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1.
Molecules ; 24(17)2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31450672

RESUMO

Morus alba L. (white mulberry) has been commonly used as a functional food and for medicinal purposes. Hence, the aim of the study was to compare the phenolic profile of white mulberry commercial samples in relation to their antioxidant potential and acetylcholinesterase (AChE) inhibitory activity. It is of interest to determine whether herbal products originating from different commercial sources differ in their phenolic profiles. For this purpose, a simple and rapid high-performance liquid chromatography (HPLC) method was used for the separation and determination of ten major phenolic compounds. Total phenolic (TPC), total flavonoid (TFC), and total phenolic acid contents (TPAC), as well as l(+)-ascorbic acid (ASA) contents, were determined. The antioxidant potential was assessed by DPPH (2,2-diphenyl-1-picrylhydrazyl radical) scavenging activity and ferric-reducing/antioxidant power (FRAP) assay, while the AChE inhibitory activity was determined by the Ellman assay for water extracts. The study revealed that excluding two herbal products containing fruits and a sample containing leaves of white mulberry, yerba mate and lemon, the remaining samples were generally consistent in terms of phenolic composition as well as antioxidant potential and AChE inhibitory activity. This reflects the health-promoting properties of the samples under study. Moreover, the results showed that the water extracts of white mulberry were richer in phenolic compounds and presented higher antioxidant activity than the hydromethanolic extracts. However, the water extracts showed low inhibitory activity against AChE. Moreover, the correlation analysis indicated a high positive relationship between phenolic composition and antioxidant activity in extracts of white mulberry. Overall, the obtained results may be useful in the evaluation of new dietary supplements and food products. The water extracts of white mulberry could be used for antioxidant purposes, while the hydromethanolic extracts could be incorporated in antioxidant formulations.


Assuntos
Morus/química , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Ácido Ascórbico/química , Cromatografia Líquida de Alta Pressão , Flavonoides , Hidroxibenzoatos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia
2.
Gerontology ; 61(5): 448-55, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25721559

RESUMO

BACKGROUND: Although the heterogeneity of white adipose tissue (WAT) in different anatomical sites is a well-known phenomenon, there are scarce data on aging-associated metabolic alterations in various WAT depots. OBJECTIVE: We used the model of fasting and refeeding to analyze the effect of aging on the activity of key lipogenic enzymes in retroperitoneal (rWAT), epididymal (eWAT), and subcutaneous (sWAT) adipose tissue depots. METHODS: 5- and 24-month-old male Wistar rats were fasted for 48 h or were fasted for 2 days and subsequently refed for 2 or 4 days. Control animals had ad libitum access to chow. Samples obtained from three WAT deposits were analyzed for the enzymatic activities of ATP citrate lyase (ACL), fatty acid synthase (FAS), and glucose-6-phosphate dehydrogenase (G6PD). Concentrations of lipids and proteins were measured in the blood serum. RESULTS: Fasting for 2 days decreased the concentration of free fatty acids only in the young rats. The basal activities of ACL and FAS were lower in eWAT than in rWAT and sWAT of the young rats. In the young rats, fasting did not change ACL and FAS activities in any of the studied depots. Refeeding increased these activities more quickly in rWAT than in eWAT, while in sWAT no induction was observed. ACL and FAS activities were manifold lower in all WAT depots of the old than in those of the young rats. In the old animals fasting had no effect on ACL activity in any depot and decreased FAS activity only in sWAT. After 4 days of refeeding, FAS activity increased in rWAT and sWAT, but no change in ACL activity occurred. G6PD activity in the young rats was lower by 40% in eWAT than in rWAT. The induction of the enzyme by refeeding occurred faster in rWAT than in eWAT, while in sWAT no change in G6PD activity was observed. G6PD activity did not change with aging. Fasting of the old rats decreased G6PD activity in rWAT and sWAT. Refeeding failed to induce the enzyme in these depots, whereas in eWAT G6PD activity increased by 76% after 4 days of refeeding. CONCLUSION: Fasting and refeeding revealed WAT depot-specific, age-related changes of the activities of lipogenic enzymes.


