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1.
Chinese Journal of Hepatology ; (12): 742-749, 2023.
Article in Chinese | WPRIM | ID: wpr-986204

ABSTRACT

Objective: To detect the therapeutic efficacy of FGF21 analogues on the zebrafish model of non-alcoholic fatty liver disease. Methods: A zebrafish model of non-alcoholic fatty liver disease was established by providing the normal diet fed to wild-type zebrafish three times daily. PF-05231023 was administered exogenously at a final concentration of 0.5 μmol/L. Body length, body weight, triglycerides, and other indexes were measured after 20 days. Pathological changes were evaluated in liver tissue sections by HE staining. Quantitative PCR was used to identify expressional changes in genes related to lipid metabolism, endoplasmic reticulum stress, and inflammation. Results: QPCR and immunofluorescence staining results showed that FGF21 was highly expressed in the zebrafish model group. The addition of the FGF21 analogue PF-05231023 significantly reduced the body length and body weight (P < 0.01), and the triglyceride content (P < 0.05) in the zebrafish model group. The liver HE staining results showed that PF-05231023 had alleviated the large and tiny bullae fat, lesions, and others in the zebrafish model group. The quantitative PCR results demonstrated that PF-05231023 reduced the expression of lipogenic factors (P < 0.01), inflammatory-related factors (P < 0.001), and genes related to endoplasmic reticulum stress (P < 0.05), but raised lipid-oxidation-related factors (P < 0.05) in the zebrafish model group. The addition of PF-05231023 reduced oleic acid-induced lipid and triglyceride levels in HepG2 cells. Conclusion: FGF21 analogue addition can improve indexes in the zebrafish disease model of non-alcoholic fatty liver disease.


Subject(s)
Animals , Body Weight , Diet, High-Fat , Lipids , Liver/pathology , Non-alcoholic Fatty Liver Disease/pathology , Triglycerides/metabolism , Zebrafish/metabolism , Zebrafish Proteins
2.
Journal of Zhejiang University. Medical sciences ; (6): 306-317, 2023.
Article in English | WPRIM | ID: wpr-982048

ABSTRACT

OBJECTIVES@#To investigate the effect and mechanism of lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) targeting Cyp2e1 gene on subacute alcoholic liver injury in mice.@*METHODS@#siRNA targeting Cyp2e1 gene was encapsulated in LNP (si-Cyp2e1 LNP) by microfluidic technique and the resulting LNPs were characterized. The optimal dose of si-Cyp2e1 LNP administration was screened. Forty female C57BL/6N mice were randomly divided into blank control group, model control group, si-Cyp2e1 LNP group, LNP control group and metadoxine group. The subacute alcoholic liver injury mouse model was induced by ethanol feeding for 10 d plus ethanol gavage for the last 3 d. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and the superoxide dismutase (SOD) activity as well as malondialdehyde, reactive oxygen species, glutathione, triacylglycerol, total cholesterol contents in liver tissue were measured in each group, and liver index was calculated. The expression of genes related to oxidative stress, lipid synthesis and inflammation in each group of mice were measured by realtime RT-PCR.@*RESULTS@#Compared with the model control group, the levels of liver index, serum ALT, AST activities, malondialdehyde, reactive oxygen species, triacylglycerol, total cholesterol contents in liver tissue decreased, but the SOD activity as well as glutathione increased in the si-Cyp2e1 LNP group (all P<0.01). Hematoxylin-eosin staining result showed disorganized hepatocytes with sparse cytoplasm and a large number of fat vacuoles and necrosis in the model control group, while the si-Cyp2e1 LNP group had uniformly sized and arranged hepatocytes with normal liver tissue morphology and structure. Oil red O staining result showed si-Cyp2e1 LNP group had lower fat content of the liver compared to the model control group (P<0.01), and no fat droplets accumulated. Anti-F4/80 monoclonal antibody fluorescence immunohistochemistry showed that the si-Cyp2e1 LNP group had lower cumulative optical density values compared to the model control group (P<0.01) and no significant inflammatory reaction. Compared with the model control group, the expression of catalytic genes P47phox, P67phox and Gp91phox were reduced (all P<0.01), while the expression of the antioxidant enzyme genes Sod1, Gsh-rd and Gsh-px were increased (all P<0.01). The mRNA expression of the lipid metabolism genes Pgc-1α and Cpt1 were increased (all P<0.01) and the lipid synthesis-related genes Srebp1c, Acc and Fasn were decreased (all P<0.01); the expression of liver inflammation-related genes Tgf-β, Tnf-α and Il-6 were decreased (all P<0.01).@*CONCLUSIONS@#The si-Cyp2e1 LNP may attenuate subacute alcoholic liver injury in mice mainly by reducing reactive oxygen levels, increasing antioxidant activity, blocking oxidative stress pathways and reducing ethanol-induced steatosis and inflammation.


Subject(s)
Animals , Female , Mice , Antioxidants/metabolism , Cholesterol/metabolism , Ethanol/pharmacology , Glutathione/pharmacology , Inflammation , Lipids/pharmacology , Liver , Malondialdehyde/pharmacology , Mice, Inbred C57BL , Oxidative Stress , Reactive Oxygen Species/metabolism , RNA, Small Interfering/pharmacology , Superoxide Dismutase , Triglycerides/metabolism , Cytochrome P-450 CYP2E1/metabolism
3.
China Journal of Chinese Materia Medica ; (24): 525-533, 2023.
Article in Chinese | WPRIM | ID: wpr-970489

ABSTRACT

This study aimed to investigate the recovery effect of Zuogui Jiangtang Qinggan Prescription on intestinal flora homeostasis control and intestinal mucosal barrier in type 2 diabetes mellitus(T2DM) with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. NAFLD was established in MKR transgenic mice(T2DM mice) by a high-fat diet(HFD), and subsequently treated for 8 weeks with Zuogui Jiangtang Qinggan Prescription(7.5, 15 g·kg~(-1)) and metformin(0.067 g·kg~(-1)). Triglyceride and liver function were assessed using serum. The hematoxylin-eosin(HE) staining and Masson staining were used to stain the liver tissue, while HE staining and AB-PAS staining were used to stain the intestine tissue. 16S rRNA sequencing was utilized to track the changes in the intestinal flora of the mice in each group. Polymerase chain reaction(PCR) and immunofluorescence were used to determine the protein and mRNA expression levels of ZO-1, Occludin, and Claudin-1. The results demonstrated that Zuogui Jiangtang Qinggan Prescription increased the body mass of T2DM mice with NAFLD and decreased the hepatic index. It down-regulated the serum biomarkers of liver function and dyslipidemia such as alanine aminotransferase(ALT), aspartate transaminase(AST), and triglycerides(TG), increased insulin sensitivity, and improved glucose tolerance. According to the results of 16S rRNA sequencing, the Zuogui Jiangtang Qinggan Prescription altered the composition and abundance of the intestinal flora, increasing the relative abundances of Muribaculaceae, Lactobacillaceae, Lactobacillus, Akkermansia, and Bacteroidota and decreasing the relative abundances of Lachnospiraceae, Firmicutes, Deslfobacteria, Proteobacteria, and Desulfovibrionaceae. According to the pathological examination of the intestinal mucosa, Zuogui Jiangtang Qinggan Prescritpion increased the expression levels of the tight junction proteins ZO-1, Occludin, and Claudin-1, promoted intestinal mucosa repair, protected intestinal villi, and increased the height of intestinal mucosa villi and the number of goblet cells. By enhancing intestinal mucosal barrier repair and controlling intestinal microbiota homeostasis, Zuogui Jiangtang Qinggan Prescription reduces intestinal mucosal damage induced by T2DM and NAFLD.


