Hypolipidemic and cardioprotective effects of statins can be associated with the development of myopathies and new-onset type 2 diabetes. These adverse effects may be related to increased oxidative stress. The plant extract silymarin (SM) is known for its antioxidant and anti-inflammatory actions. We tested the hypothesis that the combination of atorvastatin (ATV) with SM could improve therapy efficacy and eliminate some negative effects of statin on hypertriglyceridemia-induced metabolic disorders. Hereditary hypertriglyceridemic rats were fed a standard diet for four weeks without supplementation; supplemented with ATV (5 mg/kg b. wt./day) or a combination of ATV with 1 % micronized SM (ATV+SM). ATV treatment elevated plasma levels of HDL-cholesterol (p<0.01), glucose and insulin and decreased triglycerides (p<0.001). The combination of ATV+SM led to a significant reduction in insulin, an improvement of glucose tolerance, and the hypolipidemic effect was enhanced compared to ATV alone. Furthermore, ATV supplementation increased skeletal muscle triglycerides but its combination with SM decreased triglycerides accumulation in the muscle (p<0.05) and the liver (p<0.01). In the liver, ATV+SM treatment increased the activities of antioxidant enzymes, glutathione and reduced lipid peroxidation (p<0.001). The combined administration of ATV with SM potentiated the hypolipidemic effect, reduced ectopic lipid accumulation, improved glucose metabolism, and increased antioxidant and anti-inflammatory actions. Our results show that SM increased the effectiveness of statin therapy in a hypertriglyceridemic rat model of metabolic syndrome.
- MeSH
- anticholesteremika škodlivé účinky MeSH
- antioxidancia farmakologie MeSH
- atorvastatin škodlivé účinky MeSH
- diabetes mellitus 2. typu chemicky indukované farmakoterapie patologie MeSH
- hypercholesterolemie krev MeSH
- hyperlipidemie farmakoterapie MeSH
- kombinovaná farmakoterapie MeSH
- krysa rodu Rattus MeSH
- metabolický syndrom farmakoterapie genetika patologie MeSH
- modely nemocí na zvířatech MeSH
- oxidační stres účinky léků MeSH
- silymarin farmakologie MeSH
- triglyceridy krev MeSH
- zánět farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- anticholesteremika MeSH
- antioxidancia MeSH
- atorvastatin MeSH
- silymarin MeSH
- triglyceridy MeSH
Membrane endoglin (Eng, CD105) is a transmembrane glycoprotein essential for the proper function of vascular endothelium. It might be cleaved by matrix metalloproteinases to form soluble endoglin (sEng), which is released into the circulation. Metabolic syndrome comprises conditions/symptoms that usually coincide (endothelial dysfunction, arterial hypertension, hyperglycemia, obesity-related insulin resistance, and hypercholesterolemia), and are considered risk factors for cardiometabolic disorders such as atherosclerosis, type II diabetes mellitus, and liver disorders. The purpose of this review is to highlight current knowledge about the role of Eng and sEng in the disorders mentioned above, in vivo and in vitro extent, where we can find a wide range of contradictory results. We propose that reduced Eng expression is a hallmark of endothelial dysfunction development in chronic pathologies related to metabolic syndrome. Eng expression is also essential for leukocyte transmigration and acute inflammation, suggesting that Eng is crucial for the regulation of endothelial function during the acute phase of vascular defense reaction to harmful conditions. sEng was shown to be a circulating biomarker of preeclampsia, and we propose that it might be a biomarker of metabolic syndrome-related symptoms and pathologies, including hypercholesterolemia, hyperglycemia, arterial hypertension, and diabetes mellitus as well, despite the fact that some contradictory findings have been reported. Besides, sEng can participate in the development of endothelial dysfunction and promote the development of arterial hypertension, suggesting that high levels of sEng promote metabolic syndrome symptoms and complications. Therefore, we suggest that the treatment of metabolic syndrome should take into account the importance of Eng in the endothelial function and levels of sEng as a biomarker and risk factor of related pathologies.