Assuntos
Tecido Adiposo Branco/enzimologia , Envelhecimento/metabolismo , Lipogênese , ATP Citrato (pro-S)-Liase/metabolismo , Envelhecimento/sangue , Animais , Peso Corporal , Ingestão de Alimentos/fisiologia , Jejum/metabolismo , Ácido Graxo Sintase Tipo I/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Lipídeos/sangue , Masculino , Ratos , Ratos Wistar , Distribuição Tecidual
3.
Cell Physiol Biochem ; 34(4): 1101-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25228402

RESUMO

BACKGROUND/AIMS: The fatty acid profile in plasma lipids contributes to the increase of plasma high sensitivity C-reactive protein (hsCRP), a marker of inflammation and predictor of cardiovascular risk. The aim of this study was to examine the relationship between specific fatty acids (FA) of serum lipids and serum hsCRP in morbidly obese woman. METHODS: The study included 16 morbidly obese (mean BMI= 43 ± 2.2 kg/m(2)) non-diabetic woman awaiting bariatric surgery. FA extracted from serum lipids were methylated and analyzed on GC-MS. Commercially available ELISA kits were used to determine the serum inflammatory markers. RESULTS: We demonstrated that total saturated FA (SFA) and total monounsaturated FA (MUFA) of serum lipids were positively correlated with serum hsCRP, whereas both n-3 and n-6 total polyunsaturated FA (PUFA) were negatively correlated with serum hsCRP. Serum interleukin-6 correlated positively with some SFA and MUFA, whereas negatively with some of PUFA. Positive correlation between serum hsCRP and specific SFA and MUFA or negative correlation with PUFA decreased with the increased FA chain length. The number and localization of double bonds also had impact on these correlations. CONCLUSION: Our findings suggest that individual serum lipid FA levels, depending on the length of FA chain, number and the localization of double bonds are distinctly associated with hsCRP in morbidly obese subjects.


Assuntos
Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Ácidos Graxos/sangue , Lipídeos/sangue , Obesidade Mórbida/sangue , Obesidade Mórbida/metabolismo , Adulto , Ácidos Graxos Monoinsaturados/sangue , Ácidos Graxos Insaturados/sangue , Feminino , Humanos , Inflamação/sangue , Inflamação/metabolismo , Interleucina-6/sangue , Fatores de Risco
4.
Cell Physiol Biochem ; 32(2): 300-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23942261

RESUMO

BACKGROUND/AIMS: Cytosolic glycerol 3-phosphate dehydrogenase (cGPDH) is a key enzyme providing glycerol 3-phosphate for triacylglycerol synthesis in adipose tissue and is regarded as a marker for adipocyte differentiation. The aim of this study was to test the hypothesis that an increase in cGPDH gene expression in subcutaneous adipose tissue is associated with obesity. METHODS: mRNA levels in human subcutaneous adipose tissue were analysed by Real-Time PCR. RESULTS: We found that human subcutaneous adipose tissue cGPDH activity and cGPDH mRNA level were greater in obese patients than in lean subjects and were positively correlated with BMI and fat mass. Moreover, a strong positive correlation between subcutaneous adipose tissue cGPDH mRNA level and cGPDH activity was found. The data presented here indicates also that PPARγ mRNA level is positively correlated with body mass index and fat mass as well as with adipose tissue cGPDH mRNA level. Moreover, the association between subcutaneous adipose tissue cGPDH mRNA level and fatty acid translocase (FAT/CD36) mRNA level was also observed. CONCLUSION: The obtained results suggest that in comparison to lean subjects the increase in subcutaneous adipose tissue cGPDH gene expression in the obese, is probably the result of adipose tissue expansion during obesity.


Assuntos
Índice de Massa Corporal , Citosol/enzimologia , Regulação da Expressão Gênica , Glicerolfosfato Desidrogenase/genética , Glicerolfosfato Desidrogenase/metabolismo , Gordura Subcutânea/enzimologia , Adulto , Glicemia/análise , Feminino , Perfilação da Expressão Gênica , Glicerofosfatos/metabolismo , Humanos , Insulina/sangue , Insulina/química , Masculino , Pessoa de Meia-Idade , Obesidade/enzimologia
5.
Antioxidants (Basel) ; 12(3)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36978798