Subject(s)
Mice , Animals , Non-alcoholic Fatty Liver Disease/metabolism , Gastrointestinal Microbiome , RNA, Ribosomal, 16S , Diabetes Mellitus, Type 2/metabolism , Occludin/pharmacology , Claudin-1/metabolism , Intestinal Mucosa , Liver , Triglycerides/metabolism , Diet, High-Fat , Homeostasis , Mice, Inbred C57BL
4.
China Journal of Chinese Materia Medica ; (24): 1795-1802, 2021.
Article in Chinese | WPRIM | ID: wpr-879094

ABSTRACT

This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.


Subject(s)
Animals , Rats , Biological Transport , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Hyperlipidemias/metabolism , Liver/metabolism , Rats, Sprague-Dawley , Triglycerides/metabolism
5.
Acta Paul. Enferm. (Online) ; 32(6): 608-616, Nov.-Dez. 2019. tab, graf
Article in Portuguese | LILACS, BDENF | ID: biblio-1054620

ABSTRACT

Resumo Objetivo Analisar as alterações clínicas, metabólicas e sua relação com a resistência à insulina entre adolescentes. Métodos Estudo analítico, realizado com 357 adolescentes de escolas públicas estaduais de um município do Nordeste brasileiro. O formulário aplicado continha as variáveis Índice de Massa Corporal, Circunferência da Cintura, Circunferência do Pescoço, Índice de Conicidade, Pressão Arterial Média; Triglicerídeos, Glicemia, High — Density Lipoprotein Coiesteroi, Insulina e Índice Homeostasis Model Assessment, analisadas por medidas descritivas para variáveis quantitativas; e frequências para variáveis qualitativas. Foram realizados testes de associações através do Qui-quadrado e do teste Odds Ratio. Resultados A prevalência de resistência à insulina foi de 33,9%. As médias da circunferência da cintura, circunferência do pescoço, índice de conicidade, pressão arterial sistólica média e pressão arterial diastólica média estiveram elevadas respectivamente em 4,2%; 30%; 10,9%; 4,2% e 14% dos adolescentes. Os níveis de High - Density Lipoprotein colesterol estiveram diminuídos em 30,5% da amostra, ao passo que os triglicerídeos estavam elevados em 18,8%. Não foi identificada alteração na glicemia. Aqueles que apresentaram índice de massa corporal, circunferência da cintura, circunferência do pescoço, índice de conicidade e triglicerídeos com valores alterados possuíam maiores chances de apresentar resistência à insulina (OD: 3,62; 11,54; 3,50; 4,49; 3,05, respectivamente). De maneira oposta, os adolescentes com pressão arterial sistólica média, pressão arterial diastólica média e High — Density Lipoprotein colesterol alterados não apresentaram significância estatística (p<0,05). Conclusão A resistência à insulina está presente entre os adolescentes, com associações positivas e significativas com alterações clínicas e metabólicas.


Resumen Objetivo Analizar las alteraciones clínicas, metabólicas y la relación con la resistencia a la insulina en adolescentes. Métodos Estudio analítico, realizado con 357 adolescentes de escuelas públicas provinciales/departamentales de un municipio del Nordeste brasileñ?o. El formulario aplicado contenía las variables: índice de masa corporal, circunferencia de la cintura, circunferencia del cuello, índice de conicidad, presión arterial promedio, triglicéridos, glucemia, colesterol High-Density Lipoprotein, insulina e índice Homeostasis Model Assessment Las variables cuantitativas fueron analizadas mediante medidas descriptivas, y las variables cualitativas mediante frecuencias. Se realizaron pruebas de relaciones a través de la prueba ?2 de Pearson y Odds Ratio. Resultados La prevalencia de resistencia a la insulina fue de 33,9%. Los promedios de circunferencia de la cintura, circunferencia del cuello, índice de conicidad, presión arterial sistólica promedio y presión arterial diastólica promedio fueron altos respectivamente en el 4,2%; 30%; 10,9%; 4,2% y 14% de los adolescentes. Los niveles de colesterol High-Density Lipoprotein fueron bajos en el 30,5% de la muestra, mientras que los triglicéridos fueron altos en el 18,8%. No se identificó alteración en la glucemia. Los que presentaron índice de masa corporal, circunferencia de la cintura, circunferencia del cuello, índice de conicidad y triglicéridos con valores alterados tenían mayores chances de presentar resistencia a la insulina (OD: 3,62; 11,54; 3,50; 4,49; 3,05, respectivamente). De forma contraria, los adolescentes con presión arterial sistólica promedio, presión arterial diastólica promedio y colesterol High-Density Lipoprotein alterados no presentaron significación estadística. Conclusión La resistencia a la insulina está presente en los adolescentes, con una relación positiva y significativa respecto a alteraciones clínicas y metabólicas.


Abstract Objective Analyzing the clinical and metabolic alterations and their relation to insulin resistance among adolescents. Methods Analytic study, carried out with 357 adolescents of state public schools in a municipality in Northeastern Brazil. The applied form contained the variables Body Mass index, Waist Circumference, Neck Circumference, Taper index, Average Blood Pressure, Triglycerides, Blood Sugar Level, High-Density Lipoprotein Cholesterol, insulin, and Homeostasis Model Assessment Index, analyzed through descriptive measures for quantitative variables; and through frequency for qualitative variables. Association tests were made through Chi-Square test and through Odds Ratio. Results Prevalence of insulin resistance was 33.9%. The average values of waist circumference, neck circumference, taper index, average systolic blood pressure and average diastolic blood pressure were high in, respectively, 4.2%, 30%, 10.9%, 4.2% and 14% of adolescents. High-Density Lipoprotein Cholesterol levels were decreased in 30.5% of the sample, whereas triglycerides were high in 18.8%. No blood sugar alteration was identified. Those who presented altered values for body mass index, waist circumference, neck circumference, taper index, and triglycerides had higher chances to present insulin resistance (OD: 3.62, 11.54, 3.50, 4.49, 3.05, respectively). On the other hand, adolescents with altered average systolic blood pressure, average diastolic blood pressure and High-Density Lipoprotein Cholesterol did not present statistical significance (p<0.05). Conclusion Insulin resistance is present among adolescents, with positive and significant association to clinical and metabolic alterations.


Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Insulin Resistance , Anthropometry , Risk Factors , Obesity , Triglycerides/metabolism , Epidemiologic Studies , Laboratory and Fieldwork Analytical Methods , Chronic Disease , Lipid Metabolism , Evaluation Studies as Topic , Glucose/metabolism , Cholesterol, HDL/metabolism
6.
Medicina (B.Aires) ; 78(2): 91-98, abr. 2018. ilus
Article in Spanish | LILACS | ID: biblio-954956

ABSTRACT

En la diabetes mellitus tipo 2 el aumento en la producción de quilomicrón en el estado post-prandial se asocia a mayor riesgo cardiovascular. La evidencia actual posiciona al enterocito como actor principal en la dislipemia de la diabetes mellitus tipo 2 debido a que aumenta la producción de apolipoproteína B-48 en respuesta a una elevación de ácidos grasos libres y glucosa. El metabolismo del quilomicrón se encuentra regulado por múltiples factores independientes además de la ingesta de grasa alimentaria. Entre estos factores se destacan las hormonas intestinales, como el péptido similar al glucagón tipo 1 que disminuye la producción de apolipoproteína B-48 y el péptido similar al glucagón tipo 2 que la aumenta. Por otro lado, la insulina inhibe de forma aguda la producción de quilomicrón en el sujeto sano mientras que en la diabetes mellitus tipo 2, este efecto está ausente. La comprensión de los factores reguladores emergentes de la secreción de quilomicrón permite vislumbrar nuevos mecanismos de control en su metabolismo y aportar estrategias terapéuticas focalizadas en la hiperlipidemia posprandial en la diabetes mellitus tipo 2 con la reducción del riesgo cardiovascular.


In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.


Subject(s)
Humans , Chylomicrons/metabolism , Enterocytes/metabolism , Diabetes Mellitus, Type 2/metabolism , Dyslipidemias/metabolism , Triglycerides/metabolism , Insulin Resistance , Postprandial Period , Diabetes Mellitus, Type 2/complications , Dyslipidemias/complications , Glucagon-Like Peptide 1/metabolism
7.
Braz. j. med. biol. res ; 51(6): e7342, 2018. graf
Article in English | LILACS | ID: biblio-889108

ABSTRACT

Early weaning (EW) leads to overweight, visceral obesity, hyperleptinemia, and insulin resistance in adulthood. Treatment with Ilex paraguariensis (yerba mate) improves obesity and insulin resistance in these animals. Here, we evaluated the effects of chronic treatment with yerba mate on the redox balance and liver morphology of overweight early-weaned rats. To induce EW, we wrapped the dams with bandages to interrupt milk access during the last 3 days of lactation. Control pups (C) had free access to maternal milk for the full 21 days of lactation. On postnatal day (PN) 150, EW offspring were subdivided into the EW+YM group, which received the aqueous extract of yerba mate (1 g/kg bw by gavage once a day for 30 days) and the EW group, which received water by gavage for the same period. All rats were euthanized on PN180. The EW group showed higher bound carbonyl (a marker of total protein oxidation), higher TBARS levels (a marker of lipid peroxidation), and lower superoxide dismutase (SOD) activity in liver tissue than the C group, as well as higher triglyceride content and microsteatosis. In plasma, the EW offspring showed higher TBARS levels. One month of yerba mate treatment normalized these parameters. Thus, we have shown evidence that yerba mate improved antioxidant defenses and mitigated liver dysfunction in overweight adult rats that were weaned prematurely.


Subject(s)
Animals , Male , Female , Rats , Fatty Liver/prevention & control , Ilex paraguariensis/chemistry , Overweight/prevention & control , Plant Extracts/pharmacology , Triglycerides/metabolism , Weaning , Fatty Liver/etiology , Insulin Resistance , Overweight/etiology , Oxidation-Reduction/drug effects , Rats, Wistar
8.
Arch. latinoam. nutr ; 66(4): 279-286, dic. 2016. ilus
Article in Spanish | LILACS, LIVECS | ID: biblio-838454

ABSTRACT

La dislipidemia es un factor de riesgo para el desarrollo de enfermedades cardiovasculares, una de las principales causas de muertes a nivel mundial. En este trabajo se estudió el efecto del aguacate (Persea americana) sobre el metabolismo lipídico de ratones normo e hiperlipémicos inducidos con dieta hiperlipídica. Ratones machos, fueron distribuidos en 4 grupos DE (dieta estándar), DEa (dieta estándar y aguacate); DH (dieta hiperlipídica) y DHa (dieta hiperlipídica y aguacate) y observados por 28 días. Luego de este periodo se determinaron los niveles de Colesterol Total, Triglicéridos y col-HDL y se calcularon los valores de col-LDL, VLDL e índices de riesgo aterogénico y de riesgo coronario. El grupo DH mostró niveles de CT, TG, col-LDLy VLDL significativamente superiores (p<0,001) a los valores alcanzados en el grupo DE. En los grupos DHa y DEa se redujeron significativamente (p<0,001) las concentraciones de CT, TG, col-LDL y VLDL, en comparación al grupo DH. Los grupos DEa y DHa difieren significativamente (p<0,005) en el nivel de CT, éste último presenta valores más bajos, los otros parámetros cuantificados no mostraron diferencias significativas. No hubo diferencias significativas para los valores del col-HDL en ningún grupo de estudio. La inducción a la hiperlipemia con un modelo de dieta hiperlipídica, generó incrementos importantes en el CT, TG, col-LDL y VLDL, además de aumentar el riesgo aterogénico. El consumo de la pulpa de aguacate redujo los niveles de CT, TG, col-LDL, VLDL y el índice de riesgo aterogénico en el grupo de ratones hiperlipémicos(AU)


