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Article in English | WPRIM | ID: wpr-927639


OBJECTIVE@#This study aimed to investigate the effects of caprylic acid (C8:0) on lipid metabolism and inflammation, and examine the mechanisms underlying these effects in mice and cells.@*METHODS@#Fifty-six 6-week-old male C57BL/6J mice were randomly allocated to four groups fed a high-fat diet (HFD) without or with 2% C8:0, palmitic acid (C16:0) or eicosapentaenoic acid (EPA). RAW246.7 cells were randomly divided into five groups: normal, lipopolysaccharide (LPS), LPS+C8:0, LPS+EPA and LPS+cAMP. The serum lipid profiles, inflammatory biomolecules, and ABCA1 and JAK2/STAT3 mRNA and protein expression were measured.@*RESULTS@#C8:0 decreased TC and LDL-C, and increased the HDL-C/LDL-C ratio after injection of LPS. Without LPS, it decreased TC in mice ( P < 0.05). Moreover, C8:0 decreased the inflammatory response after LPS treatment in both mice and cells ( P < 0.05). Mechanistic investigations in C57BL/6J mouse aortas after injection of LPS indicated that C8:0 resulted in higher ABCA1 and JAK2/STAT3 expression than that with HFD, C16:0 and EPA, and resulted in lower TNF-α, NF-κB mRNA expression than that with HFD ( P < 0.05). In RAW 264.7 cells, C8:0 resulted in lower expression of pNF-κBP65 than that in the LPS group, and higher protein expression of ABCA1, p-JAK2 and p-STAT3 than that in the LPS and LPS+cAMP groups ( P < 0.05).@*CONCLUSION@#Our studies demonstrated that C8:0 may play an important role in lipid metabolism and the inflammatory response, and the mechanism may be associated with ABCA1 and the p-JAK2/p-STAT3 signaling pathway.

ATP Binding Cassette Transporter 1/immunology , Animals , Caprylates/chemistry , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Humans , Inflammation/metabolism , Janus Kinase 2/immunology , Lipid Metabolism/drug effects , Macrophages/immunology , Male , Mice , Mice, Inbred C57BL , STAT3 Transcription Factor/immunology , Signal Transduction
Acta Physiologica Sinica ; (6): 209-216, 2022.
Article in Chinese | WPRIM | ID: wpr-927596


Mounting evidence has shown that exercise exerts extensive beneficial effects, including preventing and protecting against chronic diseases, through improving metabolism and other mechanisms. Recent studies have shown that exercise preconditioning affords significant cardioprotective effects. However, whether exercise preconditioning improves high fat diet (HFD)-induced obesity and lipid metabolic disorder remains unknown. The study was aimed to explore the effects of exercise preconditioning on HFD-induced obesity and lipid metabolic disorder in mice. 4-week-old C57BL/6 mice were subjected to swimming or sedentary control for 3 months, and then were fed with normal diet (ND) or HFD for 4 more months. The results showed that the blood glucose was decreased, and the glucose tolerance and grip strength were increased in exercised mice after training. Exercise preconditioning failed to improve HFD-induced body weight gain, but improved HFD-induced glucose intolerance. Exercise preconditioning showed no significant effects on both exercise capacity and physical activity in ND- and HFD-fed mice. HFD feeding increased total cholesterol and low density lipoprotein (LDL) levels in circulation, promoted subcutaneous fat and epididymal fat accumulation in mice. Exercise preconditioning increased circulating high density lipoprotein (HDL) and decreased circulating LDL, without affecting the subcutaneous fat and epididymal fat in HFD-fed mice. HFD feeding increased liver weight and hepatic total cholesterol contents, and dysregulated the expressions of several mitochondria function-related proteins in mice. These abnormalities were partially reversed by exercise preconditioning. Together, these results suggest that exercise preconditioning can partially reverse the HFD-induced lipid metabolic disorder and hepatic dysfunction, and these beneficial effects of exercise sustain for a period of time, even after exercise is discontinued.