RESUMO

In the present study, the chemical composition and bioactive properties of commercially available Withania somnifera samples were evaluated. The hydromethanolic and aqueous extracts of the tested samples were analyzed in terms of phenolic compound composition, ascorbic acid content, antioxidant and antibacterial activity, and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Polyphenols and ascorbic acid content, as well as the antioxidant activity, were higher in the aqueous extracts than in the hydromethanolic extracts. Generally, aqueous extracts presented higher antioxidant activity than the hydromethanolic ones, especially in the case of 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. Moreover, higher amounts of phenolic acids and flavonoids were found in the hydromethanolic extracts compared to the aqueous ones. Regarding the antibacterial properties, samples 4, 6, and 10 showed the best overall performance with growth-inhibitory activities against all the examined bacteria strains. Finally, the aqueous and hydromethanolic extracts were the most efficient extracts in terms of AChE and BChE inhibitory activities, respectively. In conclusion, our results indicate that W. somnifera possesses important bioactive properties which could be attributed to the high amounts of phenolic compounds. However, a great variability was recorded in commercially available products, suggesting significant differences in the origin of product and the processing method.

6.
Pancreatology ; 11(4): 434-40, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21921666

RESUMO

BACKGROUND: In vitro studies suggest that platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-ß1 (TGF-ß1) play an important role in pancreatic fibrosis. The aim of this study was to evaluate serum PDGF-BB and TGF-ß1 concentrations in patients with chronic pancreatitis (CP). METHODS: Forty male patients with a history of alcoholic CP and 35 age-matched healthy subjects were examined. Serum concentrations of PDGF-BB, TGF-ß1, laminin and hyaluronic acid were determined by ELISA assay. Additionally, we determined serum concentrations of PDGF-BB and TGF-ß1 in patients with functional dyspepsia, ulcerative colitis and Crohn's disease. RESULTS: Patients with advanced CP had significantly higher serum PDGF-BB and TGF-ß1 concentrations compared to control subjects. A strong positive correlation between serum PDGF-BB and TGF-ß1 concentrations was found in patients with CP. Serum laminin and hyaluronic acid were also elevated in patients with CP. No increase in serum PDGF-BB and TGF-ß1 concentrations was found in patients with functional dyspepsia, ulcerative colitis or Crohn's disease. CONCLUSION: The obtained results indicate for the first time that serum levels of PDGF-BB are elevated in patients with CP. However, ROC curve analysis suggests that PDGF-BB is not superior to laminin as a potential marker of advanced CP.


Assuntos
Pancreatite Alcoólica/sangue , Proteínas Proto-Oncogênicas c-sis/sangue , Fator de Crescimento Transformador beta1/sangue , Adulto , Becaplermina , Biomarcadores/sangue , Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Dispepsia/sangue , Dispepsia/diagnóstico , Humanos , Laminina/sangue , Masculino , Pessoa de Meia-Idade , Pancreatite Alcoólica/diagnóstico
7.
Prz Gastroenterol ; 16(1): 56-61, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33986889

RESUMO

INTRODUCTION: Walled-off pancreatic necrosis (WOPN) is a life-threatening, late complication of acute pancreatitis, in which a fluid collection containing necrotic material is formed. Infection of the fluid collection significantly increases the mortality of patients with WOPN. AIM: To examine the levels of oxidative stress markers in the pancreatic necrotic fluid (PNF) and serum of patients with sterile and infected WOPN. MATERIAL AND METHODS: Thirty-three adult patients with sterile WOPN and 14 with infected WOPN, as well as 31 patients with mild AP, were included in this study. Concentrations of oxidative stress markers (8-isoprostane, protein carbonyl groups, and 8-hydroxyguanine) were measured in the PNF and serum of patients with sterile and infected WOPN. RESULTS: High concentrations of all measured oxidative stress markers in PNF, but not in serum, were detected in patients with WOPN. Additionally, oxidative stress markers in PNF were significantly increased in patients with infected as compared to sterile WOPN. The serum high sensitive C-reactive protein (hsCRP) concentrations showed the highest correlation with PNF oxidative stress marker levels. Receiver operating characteristics (ROC) curve analysis confirmed that serum hsCRP could be a good predictor of WOPN infection. CONCLUSIONS: Oxidative stress is associated with WOPN development; infection of PNF worsens the course of WOPN, possibly via increased production of reactive oxygen species; and serum hsCRP concentrations seem to be a good, noninvasive indicator of PNF infection.