- Klíčová slova
- Endoglin, Endothelial dysfunction, Hyperglycemia, Metabolic syndrome, Soluble endoglin,
- MeSH
- ateroskleróza metabolismus patologie MeSH
- biologické markery metabolismus MeSH
- buněčná membrána metabolismus MeSH
- diabetes mellitus 2. typu metabolismus patologie MeSH
- endoglin chemie metabolismus MeSH
- exprese genu MeSH
- kardiovaskulární nemoci metabolismus patologie MeSH
- lidé MeSH
- metabolický syndrom metabolismus patologie MeSH
- synthasa oxidu dusnatého, typ III metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
- endoglin MeSH
- synthasa oxidu dusnatého, typ III MeSH
BACKGROUND: Psoriasis is a pathological condition characterized by immune system dysfunction and inflammation. Patients with psoriasis are more likely to develop a wide range of disorders associated with inflammation. Serum levels of various substances and their combinations have been associated with the presence of the disease (psoriasis) and have shown the potential to reflect its activity. The aim of the present study is to contribute to the elucidation of pathophysiological links between psoriasis, its pro-inflammatory comorbidity metabolic syndrome (MetS), and the expression of clusterin and elafin, which are reflected in the pathophysiological "portfolio" of both diseases. MATERIAL AND METHODS: Clinical examinations (PASI score), ELISA (clusterin, elafin), and biochemical analyses (parameters of MetS) were performed. RESULTS: We found that patients with psoriasis were more often afflicted by MetS, compared to the healthy controls. Clusterin and elafin levels were higher in the patients than in the controls but did not correlate to the severity of psoriasis. CONCLUSION: Our data suggest that patients with psoriasis are more susceptible to developing other systemic inflammatory diseases, such as MetS. The levels of clusterin and elafin, which are tightly linked to inflammation, were significantly increased in the patients, compared to the controls, but the presence of MetS in patients did not further increase these levels.
- Klíčová slova
- clusterin, elafin, metabolic syndrome, psoriasis,
- MeSH
- dospělí MeSH
- elafin genetika MeSH
- index tělesné hmotnosti MeSH
- klusterin genetika MeSH
- komorbidita MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom komplikace genetika metabolismus patologie MeSH
- psoriáza komplikace genetika metabolismus patologie MeSH
- regulace genové exprese genetika MeSH
- studie případů a kontrol MeSH
- stupeň závažnosti nemoci MeSH
- zánět genetika metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- CLU protein, human MeSH Prohlížeč
- elafin MeSH
- klusterin MeSH
- PI3 protein, human MeSH Prohlížeč
Both prenatal and postnatal excessive consumption of dietary sucrose or fructose was shown to be detrimental to health and contributing to pathogenesis of metabolic syndrome. Our knowledge of genetic determinants of individual sensitivity to sucrose-driven metabolic effects is limited. In this study, we have tested the hypothesis that a variation of metabolic syndrome-related gene, Zbtb16 (Zinc Finger and BTB Domain Containing 16 will affect the reaction to high-sucrose diet (HSD) content in "matched" nutritional exposition settings, i.e. maternal HSD with re-exposition to HSD in adulthood vs. standard diet. We compared metabolic profiles of adult males of spontaneously hypertensive rats (SHR) and a single-gene, minimal congenic strain SHR-Zbtb16 fed either standard diet or exposed to HSD prenatally throughout gestation and nursing and again at the age of 6 months for the period of 14 days. HSD exposition led to increased adiposity in both strains and decrease of glucose tolerance and cholesterol (Ch) concentrations in majority of low-density lipoprotein (LDL) particle classes and in very large and large high-density lipoprotein (HDL) in SHR-Zbtb16 male offspring. There was a similar pattern of HSD-induced increase of triacylglycerols in chylomicrons and very low-density lipoprotein (VLDL) of both strains, though the increase of (triacylglycerol) TAG content was clearly more pronounced in SHR. We observed significant STRAIN*DIET interactions for the smallest LDL particles as their TAG content decreased in SHR-Zbtb16 and did not change in SHR in response to HSD. In summary, we provide evidence of nutrigenetic interaction between Zbtb16 and HSD in context of pathogenesis of metabolic syndrome.