Influence of avocado (Persea americana) pulp consumption on lipid metabolism in normolipidemic and diet induced hyperlipidemic mice . Dyslipidemia is a risk factor for developing cardiovascular disease, a major cause of deaths worldwide. The aim of this work is to study the effect of avocado (Persea americana), on lipid metabolism on normolipidemic and hyperlipidemic mice induced with high fat diet. Four groups of animals receiving standard diet (DE), standard and avocado diet (DEa), high fat diet (DH) and high fat and avocado diet (DHA) were used. All animals were observed for a period of 28 days. Blood sample was obtained at the end of experimentation period by cardiac puncture on anesthetized animals, and the levels of Cholesterol, triglycerides and col-HDL were de- termined and c-LDL, VLDL and atherogenic and coronary risk factors were calculated. DH group showed levels of TC, TG, c-LDL and VLDL significantly higher (p<0,001) than the values achieved in DHa group. DHa and DEa plasmatic values of TC, TG, c-LDL and VLDL were significantly reduced (p <0.001) compared to DH group. DEa and DHA groups differed significantly (p <0.005) in the level of CT, the latter has lower values, the other quantified parameters showed no significant differences. There were no significant differences for c-HDL values in any group. Hyperlipidemia induction with a model of high fat diet produced significantly increasing values of TC, TG, c-LDL and VLDL, besides of increasing the atherogenic risk. The benefit of avocado pulp consists in reduction of TC, TG, c-LDL, VLDL and the index of atherogenic risk(AU)


Subject(s)
Mice , Triglycerides/metabolism , Cardiovascular Diseases/etiology , Cholesterol/metabolism , Persea , Lipid Metabolism , Eating , Dyslipidemias , Diet, High-Fat
9.
Braz. j. med. biol. res ; 49(3): e5003, Mar. 2016. tab, graf
Article in English | LILACS | ID: lil-771936

ABSTRACT

Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.


Subject(s)
Animals , Male , Baccharis/chemistry , Caffeic Acids/administration & dosage , Coumaric Acids/administration & dosage , Metabolic Syndrome/prevention & control , Protective Agents/administration & dosage , Caffeic Acids/chemistry , Cholesterol/metabolism , Coumaric Acids/chemistry , Diet, High-Fat/adverse effects , Drug Therapy, Combination/methods , Fatty Liver/metabolism , Fatty Liver/pathology , Metabolic Syndrome/drug therapy , Mice, Inbred C57BL , Models, Animal , Protective Agents/chemistry , Triglycerides/metabolism
10.
Arq. gastroenterol ; 52(3): 210-215, July-Sep. 2015. tab
Article in English | LILACS | ID: lil-762872

ABSTRACT

BackgroundIn cirrhosis the production of cholesterol and lipoproteins is altered.ObjectiveEvaluate the lipid profile by measuring total cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein and triglyceride levels in patients with cirrhosis caused by alcoholism and/or hepatitis C virus infection and determine its association with Child-Pugh and MELD scores.MethodsCross-sectional retrospective study of patients treated at the outpatient clinic in Porto Alegre, Brazil, from 2006 to 2010.ResultsIn total, 314 records were reviewed, and 153 (48.7%) met the inclusion criteria, of which 82 (53.6%) had cirrhosis that was due to hepatitis C virus infection, 50 (32.7%) were due to alcoholism, and 21 (13.7%) were due to alcoholism and hepatitis C virus infection. The total cholesterol levels diminished with a Child-Pugh progression (P<0.001). Child-Pugh C was significantly associated with lover levels of low-density lipoprotein (<70 mg/dL; P<0.001), high-density lipoprotein (<40 mg/dL; P<0.001) and triglyceride (<70 mg/dL; P=0.003). MELD>20 was associated with lower total cholesterol levels (<100mg/dL; P<0.001), very low-density lipoprotein (<16 mg/dL; P=0.006), and low-density lipoprotein (<70 mg/dL; P=0.003). Inverse and statistically significant correlations were observed between Child-Pugh and all the lipid fractions analyzed (P<0.001). The increase in MELD was inversely correlated with reduced levels intotal cholesterol (P<0.001), high-density lipoprotein (P<0.001), low-density lipoprotein (P<0.001), very low-density lipoprotein (P=0.030) and triglyceride (P=0.003).ConclusionA reduction in the lipid profile in patients with cirrhosis due to hepatitis C virus infection and/or alcoholism was significantly associated with the Child-Pugh and MELD prognostic markers. These results suggest that the lipid profile may be used as a tool to assist in evaluating liver disease.


ContextoNa cirrose a produção de colesterol e de lipoproteínas está alterada.ObjetivoAvaliar o perfil lipídico - através da dosagem do colesterol total, lipoproteína de muito baixa densidade, lipoproteína de baixa densidade, lipoproteína de alta densidade e triglicerídeos - de pacientes com cirrose, por álcool e/ou vírus da hepatite C, e verificar sua associação com os escores Child-Pugh e MELD.MétodosEstudo transversal, retrospectivo de pacientes em acompanhamento ambulatorial no Complexo Hospitalar Santa Casa de Porto Alegre, Brasil, no período de 2006 a 2010.ResultadosForam revisados 314 prontuários, destes 153 (48,7%) preencheram os critérios de inclusão, sendo que 82 (53,6%) tinham cirrose por vírus da hepatite C, 50 (32,7%) por álcool e 21 (13,7%) por álcool e vírus da hepatite C. Os níveis de colesterol total reduziram com a progressão do Child-Pugh (P<0,001). Child-Pugh C associou-se significativamente aos níveis mais baixos de lipoproteína de baixa densidade (<70 mg/dL; P<0,001), lipoproteína de alta densidade (<40 mg/dL; P<0,001) e triglicerídeos (<70 mg/dL; P=0,003). MELD>20 esteve associado aos menores valores de colesterol total (<100 mg/dL; P<0,001), lipoproteína de muito baixa densidade (<16 mg/dL; P=0,006), lipoproteína de baixa densidade (<70 mg/dL; P=0,003). Correlações inversas e estatisticamente significativas foram observadas entre Child-Pugh e todas as frações lipídicas analisadas (P<0,001). O aumento do MELD esteve correlacionado inversamente com a redução do colesterol total (P<0,001), lipoproteína de alta densidade (P<0,001), lipoproteína de baixa densidade (P<0,001), lipoproteína de muito baixa densidade (P=0,030) e triglicerídeos (P=0,003).ConclusãoA redução do perfil lipídico, nos pacientes com cirrose por vírus da hepatite C e ou álcool, associou-se significativamente com os marcadores de prognóstico Child-Pugh e MELD. Tais resultados sugerem que o perfil lipídico poderá ser utilizado como uma ferramenta para auxiliar na avaliação da hepatopatia.