8.
J Clin Gastroenterol ; 43(1): 63-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18827713

RESUMO

BACKGROUND: Resistin is an adipokine, which displays proinflammatory properties. Thus, it is likely that resistin can influence the course of chronic pancreatitis, and/or that chronic pancreatitis may affect the serum resistin concentration. GOALS: The aim of the present study was to determine the serum resistin concentration in patients with chronic pancreatitis and to analyze the relationship between serum resistin concentration and serum concentrations of leptin (proinflammatory adipokine) and adiponectin (anti-inflammatory adipokine). STUDY: A total of 23 male, nondiabetic patients with chronic pancreatitis of alcoholic origin and 16 healthy subjects were examined. Fasting blood samples were collected from patients in both groups. Serum resistin concentration was assayed by enzyme-linked immunosorbent assay. Serum adiponectin, leptin, and insulin concentrations were determined by radioimmunoassay. RESULTS: Serum resistin concentration was significantly higher in patients with chronic pancreatitis as compared with control subjects. In contrast, patients with chronic pancreatitis had lower serum leptin and insulin concentrations than healthy subjects. There were no statistically significant differences in serum adiponectin concentration between patients with pancreatitis and healthy subjects. CONCLUSIONS: The results presented in this paper indicate that chronic pancreatitis in human is associated with the increase in serum resistin concentration and with the decrease in serum leptin and insulin concentrations. It can be supposed that resistin, by stimulation of tumor necrosis factor-alpha synthesis in blood mononuclear cells and in macrophages, increases the concentration of tumor necrosis factor-alpha, which in turn activates stellate cells. Activated stellate cells can produce collagen, eventually resulting in the development of pancreatic fibrosis.


Assuntos
Adiponectina/sangue , Leptina/sangue , Pancreatite Crônica/fisiopatologia , Resistina/sangue , Adulto , Idoso , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Fibrose , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Fator de Necrose Tumoral alfa/metabolismo
9.
Neurosci Lett ; 444(3): 209-11, 2008 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-18760332

RESUMO

Several data indicate that hypothalamic fatty acid synthesis pathway plays an important role in the control of food intake and energy expenditure in rodents. However, the confirmation of its physiological relevance in regulation of feeding in human remains incomplete. For fatty acid synthesis pathway to function as regulator of energy balance in human hypothalamus, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and other lipogenic enzymes activities must be present. The presence of FAS in human hypothalamic neurons has been shown by immunohistochemistry, but quantitative studies on FAS activity there has not been performed so far. There is no available data concerning ACC activity in human hypothalamus. Thus, we investigated ACC and FAS (as well as other lipogenic enzymes) activities in human hypothalamus of subjects who died in car accidents. The results presented in this paper indicate that ACC and FAS activities are present in human hypothalamus and that these activities are 2- to 3-fold lower than in rat hypothalamus. Moreover, our data presented in this paper indicate that other lipogenic enzymes activities are also present in human hypothalamus. The activity of FAS, ACC and other lipogenic enzymes in human hypothalamus suggests that fatty acid synthesis actively occurs there. Therefore, it is likely, that in human this pathway may be relevant to hypothalamic functioning as food intake and energy expenditure regulator, similarly as it was suggested in rodents.


Assuntos
Acetil-CoA Carboxilase/metabolismo , Ácido Graxo Sintases/metabolismo , Hipotálamo/enzimologia , Animais , Feminino , Humanos , Masculino , Ratos
10.
Neurosci Lett ; 433(3): 174-7, 2008 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-18242853

RESUMO

Neuropeptide Y (NPY) is found in neurons of the brain and in the neurons that innervate abdominal organs including liver. Major biological function of hypothalamic NPY is regulation of appetite and body weight homeostasis. In the periphery, biological function of NPY varies, depending on the organ/tissue. Increased hypothalamic NPY mRNA level in response to chronic caloric restriction is a well documented phenomenon. The effect of food restriction on NPY mRNA level in neurons that innervate liver has not been published so far. To evaluate how chronic food restriction affects liver (and other abdominal organs) NPY mRNA level, we compared NPY mRNA abundance in liver, kidney cortex, perirenal white adipose tissue and in hypothalamus of rats maintained on chronic restricted diet. Data presented in this paper indicate that chronic food restriction: (a) caused the increase of NPY mRNA level in the hypothalamus, (b) caused the decrease of NPY mRNA level in the liver, and (c) was without effect on NPY mRNA level in kidney cortex and perirenal white adipose tissues. Moreover, rats maintained on restricted diet displayed lower serum NPY, leptin and insulin concentrations and higher serum corticosterone concentration. Together, these data suggest that hypothalamus and liver (and other abdominal organs) NPY gene expression is differentially regulated by caloric restriction. It seems that liver NPY gene expression in contrast to the hypothalamus NPY gene expression is not suppressed by leptin.