- MeSH
- cholesterol metabolismus MeSH
- hypertenze genetika metabolismus MeSH
- konzumní sacharóza metabolismus MeSH
- krysa rodu Rattus MeSH
- metabolický syndrom etiologie metabolismus patologie MeSH
- modely nemocí na zvířatech MeSH
- nutrigenomika metody MeSH
- potkani inbrední SHR MeSH
- protein promyelocytické leukemie s motivem zinkového prstu genetika metabolismus MeSH
- sladidla metabolismus MeSH
- těhotenství MeSH
- triglyceridy metabolismus MeSH
- zvířata kongenní MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cholesterol MeSH
- konzumní sacharóza MeSH
- protein promyelocytické leukemie s motivem zinkového prstu MeSH
- sladidla MeSH
- triglyceridy MeSH
- ZBTB16 protein, rat MeSH Prohlížeč
In this study, we investigated the influence of metformin (MF) on proliferation and viability of adipose-derived stromal cells isolated from horses (EqASCs). We determined the effect of metformin on cell metabolism in terms of mitochondrial metabolism and oxidative status. Our purpose was to evaluate the metformin effect on cells derived from healthy horses (EqASCHE) and individuals affected by equine metabolic syndrome (EqASCEMS). The cells were treated with 0.5 μM MF for 72 h. The proliferative activity was evaluated based on the measurement of BrdU incorporation during DNA synthesis, as well as population doubling time rate (PDT) and distribution of EqASCs in the cell cycle. The influence of metformin on EqASC viability was determined in relation to apoptosis profile, mitochondrial membrane potential, oxidative stress markers and BAX/BCL-2 mRNA ratio. Further, we were interested in possibility of metformin affecting the Wnt3a signalling pathway and, thus, we determined mRNA and protein level of WNT3A and β-catenin. Finally, using a two-tailed RT-qPCR method, we investigated the expression of miR-16-5p, miR-21-5p, miR-29a-3p, miR-140-3p and miR-145-5p. Obtained results indicate pro-proliferative and anti-apoptotic effects of metformin on EqASCs. In this study, MF significantly improved proliferation of EqASCs, which manifested in increased synthesis of DNA and lowered PDT value. Additionally, metformin improved metabolism and viability of cells, which correlated with higher mitochondrial membrane potential, reduced apoptosis and increased WNT3A/β-catenin expression. Metformin modulates the miRNA expression differently in EqASCHE and EqASCEMS. Metformin may be used as a preconditioning agent which stimulates proliferative activity and viability of EqASCs.
- Klíčová slova
- adipose-derived stromal cells, equine metabolic syndrome, metformin,
- MeSH
- apoptóza účinky léků MeSH
- beta-katenin metabolismus MeSH
- buněčný cyklus účinky léků MeSH
- koně MeSH
- kultivované buňky MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- metabolický syndrom farmakoterapie patologie veterinární MeSH
- metformin farmakologie terapeutické užití MeSH
- mikro RNA genetika metabolismus MeSH
- mitochondrie účinky léků metabolismus MeSH
- multipotentní kmenové buňky cytologie MeSH
- oxidace-redukce MeSH
- proliferace buněk účinky léků MeSH
- protein Wnt3A metabolismus MeSH
- separace buněk * MeSH
- tuková tkáň cytologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- beta-katenin MeSH
- metformin MeSH
- mikro RNA MeSH
- protein Wnt3A MeSH
Chronic low-grade inflammation plays an important role in the pathogenesis of insulin resistance. In the current study, we tested the effects of salsalate, a non-steroidal anti-inflammatory drug, in an animal model of inflammation and metabolic syndrome using spontaneously hypertensive rats (SHR) that transgenically express human C-reactive protein (SHR-CRP rats). We treated 15-month-old male transgenic SHR-CRP rats and nontransgenic SHR with salsalate (200 mg/kg/day) mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP and SHR rats were fed a standard diet without salsalate. In the SHR-CRP transgenic strain, salsalate treatment decreased circulating concentrations of the inflammatory markers TNF-α and MCP-1, reduced oxidative stress in the liver and kidney, increased sensitivity of skeletal muscles to insulin action and improved tolerance to glucose. In SHR controls with no CRP-induced inflammation, salsalate treatment reduced body weight, decreased concentrations of serum free fatty acids and total and HDL cholesterol and increased palmitate oxidation and incorporation in brown adipose tissue. Salsalate regulated inflammation by affecting the expression of genes from MAPK signalling and NOD-like receptor signalling pathways and lipid metabolism by affecting hepatic expression of genes that favour lipid oxidation from PPAR-α signalling pathways. These findings suggest that salsalate has metabolic effects beyond suppressing inflammation.