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Lipids/blood , Liver Cirrhosis/blood , Alcoholism/complications , Brazil , Cross-Sectional Studies , Cholesterol/metabolism , Hepatitis C/complications , Prognosis , Retrospective Studies , Triglycerides/metabolism
11.
Arq. bras. endocrinol. metab ; 58(8): 783-797, 11/2014. tab, graf
Article in English | LILACS | ID: lil-729785

ABSTRACT

The clinical manifestations of lipodystrophy syndromes (LS) are hypoleptinemia, hyperglycemia, insulin resistance, dyslipidemia and hepatic steatosis. Leptin replacement therapy (LRT) is effective at improving these pathologies. Currently, there are no data compiling the evidence from the literature, and demonstrating the effect of LRT in LS patients. A systematic review of the MEDLINE and Cochrane Library databases was conducted to identify studies assessing the effect of LRT on metabolic and hepatic endpoints in patients with LS not associated with highly active antiretroviral therapy (HAART) use. Standardized mean differences (SMD) and 95% confidence intervals of pooled results were calculated for overall changes in glucose homeostasis, lipid profile, and hepatic physiology, using an inverse-variance random-effects model. After screening, 12 studies were included for review. Meta-analysis of results from 226 patients showed that LRT decreased fasting glucose [0.75 SMD units (range 0.36‐1.13), p=0.0001], HbA1c [0.49 (0.17‐0.81), p=0.003], triglycerides [1.00 (0.69‐1.31), p<0.00001], total cholesterol [0.62 (0.21‐1.02), p=0.003], liver volume [1.06 (0.51‐1.61), p=0.0002] and AST [0.41 (0.10‐0.73) p=0.01]. In patients with non-HAART LS, LRT improves the outcome of several metabolic and hepatic parameters. Studies were limited by small populations and therefore large prospective trials are needed to validate these findings.


As manifestações clínicas das síndromes lipodistróficas (SL) incluem hipoleptinemia, hiperglicemia, resistência insulínica, dislipidemia e esteatose hepática. A terapia de reposição de leptina (TRL) melhora tais parâmetros, mas atualmente não há dados compilados demonstrando tal efeito. Uma revisão sistemática dos bancos de dados MEDLINE e Cochrane Library identificou estudos avaliando os efeitos da TRL sobre parâmetros metabólicos e hepáticos em pacientes com SL não associadas ao uso de antirretrovirais. Diferenças médias padronizadas (DMP) e intervalos de confiança de 95% foram calculados a partir dos resultados, para os efeitos da TRL sobre a homeostase da glicose, perfil lipídico, e morfologia/função hepática, usando um modelo de variação inversa e efeitos randômicos. Após a triagem, 12 estudos foram incluídos para revisão. A metanálise dos resultados de 226 pacientes mostrou que a TRL reduziu a glicemia de jejum [0,75 DMP (amplitude 0,36‐1,13), p=0,0001], HbA1c [0,49 (0,17‐0,81), p=0,003], triglicerídeos [1,00 (0,69‐1,31), p<0,00001], colesterol total [0,62 (0,21‐1,02), p=0,003], volume hepático [1,06 (0,51‐1,61), p=0,0002] e AST [0,41 (0,10‐0,73), p=0,001]. Em pacientes com SL não associada ao uso de antirretrovirais, a TRL melhora vários parâmetros metabólicos e hepáticos. Os estudos avaliados foram limitados pelo pequeno número de pacientes. Maiores estudos clínicos prospectivos são necessários para validar tais achados.


Subject(s)
Humans , Hormone Replacement Therapy , Leptin/therapeutic use , Lipodystrophy/drug therapy , Antiretroviral Therapy, Highly Active , Blood Glucose/metabolism , Cholesterol/metabolism , Fatty Liver/drug therapy , Fatty Liver/metabolism , Glycated Hemoglobin/metabolism , Insulin/metabolism , Leptin/deficiency , Leptin/metabolism , Lipodystrophy/metabolism , Liver/metabolism , Syndrome , Serum Albumin/metabolism , Transaminases/metabolism , Triglycerides/metabolism
12.
Rev. bras. cir. plást ; 29(3): 456-466, jul.-sep. 2014.
Article in English, Portuguese | LILACS | ID: biblio-748

ABSTRACT

A lipoaspiração permanece como um dos procedimentos mais realizados pelos cirurgiões plásticos (1-3). O aumento da segurança no ambiente cirúrgico, o refinamento da técnica e a satisfação das pacientes contribuem para a popularidade desta intervenção idealizada por Ilouz, em 1979 (4). Tem-se observado, ainda, tanto no ambiente médico quanto na mídia, uma crescente preocupação não apenas com a nova forma dos pacientes, mas também com a segurança. O tecido adiposo atua como um verdadeiro órgão endócrino e é o principal depósito de triglicerídeos, que têm uma relação clássica com doença aterosclerótica e resistência insulínica (6, 7). Estudos recentes ligaram ainda o metabolismo lipídico dos adipócitos à manutenção de um estado inflamatório sistêmico de baixo grau, através de vários mediadores (8-10). Há evidências científicas (11) que mostram o aumento do percentual de obesos em nosso país e uma importante taxa de pessoas, com sobrepeso. Este estudo também relaciona a prevalência de diabetes e de hipertensão. A clássica inter-relação entre a quantidade de gordura corporal e as chamadas doenças metabólicas tem suscitado a investigação dos elementos envolvidos neste processo e de tratamentos para o controle dos mesmos. A descoberta da leptina na década de 1990 (12) chamou a atenção para a propriedade reguladora do tecido adiposo. Estudos posteriores (5, 13) relacionaram ainda a síntese de outros fatores. Decidimos fazer uma revisão da literatura para esclarecer o estágio atual das pesquisas, tentando ordená-las de forma didática para melhor compreensão e auxílio para uma conduta mais segura e eficiente nos pacientes submetidos à lipoaspiração.


Liposuction is one of the most frequently performed procedures by plastic surgeons. The increased safety associated with the surgical settings, technical refinements, and level of patient satisfaction have contributed to the popularity gained by this intervention since it was first introduced by Ilouz in 1979 (4). Moreover, among medical communities and the media, concerns have risen regarding not only the drastic changes in patients' appearance but also the safety of the procedure. Fat tissue is known to act as a legitimate endocrine organ (5), being the primary depository for triglycerides, which classically relate to atherosclerosis and insulin resistance (6, 7). Recent work has linked lipid metabolism in adipocytes to the maintenance of low levels of systemic inflammation through a series of mediators (8-10). Scientific evidence (11) revealed an increase in the percentage of obese people in our country, as well as a considerable proportion of overweight people. This study also investigates the relationship between the prevalence of diabetes and hypertension. The classic association between body mass index and common metabolic diseases has led to investigations focused on several factors involved in this relationship, along with research work directed at the treatments available. The discovery of leptin in the 1990s (12) highlights the regulatory properties of the adipose tissue, whereas recent studies (5, 13) have established a link with the synthesis of other factors. In this study, we aimed to perform a review of literatures that discuss the current state-of-the-art of scientific research, in which we organized published works in a didactic manner in order to facilitate better understanding, and promote the safety and efficacy of liposuction.