Assuntos
Privação de Alimentos/fisiologia , Hipotálamo/metabolismo , Fígado/metabolismo , Neurônios/metabolismo , Neuropeptídeo Y/genética , RNA Mensageiro/metabolismo , Tecido Adiposo/inervação , Tecido Adiposo/metabolismo , Animais , Regulação do Apetite/fisiologia , Vias Autônomas/fisiologia , Corticosterona/sangue , Regulação da Expressão Gênica/fisiologia , Hipotálamo/citologia , Insulina/sangue , Rim/inervação , Rim/metabolismo , Leptina/sangue , Fígado/inervação , Masculino , Ratos , Ratos Wistar , Regulação para Cima/fisiologia
11.
Anticancer Res ; 37(11): 6321-6327, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29061815

RESUMO

BACKGROUND/AIM: Pancreatic cancer is a disease with very poor prognosis, and none of currently available pharmacotherapies have proven to be efficient in this indication. The aim of this study was to analyze the expression of fatty acid synthase (FASN) gene as a potential therapeutic target in proliferating human pancreatic cancer cells (PANC-1), and verify if orlistat, originally developed as an anti-obesity drug, inhibits PANC-1 proliferation. MATERIALS AND METHODS: The effects of orlistat on gene expression, lipogenesis, proliferation and apoptosis was studied in PANC-1 cell culture. RESULTS: Expression of FASN increased during proliferation of PANC-1. Inhibition of FASN by orlistat resulted in a significant reduction of PANC-1 proliferation and enhanced apoptosis of these cells. CONCLUSION: This study showed, to our knowledge for the first time, that orlistat exhibits significant antitumor activity against PANC-1 cells. This implies that orlistat analogs with good oral bioavailability may find application in pharmacotherapy of pancreatic cancer.


Assuntos
Antineoplásicos/farmacologia , Ácido Graxo Sintase Tipo I/genética , Lactonas/farmacologia , Neoplasias Pancreáticas/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ácido Graxo Sintase Tipo I/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lipogênese/efeitos dos fármacos , Orlistate , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética
13.
Obes Surg ; 15(6): 803-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15978151

RESUMO

BACKGROUND: Human obesity is associated with increased serum hepatocyte growth factor (HGF) concentration. This study examines whether reduced body fat mass after vertical banded gastroplasty (VBG) is associated with a decrease in serum HGF concentration. METHODS: Serum HGF concentration and body weight, BMI, body fat mass, blood pressure, serum leptin, insulin, triacylglycerol, and cholesterol concentrations were studied in 10 obese women before and 1 year after VBG. 10 lean, healthy women were used as controls. RESULTS: Obese women showed significantly higher serum HGF concentration than control (lean, healthy) subjects. The mean serum HGF concentration decreased significantly 1 year after VBG, but did not reach the value observed in lean women. After VBG, BMI, body fat mass and serum HGF had similar patterns of decrease. Moreover, serum HGF concentration was positively correlated with both BMI (r=0.6, P<0.01) and body fat mass (r=0.6, P<0.01). Before surgery in obese women, elevated blood pressure was observed, which decreased after VBG. Linear regression analysis between blood pressure and serum HGF concentration using all subjects, showed no correlation between either systolic blood pressure and serum HGF concentration (r=.15, P=NS) or between diastolic blood pressure and serum HGF concentration (r=0.1, P=NS). Insulin resistance index (HOMA score), serum leptin, insulin and triacylglycerol concentrations decreased 1 year after VBG. However, serum cholesterol concentration did not change significantly. CONCLUSIONS: These results indicate that VBG results in a reduction in circulating HGF concentration. The reduced body fat mass may contribute in part to the decrease of serum HGF concentration after VBG. Because elevated serum HGF concentration may contribute to the progression of atherosclerosis, the decrease in serum HGF concentration after VBG may be beneficial for obese subjects.