- MeSH
- C-reaktivní protein biosyntéza genetika MeSH
- geneticky modifikovaná zvířata genetika MeSH
- hnědá tuková tkáň metabolismus MeSH
- hypertenze farmakoterapie genetika patologie MeSH
- inzulinová rezistence genetika MeSH
- játra metabolismus MeSH
- krysa rodu Rattus MeSH
- kyseliny mastné neesterifikované metabolismus MeSH
- lidé MeSH
- metabolický syndrom farmakoterapie genetika patologie MeSH
- metabolismus lipidů účinky léků MeSH
- NLR proteiny biosyntéza MeSH
- oxidační stres účinky léků MeSH
- PPAR alfa biosyntéza MeSH
- salicylany aplikace a dávkování MeSH
- TNF-alfa biosyntéza MeSH
- zánět farmakoterapie genetika patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- C-reaktivní protein MeSH
- kyseliny mastné neesterifikované MeSH
- NLR proteiny MeSH
- PPAR alfa MeSH
- salicylany MeSH
- salicylsalicylic acid MeSH Prohlížeč
- TNF-alfa MeSH
The presented article studies the role of selected inflammatory and anti-inflammatory serum markers of psoriatic patients in the pathogenesis of metabolic syndrome (MS) and psoriasis. The study is based on the comparison between the group of psoriatic patients (74) and the control group (65). We found significantly higher BMI (p < 0.05) and diastolic blood pressure (p < 0.05) in the psoriatic patients. The values of waist circumference and BMI were significantly higher (p < 0.05) in the male patients compared to the men in the control group. The analysis revealed significantly higher CRP (p < 0.001), Lp-PLA2 (p < 0.001), leptin (p < 0.01), and resistin (p < 0.01) levels in the psoriatic patients. Significantly higher levels of CRP (p < 0.01), Lp-PLA2 (p < 0.001), leptin (p < 0.01), and resistin (p < 0.05) were found in the patients with MS compared to the controls with MS. The level of adiponectin was significantly lower (p < 0.01) in the patients with MS. Finally, we found significantly higher level of Lp-PLA2 (p < 0.001) in the group of patients without MS compared to the controls without MS. In conclusion, observed inflammatory and anti-inflammatory markers (CRP, adiponectin, leptin, resistin, and Lp-PLA2) are involved in both pathogenesis of MS and pathogenesis of psoriasis. The level of Lp-PLA2 indicates the presence of subclinical atherosclerosis (cardiovascular risk) in psoriatic patients.