Subject(s)
Humans , History, 21st Century , Surgery, Plastic , Triglycerides , Lipectomy , Adipose Tissue , Cholesterol , Risk Factors , Interleukins , Tumor Necrosis Factor-alpha , Review , Leptin , Evaluation Study , Diabetes Mellitus , Hypertension , Surgery, Plastic/methods , Triglycerides/analysis , Triglycerides/metabolism , Lipectomy/methods , Lipectomy/statistics & numerical data , Adipose Tissue/metabolism , Adipose Tissue/pathology , Cholesterol/metabolism , Interleukins/analysis , Interleukins/metabolism , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/metabolism , Leptin/metabolism , Diabetes Mellitus/prevention & control , Hypertension/prevention & control
13.
Rev. Col. Bras. Cir ; 41(2): 122-127, Mar-Apr/2014. tab, graf
Article in English | LILACS | ID: lil-711823

ABSTRACT

OBJECTIVE: To elucidate the role of the spleen and splenic allograft in lipid control and evaluate its effect on the lipid profile of rats. METHOD: 32 male Wistar rats were randomly assigned into four groups: control group (1), total splenectomy group (2), splenectomy and implantation of allograft group (3) and double spleen group (4). Each group was subdivided into two subgroups: A and B, based on the death of the animals after 30 or 120 days of monitoring. The procedures in groups 2, 3 and 4 were made simultaneously, and splenectomized animals, groups 2 and 3 were donors, respectively, for the animals of groups 3 and 4. In group 4 the spleen was preserved and the animals received implants from the spleens of rats from group 3. The regeneration of splenic tissue was evaluated by macroscopic and microscopic analyzes of the grafts and own spleens, as well as with measurements of VLDL, HDL, LDL, total cholesterol and triglycerides. RESULTS: after 120 days, Group 4 showed levels of total cholesterol and LDL lower than the other groups. Group 1 had higher levels of lipids. CONCLUSION: The technique of double spleen was effective in the control of lipid metabolism, corroborating the function of the spleen as a reserve of lipids. .


OBJETIVO: Este estudo objetiva elucidar o papel do baço e do aloenxerto esplênico no controle lipídico e avaliar seu efeito no lipidograma de ratos. MÉTODO: Foram distribuídos aleatoriamente 32 ratos machos da linhagem Wistar em quatro grupos: grupo controle (1), grupo esplenectomia total (2), grupo esplenectomia e implante de aloenxerto (3) e grupo baço duplo (4). Cada grupo foi subdividido em dois subgrupos: A e B, com base na morte dos animais após 30 ou 120 dias de acompanhamento. Os procedimentos nos animais dos grupos 2, 3 e 4 foram feitos simultaneamente, sendo que os animais esplenectomizados, grupos 2 e 3, foram doadores, respectivamente, para os animais dos grupos 3 e 4. No grupo 4 preservou-se o baço dos animais e implantou-se outro baço oriundo dos ratos do grupo 3. A regeneração do tecido esplênico foi avaliada por análises macro e microscópicas dos enxertos e dos baço próprios, bem como dosagens de VLDL, HDL, LDL, colesterol total e triglicérides. RESULTADOS: O Grupo 4 apresentou, após 120 dias, níveis de LDL e colesterol total inferiores aos demais grupos. O Grupo 1 apresentou os níveis de lipidograma mais elevados. CONCLUSÃO: A técnica do baço duplo foi eficaz no controle do metabolismo lipídico, comprovando a função do baço como reserva de lipídios. .


Subject(s)
Animals , Male , Rats , Allografts/immunology , Allografts/metabolism , Cholesterol/metabolism , Spleen/immunology , Spleen/metabolism , Triglycerides/metabolism , Random Allocation , Rats, Wistar , Splenectomy , Spleen/transplantation
14.
Botucatu; s.n; 2014. 46 p. ilus, graf.
Thesis in Portuguese | LILACS | ID: lil-772886

ABSTRACT

Objetivo: Avaliar o crescimento neonatal dos descendentes de ratas espontaneamente hipertensas (SHR) submetidas a exercício em esteira motorizada. Metodologia: Ratas SHR e Wystar Kyoto (WKY) foram distribuídas em: sedentárias (SHR e WKY), exercitadas durante a prenhez (SHR EXP e WKY EXP) e exercitadas previamente - antes e durante a prenhez (SHR EXPP e WKY EXPP). Durante a prenhez, pesos corpóreos, glicemia e nível de lactato e triglicérides e pressão arterial foram determinados. No 10º dia de vida pós-natal, peso, glicemia e comprimento corporal e cranial dos filhotes e triglicéride hepático foram analisados. Resultados: Não houve diferença no peso e lactato durante a prenhez e no número de filhotes entre os grupos. O grupo WKE EXPP apresentou maior pressão arterial comparado aos grupos WKY EXP E WKY. SHR EXPP e WKY EXPP apresentaram maior nível de triglicéride que os grupos exercitados na prenhez e sedentários. SHR EXPP apresentou menor glicemia que os SHR EXP e SHR. Não houve diferença nos parâmetros dos filhotes, mas o comprimento corpóreo foi maior nos grupos WKY EXPP e SHR EXPP. Conclusão: O exercício prévio foi exaustivo para a linhagem WKY. O exercício durante a prenhez não foi prejudicial para as ratas SHR e beneficiou o comprimento corpóreo dos filhotes...


Purpose: To evaluate the neonatal growth of the offspring of spontaneously hypertensive rats (SHR) subjected to treadmill exercise. Methods: SHR and Wystar Kyoto (WKY) rats were distributed into: sedentary group (SHR and WKY), exercised during pregnancy (SHR EXP and WKY EXP) and exercised previously and during pregnancy (SHR EXPP and WKY EXPP). During pregnancy, body weight, blood glucose, lactate and triglycerides levels and blood pressure were determined. At 10th day of life, body weight, blood glucose, and body and cranial length and hepatic triglycerides were analyzed. Results: There was no difference in body weight and lactate level during pregnancy, and number of pups among groups. The WKY EXPP group presented higher blood pressure than WKY and WKY EXP groups. SHR EXPP and WKY EXPP showed higher triglyceride level compared to groups trained in pregnancy and sedentary. SHR EXPP showed lower blood glucose than SHR and SHR EXP. There was no difference in the parameters of the newborns. In addition, body length was higher in WKY EXPP and SHR EXPP groups. Conclusion: The previous exercise was exhausting for the WKY strain. Exercise during pregnancy is not harmful to SHR rats and benefited the body length of offspring...


