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We studied the expression of genes encoding enzymes of carbohydrate and lipid metabolism ketohexokinase (Khk), glucokinase (Gck), pyruvate kinase (Pklr), acetyl-Co-carboxylase (Acaca), fatty acid synthase (Fasn), stearoyl-CoA desaturase (Scd), and their transcription regulators ChREBP (Mlxipl), SREBP-1c (Srebf1), and PPARα (Ppara) in rat liver. Control group rats received a semisynthetic ration over 20 weeks. Experimental group 1 received a semisynthetic ration and 20% fructose solution instead of drinking water. Experimental group 2 rats received a semisynthetic ration with quercetin (0.1% fodder weight) and 20% fructose solution. Consumption of 20% fructose solution (experimental group 1) led to an increase in Scd expression in comparison with the control and did not affect the expression of other genes. Addition of quercetin to the ration (experimental group 2) led to a decrease in the expression of Khk, Gck, Fasn, Scd, Mlxipl, and Ppara genes in comparison with experimental group 1. The results suggest that quercetin reduced the expression of genes of carbohydrate and lipid metabolism enzymes in the liver of rats receiving high-fructose ration. [ABSTRACT FROM AUTHOR]

Specialized products and dietary supplements, enriched with complexes of minor biologically active substances (BAS), are often offered as components of therapeutic diets in the treatment of obesity and metabolic syndrome. At the same time, the possible effects of the interactions of BAS when consuming a multicomponent product have not been studied enough. The aim - to study the action on rats' organism of a complex supplement (RС), containing resveratrol (Res) and L-carnitine (L-Car), when consumed with a standard balanced or hypercaloric diet. Material and methods . Male Wistar rats received for 63 days a standard balanced diet (SD) or a high-fat-high-carbohydrate diet (HFCD) with an excess of total fat (30%) and fructose (20% solution instead of drinking water), or the same diets supplemented with RС in a low (25 mg/kg body weight as Res and 300 mg/kg body weight as L-Car) or high (50 and 600 mg/kg body weight, respectively) doses. The muscle grip strength, behavioral reactions in tests of the conditioned passive avoidance reflex (CPAR) and elevated plus maze (EPM) were studied. At the end of the experiment, the mass of adipose tissue and internal organs was determined together with the activity of microsomal and cytosolic liver enzymes for specific substrates, plasma biochemical parameters, liver morphology by lightoptical microscopy, accumulation of lipofuscin-like granules (LLG) in the liver and kidneys by laser confocal microscopy. Results . In the rats fed HFCD, compared with SD, there was an increase in the mass index of liver, total inguinal and retroperitoneal white adipose tissue, in the levels of glucose and triglycerides, in the activity of hepatic CYP1A1 and CYP3A monooxygenases, UDPglucuronosyltransferase, heme oxygenase, and simultaneous decrease of high and low density lipoprotein cholesterol, and quinone oxidoreductase activity. The RС intake stimulated the locomotor activity of rats in EPM, however, this effect was less pronounced against the background of HFCD consumption. In rats consuming SD (but not HFCD), the addition of RС caused an increase in search activity and anxiety according to the EPM and CPAR data. The effect on short- and long-term memory retention was statistically insignificant. RС intake did not have hypolipidemic and hypoglycemic properties but caused in low dose an increase in the ratio of the activity of transaminases AST/ALT in animals fed HFCD. The liver CYP3A activity increased in rats supplemented with RС in high dose fed HFCD. In the kidneys of animals, the consumption of RС resulted in increased accumulation of LLG. Conclusion . When studying the effect of the complex supplement RС on normal and obese rats according to the studied physiological, morphological and biochemical indexes, no positive effects were revealed, that would not have manifested themselves for Res and L-Car separate intake. No evidence of synergistic action of L-Car and Res were found, and some of the effects of the complex supplement can be considered as adverse. This requires careful assessment when combined using these substances in complex diet therapy of metabolic disorders in humans., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