Assuntos
Gastroplastia , Fator de Crescimento de Hepatócito/sangue , Obesidade Mórbida/sangue , Tecido Adiposo/metabolismo , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Período Pós-Operatório
14.
Exp Gerontol ; 38(4): 415-22, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12670628

RESUMO

To determine whether increase of serum leptin (the known natural inhibitor of lipogenic enzymes gene expression) concentration would account for the age-related decrease in lipogenesis (a) serum leptin concentration; (b) leptin mRNA abundance; (c) the rate of fatty acid synthesis in vivo; (d) lipogenic enzymes activity and (e) mRNA levels were assayed in white adipose tissue (WAT) of male young and old rats. We found that leptin mRNA abundance in WAT and serum leptin concentration was much lower in young than in old animals. In contrast, the rate of fatty acid synthesis in WAT was much higher in young animals. The old rats displayed much lower lipogenic enzymes activities (acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), ATP-citrate lyase (ACL), malic enzyme (ME), glucose 6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase 6PGDH) and mRNA abundance as compared to young rats. Considering the inverse relationship between serum leptin concentration and lipogenic enzymes genes expression and known inhibitory effect of leptin on lipogenic enzymes gene expression, one can conclude that the increase of ob gene expression could at least partly account for the reduced WAT lipogenic enzymes genes expression in old animals.


Assuntos
Tecido Adiposo/metabolismo , Envelhecimento/fisiologia , Desidrogenases de Carboidrato/metabolismo , Ácidos Graxos/biossíntese , Leptina/genética , ATP Citrato (pro-S)-Liase/genética , Acetil-CoA Carboxilase/genética , Animais , Ácido Graxo Sintases/genética , Expressão Gênica , Glucosefosfato Desidrogenase/genética , Malato Desidrogenase/genética , Masculino , Fosfogluconato Desidrogenase/genética , RNA Mensageiro/análise , Ratos , Ratos Wistar
15.
Metabolism ; 53(8): 1060-5, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15281019

RESUMO

Chronic renal failure (CRF) frequently results in hypertriglyceridemia and elevated plasma concentration of very-low-density lipoprotein (VLDL). These abnormalities are thought to be primarily due to depressed lipoprotein lipase and hepatic lipase activities, as well as impaired clearance of plasma lipoproteins. Some results suggest that not only lipoproteins catabolism but also their overproduction might contribute to hypertriglyceridemia in CRF. Because sterol regulatory element binding protein (SREBP) plays an important role in the regulation of lipid homeostasis, increased level of this transcription factor might be involved in modulating lipid metabolism in CRF. The purpose of the present study is to determine whether there is an altered regulation of the SREBP-1 in CRF rats and whether the altered regulation of SREBP-1 is associated with the upregulation of lipogenic enzymes genes expression in CRF rats. In the white adipose tissue (WAT) of CRF rats, marked increases in the microsomal (precursor) and nuclear (mature) forms of SREBP-1 have been found. The increase in SREBP-1 was associated with an increased level of lipogenic enzymes (acetyl-coenzyme A [CoA] carboxylase [ACC], adenosine triphosphate-citrate lyase [ACL], fatty acid synthase [FAS], glucose 6-phosphate dehydrogenase [G6PDH], 6-phosphogluconate dehydrogenase [6PGDH], and malic enzyme [ME]) genes expression. In turn, this was associated with an increased rate of fatty acids synthesis in WAT and a significant increase in plasma triacylglycerol (TAG) and VLDL concentration. Our study indicates that WAT SREBP-1 expression is increased in CRF rats and that SREBP-1 may play an important role in the increased fatty acid synthesis. These results reveal another facet of disturbed lipid metabolism in CRF.


Assuntos
Tecido Adiposo/enzimologia , Proteínas Estimuladoras de Ligação a CCAAT/biossíntese , Proteínas de Ligação a DNA/biossíntese , Falência Renal Crônica/enzimologia , Falência Renal Crônica/genética , Lipídeos/biossíntese , Fatores de Transcrição , Animais , Northern Blotting , Proteínas Estimuladoras de Ligação a CCAAT/genética , Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/genética , Ácidos Graxos/biossíntese , Testes de Função Renal , Cinética , Masculino , Microssomos/enzimologia , Microssomos/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar , Proteína de Ligação a Elemento Regulador de Esterol 1 , Triglicerídeos/sangue , Regulação para Cima
16.
Metabolism ; 51(12): 1605-10, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12489075