Subject(s)
Animals , Female , Pregnancy , Embryonic Development , Hypertension/physiopathology , Physical Exertion , Pregnancy, Animal , Lactic Acid/metabolism , Blood Glucose/physiology , Body Weight/physiology , Arterial Pressure/physiology , Triglycerides/metabolism
15.
Botucatu; s.n; 2014. 46 p. ilus, graf.
Thesis in Portuguese | LILACS | ID: lil-772895

ABSTRACT

Objetivo: Avaliar o crescimento neonatal dos descendentes de ratas espontaneamente hipertensas (SHR) submetidas a exercício em esteira motorizada. Metodologia: Ratas SHR e Wystar Kyoto (WKY) foram distribuídas em: sedentárias (SHR e WKY), exercitadas durante a prenhez (SHR EXP e WKY EXP) e exercitadas previamente - antes e durante a prenhez (SHR EXPP e WKY EXPP). Durante a prenhez, pesos corpóreos, glicemia e nível de lactato e triglicérides e pressão arterial foram determinados. No 10º dia de vida pós-natal, peso, glicemia e comprimento corporal e cranial dos filhotes e triglicéride hepático foram analisados. Resultados: Não houve diferença no peso e lactato durante a prenhez e no número de filhotes entre os grupos. O grupo WKE EXPP apresentou maior pressão arterial comparado aos grupos WKY EXP E WKY. SHR EXPP e WKY EXPP apresentaram maior nível de triglicéride que os grupos exercitados na prenhez e sedentários. SHR EXPP apresentou menor glicemia que os SHR EXP e SHR. Não houve diferença nos parâmetros dos filhotes, mas o comprimento corpóreo foi maior nos grupos WKY EXPP e SHR EXPP. Conclusão: O exercício prévio foi exaustivo para a linhagem WKY. O exercício durante a prenhez não foi prejudicial para as ratas SHR e beneficiou o comprimento corpóreo dos filhotes...


Subject(s)
Animals , Female , Pregnancy , Embryonic Development , Hypertension/physiopathology , Physical Exertion , Pregnancy, Animal , Lactic Acid/metabolism , Blood Glucose/physiology , Body Weight/physiology , Arterial Pressure/physiology , Triglycerides/metabolism
16.
Rev. Inst. Nac. Hig ; 44(1): 7-14, jun. 2013. graf, tab
Article in Spanish | LILACS, LIVECS | ID: lil-740427

ABSTRACT

Las leguminosas constituyen un componente importante de la dieta regular del venezolano. Algunos estudios han demostrado que los granos de varias leguminosas tienen un efecto hipocolesterolémico. En este estudio se evaluó el efecto del consumo de frijol blanco Vigna unguiculata con y sin cáscara sobre los lípidos plasmáticas en ratas hipercolesterolémicas. Treinta ratas machos adultas, cepa Sprague Dawley, fueron estudiadas en dos etapas. Una primera de tres semanas en la que mediante manipulación dietética, se transformaron ratas normales en hipercolesterolémicas. En la segunda etapa se diseñaron 4 grupos, un control normocolesterolémico sin dieta experimental, un hipercolesterolémico sin dieta experimental, un hipercolesterolémico alimentado con frijol con cáscara y uno hipercolesterolémico alimentado con frijol sin cáscara durante tres semanas. Las dietas con frijol blanco Vigna unguiculata produjeron una disminución significativa de colesterol total y triglicéridos de un 35.01% y 39.48% respectivamente, en comparación con el grupo hipercolesterolémico sin frijol. Para la fracción del colesterol-LDL la disminución fue de 59%, sin encontrarse diferencias significativas entre los grupos alimentados con frijol con y sin cáscara. Un hallazgo interesante fue el incremento significativo del colesterol-HDL de 29.66% en el grupo alimentado con frijol con cáscara, lo cual es un factor de prevención para la aparición de Enfermedades Cardiovasculares. Los resultados de este estudio señalan que el consumo de frijol blanco con o sin cáscara tuvo efecto beneficioso en el perfil lipídico, en este modelo experimental. En estudios futuros podría considerarse su uso en la dietoterapia de las hiperlipidemias.


Legumes are important components of Venezuelan diet. Several studies have shown that grains of legumes have a hypocholesterolemic effect. This study evaluated the effect of consumption of white beans Vigna unguiculata with and without hull on plasma lipids in hypercholesterolemic rats. Thirty adult male Sprague-Dawley rats, were studied in two stages. The first of three weeks, by means of dietary manipulation, normal rats became hypercholesterolemic. In the second stage, 4 groups were designed, one normocholesterolemic control without experimental diet, one hypercholesterolemic without experimental diet, one hypercholesterolemic fed with bean with hull and one hypercholesterolemic fed with bean without hull for three weeks. Diets with white beans Vigna unguiculata produced a significant decrease in total cholesterol and triglycerides of 35.01% and 39.48% respectively, compared with the hypercholesterolemic group without beans. The fraction of LDL-cholesterol showed a reduction of 59%, without significant differences between the groups fed with beans with and without hull. An interesting finding was the significant increase of HDL-cholesterol of 29.66% in the group fed with bean with hull, which is a preventive factor for cardiovascular diseases. The results of this study indicate that consumption of white beans with or without hull had beneficial effect on lipid profile, in this experimental model. In future studies it could be considered for using in diet therapy of human hyperlipidemia.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Rats , Triglycerides/metabolism , Dietary Fiber/analysis , Cholesterol/analysis , Fabaceae/classification , Rats , Public Health , Hypercholesterolemia , Lipids
17.
Rev. argent. microbiol ; 45(1): 3-12, mar. 2013. graf, tab
Article in English | LILACS | ID: lil-672048

ABSTRACT

In order to isolate novel organic solvent-tolerant (OST) lipases, a metagenomic library was built using DNA derived from a temperate forest soil sample. A two-step activity-based screening allowed the isolation of a lipolytic clone active in the presence of organic solvents. Sequencing of the plasmid pRBest recovered from the positive clone revealed the presence of a putative lipase/esterase encoding gene. The deduced amino acid sequence (RBest1) contains the conserved lipolytic enzyme signature and is related to the previously described OST lipase from Lysinibacillus sphaericus 205y, which is the sole studied prokaryotic enzyme belonging to the 4.4 a/ß hydrolase subgroup (abH04.04). Both in vivo and in vitro studies of the substrate specificity of RBest1, using triacylglycerols or nitrophenyl-esters, respectively, revealed that the enzyme is highly specific for butyrate (C4) compounds, behaving as an esterase rather than a lipase. The RBest1 esterase was purified and biochemically characterized. The optimal esterase activity was observed at pH 6.5 and at temperatures ranging from 38 to 45 °C. Enzymatic activity, determined by hydrolysis of p-nitrophenyl esters, was found to be affected by the presence of different miscible and non-miscible organic solvents, and salts. Noteworthy, RBest1 remains significantly active at high ionic strength. These findings suggest that RBest1 possesses the ability of OST enzymes to molecular adaptation in the presence of organic compounds and resistance of halophilic proteins.