The use of nutraceuticals with anti-inflammatory and hypolipidemic activity in the composition of foods for special dietary uses and dietary supplements is one of the effective methods of dietary therapy of alimentary obesity and related diseases. The aim was to study the effect of the combined intake of resveratrol and L-carnitine (RC) on the expression of genes responsible for the metabolism of carbohydrates, fats and inflammatory reactions in the liver and kidneys of rats in normal conditions and with diet-induced obesity. Material and methods . Male Wistar rats received for 63 days a standard balanced diet or a high-fat-high-carbohydrate diet (HFCD) with an excess of total fat (30%) and fructose (20% solution instead of drinking water), or the same diets supplemented with RC in a low (25 mg/kg body weight as resveratrol and 300 mg/kg as L-carnitine) or high (50 and 600 mg/kg body weight, respectively) doses. The expression of genes (Khk, Gck, Pklr, Acaca, Acacb, Fasn, Scd, Srebf1, Mlxipl, Ppara, Pparg, Actb, Gapdh) in liver cells was studied by the method of real-time reverse transcription polymerase chain reaction (RT-PCR). The distribution of tyrosine aminotransferase (TAT), nuclear factor erythroid 2-related factor 2 (NRF-2) and intercellular adhesion molecule type 2 (ICAM-2) in the liver and kidneys was assessed by confocal laser microscopy and immunohistochemistry. Results . Increased expression of Fasn (fatty acid synthase) in rats treated with high-fat high-carbohydrate diet (HFCD) decreased under RC intake. RC consumption caused a decrease in the number of TAT-, NRF-2- and ICAM-2-positive cells in the liver of rats treated with HFCD, but had the opposite effect in the kidneys. The consumption of RC at the low dose by rats fed HFCD caused changes in the expression profiles of the studied marker genes, indicating a possible hypolipidemic effect. However, observed increased expression of lipogenic genes in the liver and elevated level of NRF-2 and ICAM-2 in kidney against the background of consumption of RC with the standard balanced diet cannot be assessed as unambiguously positive. Conclusion . Thus, possible negative effects caused, most likely, by the interaction of nutraceuticals with various mechanisms of action should be taken into account when developing formulations of dietary supplements and foods for special dietary uses for dietary therapy of obesity., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

Quercetin (Q; 3,3',4',5,7-pentahydroxyflavone) is considered as a promising component of specialized products for the correction of metabolic disorders in obesity and metabolic syndrome. At the same time, the results of evaluating the clinical efficacy of Q are ambiguous, and the mechanisms of its influence on lipid and carbohydrate-energy metabolism are not well understood. The aim of the work was to study the effect of quercetin (Q 3,3',4',5,7-pentahydroxyflavone) on the expression of key glycolysis and lipogenesis enzymes' genes in Zucker-Leprfa (Z) rats characterized by hereditary obesity, compared to «wild-type» Wistar (W) rats. Material and methods . 24 male Z rats and 32 male W rats aged 8-10 weeks were used. Animals of each line were divided into 4 groups of equal numbers. For 62 days the animals of the first groups (controls) received a balanced diet according to AIN93M, the seconds - the same diet with Q added in a dose of 50 mg/kg body weight. Animals of the third groups received a high-fat, high-carbohydrate diet (HFCD) with fat 30% by weight and with the replacement of drinking water with a 20% solution of fructose, the fourths groups - the same diet and supplementation with Q. After removing animals from the experiment, expression levels of liver carbohydrate and lipid metabolism genes Khk, Gck, Pklr, Acaca, Fasn, Scd, Srebf1, Mlxipl, Ppara and Pparg were determined by real-time polymerase chain reaction (RT-PCR) with reverse transcription using Actb and Gapdh as reference genes. The levels of triglycerides, total and HDL cholesterol, lipolytic activity and immunoreactive leptin were determined in plasma. Results and discussion . When comparing two animal lines, a significantly higher level of expression of Ppara, Pparg, Mlxipl, Acaca, Fasn, Scd was shown in Z rats compared to W rats, which is consistent with the development of dyslipidemia in the first ones and elevated levels of leptin under both types of diets used. The addition of Q caused in W rats a decrease in the expression of Scd, Mlxipl, Khk and Gck, more pronounced on the background of HFCD whereas in Z rats there were no similar effects, or they had the opposite direction. In addition, in Z rats, consumption of Q led to increased expression of Pklr, which was not observed in W rats. Conclusion . The modulating effect of Q on the expression of key genes of lipid and carbohydrate metabolism enzymes significantly differs in wild-type W rats and mutant Z rats with hereditary obesity, and this difference appears to be potentiated by the consumption of excess fat and fructose., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