RESUMO

Hypertriglyceridemia associated with chronic renal failure (CRF) and elevated plasma concentration of very-low-density lipoprotein (VLDL) are thought to be a consequence of the depressed lipoprotein lipase and hepatic lipase activities and impaired clearance of lipoproteins. However, there is some evidence that the lipoproteins overproduction might also contribute to hypertriglyceridemia in CRF. This study was performed to test the hypothesis that the increased rate of lipogenesis consequent to upregulation of fatty acid synthase (FAS), a key lipogenic enzyme, gene expression could contribute to overproduction of triacylglycerols and to hypertriglyceridemia in CRF. FAS activity, FAS protein mass (Western blot analysis), and FAS mRNA level (Northern blot analysis) in liver and epididymal white adipose tissue (WAT) were measured in male Wistar rats 6 weeks after subtotal (5 of 6) nephrectomy or sham operation. Moreover, the rate of lipogenesis in WAT was determined. The CRF group showed significant increase in FAS gene expression (measured as activity, mRNA, and protein abundance) in both liver and WAT. This was associated with the increase in the lipogenesis rate and with the increase in plasma triacylglycerol and VLDL concentrations. Our results suggest that not only decreased removal, but also an increase of triacylglycerol production could contribute, in part, to the CRF-associated hyperlipidemia. Upregulation of FAS gene expression, shown in this report for the first time, reveals another factor involved in disturbed lipid metabolism in CRF. It seems that elevated plasma insulin and cytokine concentration could play an important role in the mechanism responsible for the increased FAS gene expression in CRF.


Assuntos
Ácido Graxo Sintases/genética , Expressão Gênica , Falência Renal Crônica/genética , Tecido Adiposo/metabolismo , Animais , Epididimo , Falência Renal Crônica/metabolismo , Falência Renal Crônica/fisiopatologia , Lipídeos/biossíntese , Lipoproteínas VLDL/sangue , Fígado/metabolismo , Masculino , Nefrectomia/métodos , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Triglicerídeos/sangue , Regulação para Cima
17.
Pol Merkur Lekarski ; 15(88): 322-3; discussion 323-5, 2003 Oct.
Artigo em Polonês | MEDLINE | ID: mdl-14974358

RESUMO

Lipid disorders are one of the known metabolic changes associated with chronic renal failure (CRF) [1, 2]. They are present as: hypertriglyceridemia--existed in 60% of CRF patients and hypercholesterolemia observed in 20-30% of people with this syndrome. These disorders, what was shown also in our own studies, are existing in different intensity in patients treated with maintenance haemodialysis [3], peritoneal dialysis [4] and after renal transplantation as well [5]. Mechanism of hypertriglyceridemia, despite over thirty years of studies, is still not finally elucidated. The opinion that it is a result of impaired triglyceride removal (due to decreased activities of both lipoprotein and hepatic lipases) is well documented, however the role of lipogenesis in its development is obscure [6, 7]. The reports concerning this problem contain contradictory data. In our studies performed several years ago we have shown that lipogenesis rate in white adipose tissue of uremic rats is significantly augmented [8, 9, 10] due to activation of free fatty acid synthase. Therefore, recently we paid once again our attention on the activity of this lipogenesis rate limiting enzyme responsible for the long term regulation. We measured its activity, protein abundance and mRNA level in liver and epididymal white adipose tissue of rats with surgically induced renal failure (two-stage subtotal nephrectomy). The results support the thesis that lipogenesis takes a part in a hypertriglyceridemia found in renal failure. There have been observed a significant increase in plasma triglyceride and VLDL concentrations in uremic animals and it was associated with the increase of FAS activity, FAS protein abundance and FAS mRNA. The results were similar in both studied tissues. Moreover, there have been also observed the increased activities of malic enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. All these enzymes participate in NADPH production, which is a necessary substrate for fatty acid biosynthesis [11, 12, 13]. Concluding, it appears that the rise in plasma triglyceride and VLDL concentrations observed in CRF rats is not only the result of increased liver and white adipose tissue lipogenesis rate. One has to remember, that these date are strictly original and enabling to elucidation further pathogenesis of hyperlipidemia in CRF. In the second set of experiments performed also in rats with experimentally induced CRF we have found that hypercholesterolemia observed in those animals is dependent on the significant activation of cholesterol synthase, induced by increased production of this enzyme (increment of protein abundance and synthase mRNA [14, 15]. Simultaneously, we have performed original studies on the diurnal rhythm of cholesterologenesis, showing that activity of this process is significantly augmented during whole twenty four hours [15]. Summarizing, one have to underline that our observations have important impact to the elucidation of lipid disturbances pathomechanism. Nevertheless further studies are necessary to establish how experimental data are corresponding with human pathology.