Con el fin de aislar nuevas variantes de lipasas tolerantes a solventes organicos (OST), se construyo una libreria metagenomica a partir de ADN obtenido de una muestra de suelo de bosque templado. A traves de un monitoreo en dos etapas, basado en la deteccion de actividades, se aislo un clon con actividad lipolitica en presencia de solventes organicos. La secuenciacion del plasmido pRBest recuperado del clon positivo revelo la presencia de un gen codificante de una hipotetica lipasa/esterasa. La secuencia deducida de amino acidos (RBest1) contiene los motivos conservados de enzimas lipoliticas y esta relacionada con la lipasa OST previamente descrita de Lysinibacillus sphaericus 205y, que es la unica enzima procariota estudiada perteneciente al subgrupo 4.4 de a/ß hidrolasas (abH4.04). Estudios in vivo e in vitro sobre la especificidad de sustratos de RBest1, utilizando triacil-gliceroles o p-nitrofenil-esteres, respectivamente, revelaron que la enzima es altamente especifica para compuestos butiricos (C4), comportandose como una esterasa y no como una lipasa. La esterasa RBest1 fue purificada y caracterizada bioquimicamente. La actividad optima de esterasa fue observada a pH 6,5 y las temperaturas optimas fueron entre 38 y 45 °C. Se establecio que la actividad enzimatica, determinada por hidrolisis de p-nitrofenil esteres, es afectada en presencia de diferentes solventes organicos miscibles y no miscibles, y tambien sales. Notoriamente, RBest1 permanece significativamente activa a elevadas fuerzas ionicas. Estos hallazgos sugieren que RBest1 posee la capacidad de las enzimas OST de la adaptacion molecular en presencia de compuestos organicos, asi como la resistencia de las proteinas halofilas.


Subject(s)
Esterases/isolation & purification , Lipase/isolation & purification , Metagenomics , Amino Acid Sequence , Bacillaceae/enzymology , Bacterial Proteins/chemistry , Butyrates/metabolism , Conserved Sequence , DNA , Esterases/classification , Germany , Hydrogen-Ion Concentration , Hydrolysis , Lipolysis , Lipase/classification , Molecular Sequence Data , Osmolar Concentration , Phylogeny , Recombinant Proteins/metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Soil Microbiology , Substrate Specificity , Salts/pharmacology , Solvents/pharmacology , Temperature , Trees , Triglycerides/metabolism
18.
J. pediatr. (Rio J.) ; 89(1): 56-63, jan.-fev. 2013. tab
Article in Portuguese | LILACS | ID: lil-668826

ABSTRACT

OBJETIVO: O presente estudo objetivou identificar a prevalência do fenótipo cintura hipertrigliceridêmica (CHT) e avaliar sua associação com alterações metabólicas em adolescentes de baixa condição econômica. MÉTODO: Estudo transversal com amostra probabilística de 1.076 adolescentes entre 11 e 17 anos, de ambos os sexos, estudantes de escolas públicas. Os participantes foram submetidos à avaliação antropométrica (peso, altura e circunferência da cintura) e à dosagem dos níveis de colesterol total, LDL-C, HDL-C, colesterol não HDL, triglicérides (TG) e glicemia de jejum. Foram obtidas informações referentes às condições econômicas das famílias dos participantes.O fenótipo CHT foi definido pela presença simultânea da circunferência da cintura aumentada (> percentil 90 por idade e sexo) e dos níveis séricos de triglicérides elevados (> 100 mg/dL). A análise de regressão logística foi utilizada para avaliação das associações de interesse. RESULTADOS: A prevalência do fenótipo CHT foi de 7,2% entre os adolescentes, sendo mais elevada na presença de obesidade (63,4%), do colesterol não HDL (16,6%) e do LDL-C (13,7%) altos. A análise bivariada indicou que, das variáveis metabólicas, apenas a glicemia não se associou ao fenótipo CHT. A análise multivariada, ajustada por sexo e idade, indicou que o fenótipo CHT se associou positivamente com o colesterol não HDL alto (odds ratio, 7,0; IC 95% 3,9-12,6) e com o HDL-C baixo (odds ratio, 2,7; IC 95%, 1,5-4,8). CONCLUSÕES: Este estudo mostrou que o fenótipo CHT se associou com um perfil lipídico aterogênico e sugere esse fenótipo como uma ferramenta de screening que pode ser utilizada para identificar adolescentes com alterações metabólicas.


OBJECTIVE: This study aimed to identify the prevalence of hypertriglyceridemic waist (HTW) phenotype, and to evaluate its association with metabolic abnormalities in adolescents of low socioeconomic status. METHOD: This was a cross-sectional study with a random sample of 1,076 adolescents between 11 and 17 years, of both genders, from public schools. The participants underwent anthropometric measurements (weight, height, and waist circumference), and levels of total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), non-HDL cholesterol triglyceride (TG), and fasting glucose were measured. Information regarding the socioeconomic status of the participants' families was obtained. The HTW phenotype was defined by the simultaneous presence of increased waist circumference (> 90th percentile for age and gender) and serum triglyceride levels (> 100 mg/dL). A logistic regression analysis was used to evaluate the associations of interest. RESULTS: The prevalence of HTW phenotype was 7.2% among the adolescents, being higher in the presence of obesity (63.4%) and high levels of non-HDL cholesterol (16.6%) and LDL-C (13.7%). The bivariate analysis indicated that, of the metabolic variables, only blood glucose was not associated with the HTW phenotype. Multivariate analysis adjusted for age and gender indicated that the HTW phenotype was positively associated with high non-HDL cholesterol (odds ratio: 7.0; 95% CI: 3.9-12.6) and low HDL-C levels (odds ratio: 2.7; 95% CI: 1.5-4.8). CONCLUSIONS: This study demonstrated that the HTW phenotype was associated with an atherogenic lipid profile, and this phenotype is suggested as a screening tool to identify adolescents with metabolic alterations.


Subject(s)
Adolescent , Child , Female , Humans , Male , Hypertriglyceridemia/epidemiology , Metabolic Syndrome/epidemiology , Obesity, Abdominal/epidemiology , Triglycerides/metabolism , Waist Circumference , Body Mass Index , Blood Glucose/analysis , Cross-Sectional Studies , Cholesterol/blood , Hypertriglyceridemia/diagnosis , Hypertriglyceridemia/metabolism , Lipoproteins, HDL/blood , Mass Screening , Metabolic Syndrome/genetics , Obesity, Abdominal/diagnosis , Phenotype , Prevalence , Risk Factors , Sex Factors , Socioeconomic Factors , Triglycerides/blood
20.
Clinical and Molecular Hepatology ; : 210-215, 2013.
Article in English | WPRIM | ID: wpr-202393

ABSTRACT

Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.


Subject(s)
Humans , Acetyl Coenzyme A/metabolism , Fatty Acids/metabolism , Fatty Liver/metabolism , Lipogenesis , Mitochondria/metabolism , Triglycerides/metabolism
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