- MeSH
- 1-alkyl-2-acetylglycerofosfocholinesterasa krev MeSH
- adiponektin krev MeSH
- biologické markery krev MeSH
- C-reaktivní protein metabolismus MeSH
- dospělí MeSH
- index tělesné hmotnosti MeSH
- krevní tlak MeSH
- leptin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom krev imunologie patologie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- obvod pasu MeSH
- psoriáza krev imunologie patologie MeSH
- resistin krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 1-alkyl-2-acetylglycerofosfocholinesterasa MeSH
- adiponektin MeSH
- biologické markery MeSH
- C-reaktivní protein MeSH
- leptin MeSH
- resistin MeSH
Numerous chemicals in the environment have the ability to interact with the endocrine system. These compounds are called endocrine disruptors (EDs). Exposure to EDs represents one of the hypotheses for decreasing fertility, the increased risk of numerous cancers and obesity, metabolic syndrome and type 2 diabetes. There are various mechanisms of ED action, one of which is their interference in the action of 11β-hydroxysteroid dehydrogenase (11βHSD) that maintains a balance between active and inactive glucocorticoids on the intracellular level. This enzyme has two isoforms and is expressed in various tissues. Inhibition of 11βHSD in various tissues can have different consequences. In the case of EDs, the results of exposure are mainly adverse; on the other hand pharmaceutically developed inhibitors of 11βHSD type 1 are evaluated as an option for treating metabolic syndrome, as well as related diseases and depressive disorders. This review focuses on the effects of 11βHSD inhibitors in the testis, colon, adipose tissue, kidney, brain and placenta.
- Klíčová slova
- 11β-hydroxysteroid dehydrogenase, Adipose tissue, Brain, Colon, Endocrine disruptor, Inhibitor, Placenta, Testis,
- MeSH
- 11-beta-hydroxysteroiddehydrogenasa typ 1 antagonisté a inhibitory metabolismus MeSH
- 11-beta-hydroxysteroiddehydrogenasa typ 2 antagonisté a inhibitory metabolismus MeSH
- diabetes mellitus chemicky indukované enzymologie patologie MeSH
- endokrinní disruptory farmakologie MeSH
- glukokortikoidy metabolismus MeSH
- inhibitory enzymů farmakologie MeSH
- kolon účinky léků enzymologie MeSH
- lidé MeSH
- metabolický syndrom chemicky indukované enzymologie patologie MeSH
- mozek účinky léků enzymologie MeSH
- nádory chemicky indukované enzymologie patologie MeSH
- obezita chemicky indukované enzymologie patologie MeSH
- orgánová specificita MeSH
- placenta účinky léků enzymologie MeSH
- těhotenství MeSH
- testis účinky léků enzymologie MeSH
- tuková tkáň účinky léků enzymologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
- 11-beta-hydroxysteroiddehydrogenasa typ 2 MeSH
- endokrinní disruptory MeSH
- glukokortikoidy MeSH
- inhibitory enzymů MeSH
OBJECTIVE: Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals. METHODS: The cohort consisted of 589 healthy subjects aged 18-65 years. We studied the associations between the serum uric acid concentration and the following: (i) demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii) the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii) selected genetic variants of the MTHFR (c.665C>T, c.1286A>C), SLC2A9 (c.844G>A, c.881G>A) and ABCG2 genes (c.421C>A). A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables. RESULTS: The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations. CONCLUSION: Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.
- MeSH
- ABC transportér z rodiny G, člen 2 MeSH
- ABC transportéry krev genetika MeSH
- dospělí MeSH
- exprese genu MeSH
- jednonukleotidový polymorfismus * MeSH
- kohortové studie MeSH
- kyselina močová krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom krev genetika patologie MeSH
- methylentetrahydrofolátreduktasa (NADPH2) krev genetika MeSH
- mladiství MeSH
- modely genetické MeSH
- nádorové proteiny krev genetika MeSH
- pití alkoholu krev genetika patologie MeSH
- proteiny usnadňující transport glukosy krev genetika MeSH
- regresní analýza MeSH
- senioři MeSH
- sexuální faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABC transportér z rodiny G, člen 2 MeSH
- ABC transportéry MeSH
- ABCG2 protein, human MeSH Prohlížeč
- kyselina močová MeSH
- methylentetrahydrofolátreduktasa (NADPH2) MeSH
- MTHFR protein, human MeSH Prohlížeč
- nádorové proteiny MeSH
- proteiny usnadňující transport glukosy MeSH
- SLC2A9 protein, human MeSH Prohlížeč