Assuntos
Hiperlipoproteinemias/complicações , Hiperlipoproteinemias/fisiopatologia , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Humanos , Hiperlipoproteinemias/metabolismo , Falência Renal Crônica/metabolismo , Lipase Lipoproteica/metabolismo , Fígado/metabolismo , NADP/sangue , Triglicerídeos/sangue
18.
Regul Pept ; 173(1-3): 55-9, 2012 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-21971116

RESUMO

Chemerin is an adipokine associated with metabolic syndrome, systemic inflammation and innate immune system. It has been suggested recently that the decrease in renal function may cause an increase in serum chemerin concentration. In this paper we investigated the effect of kidney transplantation on elevated serum chemerin concentration in dialyzed patients with end stage renal disease (ESRD). Twenty five ESRD patients were tested before and 3months after the kidney transplantation. The control group was comprised of twenty one healthy subjects. Serum chemerin concentrations were measured using commercial ELISA kit, and were related to clinical status, and biomarkers of renal function. We have shown that the kidney transplantation resulted in the decrease of the serum chemerin concentration. Concomitantly, serum creatinine, blood urea nitrogen, phosphate and C-reactive protein concentrations were significantly reduced, while estimated glomerular filtration rate (eGFR), calcium and hemoglobin substantially increased. Univariate regression analysis showed that serum chemerin concentration was positively correlated with serum creatinine and phosphate concentrations and negatively correlated with eGFR. The results presented here indicate that the serum chemerin concentration in patients with ESRD normalizes after the kidney transplantation, and provide additional evidence that serum chemerin concentration is related to renal function.


Assuntos
Quimiocinas/sangue , Falência Renal Crônica/sangue , Transplante de Rim , Recuperação de Função Fisiológica , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Rim/fisiopatologia , Rim/cirurgia , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Obes Surg ; 21(10): 1634-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21618064

RESUMO

Bariatric surgery significantly reduces the risk of cardiovascular diseases but has no effects on hyperhomocysteinemia, the risk factor for atherogenesis. We hypothesize that the decrease in serum betaine (involved in homocysteine metabolism) concentrations, after bariatric surgery, impairs conversion of homocysteine to methionine, leading to hyperhomocysteinemia. If this is true, it may be desirable to supply patients after bariatric surgery with betaine. Serum betaine and homocysteine concentrations were measured by liquid chromatography/mass spectrometry, in 16 obese patients, before and 6 months after bariatric surgery. Ten healthy individuals with normal body mass index served as controls. Serum betaine concentrations decreased to the values lower than in controls after bariatric surgery, whereas serum homocysteine concentrations remained elevated. In patients supplemented with B(12) and folate, no effect of bariatric surgery on serum concentrations of vitamins involved in homocysteine metabolism was observed. These results suggest that betaine deficit could be responsible for maintenance of hyperhomocysteinemia after bariatric surgery. We postulate that supplementation with betaine could be of therapeutic value for the treatment of hyperhomocysteinemia after bariatric surgery.


Assuntos
Cirurgia Bariátrica , Betaína/sangue , Obesidade/sangue , Adulto , Feminino , Homocisteína/sangue , Homocisteína/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia
20.
World J Gastroenterol ; 16(35): 4422-7, 2010 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-20845509

RESUMO

AIM: To investigate the influence of chronic pancreatitis (CP) on serum concentrations of amino acids. METHODS: Thirty-five male patients with alcoholic CP and 21 healthy male subjects were examined. Serum concentrations of amino acids were assayed by ion-pair high-performance liquid chromatography with mass detection. RESULTS: Serum glutamate concentration was increased in CP patients as compared to controls. In contrast, serum concentrations of glutamine, histidine, tyrosine, proline, tryptophan and threonine were significantly decreased in CP patients. A trend towards decreasing concentrations of serum lysine, alanine, methionine and valine as well as for total serum amino acids was observed. The sum of aromatic and the sum of essential amino acid concentrations were significantly lower in CP patients than in controls. CONCLUSION: CP leads to decreased serum concentrations of several amino acids, such as essential and aromatic serum amino acids, most likely due to decreased exocrine function.


Assuntos
Aminoácidos Aromáticos/sangue , Aminoácidos Essenciais/sangue , Pancreatite Crônica/sangue , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade
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