Biochemical, vitamin, trace element and immunological changes were searched for the combined nutritional deficiency of vitamins B1, B2, B6 on in vivo models in rats and mice. Female rats of Wistar (W) strain and hybrids of the 1st generation of Dark Aguti and Wistar (DA x W) strains, female mice of BALB/c strain and DBCB tetrahybrids were used in experiment. Animals received for 35 days a balanced diet (control) according to AIN-93 or a similar diet with the exception of vitamins B1, B2, B6 (experimental groups). The content of vitamins B1, B2 in liver, riboflavin blood plasma level and urinary excretion of thiamine, riboflavin and 4-pyridoxic acid were determined, as well as in rats: blood and liver content of α-tocopherol and retinol, blood biochemical indices of lipid and nitrogen metabolism, activity of cytochrome P isoforms-450 (CYP) in liver; in mice: the circulating levels of pro- and anti-inflammatory cytokines of blood plasma, in animals of both species - the content of essential and toxic elements in the kidneys. DAxW rats compared to W and DBCB mice compared to BALB/c were more sensitive to the development of B-vitamin deficiency judging by the B-vitamin status indicators. In the rats of the experimental groups, there were signs of a deterioration in blood and liver levels of vitamin E, multidirectional shifts in vitamin A sufficiency, increased activity of the CYP3A isoform (6β-TG), a decrease in triglycerides, total protein and albumin fraction levels with an increase in urea level. Manifestation degree of these effects depended on the choice of the animal's line. In mice, the B-vitamin deficiency was characterized by an increase in the levels of proinflammatory cytokines TNF-α, IL-10, IL-Ιβ, IL-6 and a decrease in IFN-γ and IL-17A. The content of magnesium, copper, zinc, chromium and silver was lowered, of cesium - was increased in the kidneys of the rats of the experimental groups. In mice, B-vitamin deficiency resulted in diminishment of magnesium, copper, zinc, chromium, selenium, cadmium and lead content, excess accumulation of cobalt and cesium. Some of these biomarkers are supposed to be used in pre-clinical evaluation of the effectiveness of new vitamin complexes, specialized foods and dietary supplements, as well as studies of interactions of various vitamins., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

The purpose of the study was to determine effects of quercetin on protective capacity parameters in the experiment on rats fed a high fructose diet. Rats of the control group received a semi-synthetic (s/s) diet and water; animals from the 1st experimental group - s/s diet and 20% fructose solution instead of drinking water; rats of the 2nd experimental group- s/s diet with quercetin (0.1% indiet) and 20% fructose solution instead of drinking water for 20 weeks. Parameters of antioxidant status [total antioxidant activity (AOA), the content of malondialdehyde (MDA) and lipids hydroperoxides, the level of reduced and oxidized glutathione, activity of superoxide dismutase, catalase, glutathione peroxidase, paraoxonase-1, hemeoxygenase-1, NAD(P)H-quinone oxidoreductase], the activity of xenobiotic-metabolizing enzymes [CYP1A1, CYP1A2, CYP2B1, CYP3A, UDP-glucuronosyltransferase (UDP-GT) and glutathione transferase] were studied in plasma and liver of rats. Consumption of the high-fructose diet led to changes in some parameters: diminution of AOA in blood plasma, decrease of AOA and MDA level, unsedimentable activity of lysosomal enzymes, increase of the UDP-GT activity in liver. The inclusion of quercetin in the diet did not affect the studied parameters, except for a more pronounced decrease of the unsedimentable activity of lysosomal enzymes in rat liver. The results of the study indicated that there was no significant effect of quercetin on the protective capacity of rats at the initial stage of obesity caused by high-fructose diet., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

The purpose of the study was to determine the effects of curcumin (CUR) and quercetin (QUER) on the expression of genes and activity of prototypical Nrf2/ARE- and AhR/ XRE-regulated enzymes. Investigation was carried out on male Wistar rats with initial body weight (230-235 g b.w.) that received for 14 days CUR (200 mg/kg b.w.) and QUER (200 mg/kg b.w.) separately or in combination within the standard semi-synthetic diet. The expression of genes and activity of Nrf2/ARE - regulated enzymes - heme oxygenase- 1(HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), AhR/XRE-regulated CYP1A1, CYP1A2 enzymes and the mRNA level of transcription factors Nrf2 and AhR were determined in rats liver. Also the expression of gene CYP3A1 and activity of CYP3A, UDP-glucuronosyltransferase, glutathione transferase were studied in rats liver. Along with this the total antioxidant activity (AOA), malondialdehyde and lipid hydroperoxides levels were determined in blood plasma and liver. The reduced and oxidized glutathione level, total and unsedimentable activity of lysosomal enzymes were investigated in rats' liver. QUER, especially in combination with CUR, increased the AOA of blood plasma and reduced the content of lipid hydroperoxides in it. CUR and QUER did not affect NQO1 activity, but the combined action caused an increase in the HO-1 activity without affecting the expression of the corresponding gene (Hmox1) and Nrf2 gene. CUR and, to a lesser extent QUER, had a strong inducing effect on CYP1A1, CYP1A2, CYP3A activity, but only the CYP1A1 activation was accompanied by the induction of CYP1A1 gene. The inducing effect of CUR and QUER on the activity of CYP450 enzymes greatly enhanced by their combined action. Membrane stabilizing action of CUR and QUER was also strongly expressed under its combined intake. Thus, we can conclude that CUR and QUER, especially in combination, contribute to the protective and adaptive capacity., (Copyright© GEOTAR-Media Publishing Group.)