydrogenase activity were shown under IR. The treatment by HCA reduces the manifestations of hyperlipidemia, but enhances the lipid accumulation in the liver.
Pathogenesis and clinical manifestations of metabolic syndrome (and other conditions characterized by the growth of fat mass and decreased adiponectin content) is associated with an imbalance of sex hormones, which develops under the influence of increased aromatase activity in adipose tissue. Drugs of the aromatase inhibitors therapeutic group are able to suppress the course of the aromatase reaction in the central and peripheral organs and tissues. The aim of our study was to establish the relationship between levels of serum adiponectin and adipose tissue aromatase avtivity in Syrian hamsters of different ages and gender with experimental metabolic syndrome and study the effect of aromatase inhibitors on these indicators. Experimental metabolic syndrome in animals was induced by a high-fat and fructose diet. The drugs were administered during the 21-st day in doses of 3.086 (exemestane), 0.309 (letrozole) and 0.126 mg/kg (anastrozole). The aromatase activity of the visceral adipose tissue was determined by the modified kinetic method based on the amount of the reaction product estradiol converted from testosterone. The content of estradiol in adipose tissue homogenate and serum adiponectin levels were measured by the immune enzyme method. The results showed a high inverse correlation between serum adiponectin and adipose tissue aromatase activity in hamsters. Aromatase inhibitors caused a decrease in the adipose tissue aromatase activity and increase in serum adiponectin levels. Letrazol demonstrated the greatest effect, it reduced aromatase activity in adipose tissue by 72-84% and increased serum adiponectin content by 1.6-1.8 times. At the same time, intra-group correlation of the studied parameters was significant. The results show the relationship between adiponectin level and adipose tissue aromatase activity and ability to change these rates by the way of aromatase inhibitors, which may be useful in clinical practice. Third-generation aromatase inhibitors are promising drugs for metabolic syndrome treatment and require further study in clinical trials. Вплив інгібіторів ароматази третього покоління на ароматазну активність вісцеральної жирової тканиниД. В. Литкін, А. Л. Загайко, Т. О. Брюханова Національний фармацевтичний університет, Харків, УкраїнаПатогенез та клінічні прояви метаболічного синдрому (та інших станів, що характеризуються зростанням жирової маси та зниженням вмісту адипонектину) асоційовані з дисбалансом статевих гормонів, який розвивається за впливу зростання активності ароматази в жировій тканині. Препарати групи інгібіторів ароматази здатні пригнічувати перебіг ароматазної реакції в центральних і периферичних органах і тканинах. Мета цього дослідженнявстановити взаємозв'язок між рівнем сироваткового адипонектину й ароматазною активністю жирової тканини на тлі експериментального метаболічного синдрому у сирійських хом'ячків різного віку та статі та вивчення впливу інгібіторів ароматази на ці показники. Експериментальний метаболічний синдром у тварин індукували дієтою з високим вмістом ж...
The unbalanced high-calorie diet can be the cause of a number of pathological states, including metabolic syndrome MS . It is well known that the risk of MS increases with age, but gender differences in age-related lipid metabolism changes under this pathology are not fully understood.In order to investigate the mechanisms of atherogenic dyslipidemia under the MS, we study the dynamics of some parameters of lipid and lipoprotein metabolism in hamsters of different sex and age. In our experiments, we found some age and gender differences in lipid and lipoprotein metabolism in healthy hamsters and hamsters with MS. In general, the obtained results demonstrate dyslipidemia development in males feeding high-calorie diet, irrespective of age. We suppose that hypertriglyceridemia in males under the high-calorie diet developed due to the accumulation of triacylglycerols T"Gs in hepatocytes and as a result very low density lipoprotein VLDL over secretion by liver. However, in females feeding high-calorie diet atherogenic dyslipoproteinemia develops only with aging. It can be assumed that the reason why high-calorie diet in females leads to the pathological changes in VLDL morphology and hypertriglyceridemia development is reducing the hepatocytes sensitivity to insulin. Herewith, insulin resistance in females does not cause lipolysis activation in adipose tissue, which is probably associated with the ability of female
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