Animals , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Lipids , Liver , Mice , Mice, Inbred C57BL , Obesity
Rev. cuba. invest. bioméd ; 40(1): e839, ene.-mar. 2021. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1289452


Introducción: La litogénesis biliar, proceso de sobresaturación de colesterol en la bilis vesicular, es prevenible. Objetivo: Describir las nuevas evidencias biomoleculares de la litogénesis biliar de colesterol como base de la futura terapia preventiva de la litiasis vesicular. Método: Se realizó una revisión sistemática y crítica de las evidencias de impacto sobre la litogénesis biliar. Se consultaron artículos publicados entre 2015-2020 en las bases de datos PubMed, Medline, SciELO, LILACS y Elsevier. Resultados: Se recuperaron evidencias actuales de los mecanismos biomoleculares relacionados con las futuras terapias preventivas de la litiasis vesicular, propuestos como fundamentos teóricos. Conclusiones: La descripción actualizada de la litogénesis biliar de colesterol, con los nuevos conceptos biomoleculares incorporados, aporta a su comprensión el papel de los genes de receptores nucleares, la intervención de estos últimos y de los transportadores de la secreción biliar. Dirigida a médicos generales, cirujanos, gastroenterólogos y fisiólogos, la descripción actualizada de La litogénesis biliar impacta como nuevo paradigma con los conceptos biomoleculares que intervienen en pro de su prevención(AU)

Introduction: Biliary lithogenesis is a preventable process of cholesterol supersaturation in gallbladder bile. Objective: Describe the new biomolecular evidence of biliary cholesterol lithogenesis serving as a basis for future preventive therapy for gallbladder lithiasis. Methods: A systematic critical review was conducted of impact evidence about biliary lithogenesis. The papers consulted were published in the databases PubMed, Medline, SciELO, LILACS and Elsevier from 2015 to 2020. Results: Current evidence was retrieved of biomolecular mechanisms proposed as theoretical foundations for future preventive therapies for gallbladder lithiasis. Conclusions: Intended for general practitioners, surgeons, gastroenterologists and physiologists, the updated description of biliary lithogenesis including the role of nuclear receptors, biliary lipid transporters and the biological value of enterohepatic circulation in the integrity and functioning of the hepatobiliary system as regulators of the cholesterol mechanism, makes an impact as a new paradigm with the biomolecular concepts involved in biliary lithogenesis prevention(AU)

Humans , Biological Products , Cholesterol/metabolism , Enterohepatic Circulation , Gastroenterologists , Gallbladder , Urinary Bladder Calculi/prevention & control
Article in Chinese | WPRIM | ID: wpr-879094


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.

Animals , Biological Transport , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Hyperlipidemias/metabolism , Liver/metabolism , Rats , Rats, Sprague-Dawley , Triglycerides/metabolism
Med. infant ; 26(3): 287-295, sept. 2019. Tab, ilus
Article in Spanish | LILACS | ID: biblio-1025029


La Hipercolesterolemia Familiar (HF) es una enfermedad hereditaria frecuente que se caracteriza por niveles elevados de colesterol ligado a las lipoproteínas de baja densidad (C-LDL). El exceso de LDL se acumula en las arterias produciendo aterosclerosis prematura. El diagnóstico y tratamiento desde la infancia mejoran el pronóstico de la enfermedad. Existe subdiagnóstico de la HF lo que provoca muertes prematuras por enfermedad cardiovascular (ECV). Para mejorar el subdiagnóstico la Sociedad Argentina de Pediatría propuso en el año 2015 realizar tamizaje universal al ingreso escolar. Es relevante entonces que el pediatra pueda diagnosticar la hipercolesterolemia y diferenciar las hipercolesterolemias monogénicas o familiares, de las secundarias (AU)

Familial hypercholesterolemia (FH) is a common hereditary disease that is characterized by high cholesterol levels, linked to low-density lipoproteins (LDL). Excess LDL accumulates in the arteries leading to premature atherosclerosis. Early diagnosis and treatment since childhood improve the prognosis of the disease. FH is underdiagnosed resulting in premature death due to cardiovascular disease (CVD). To improve diagnosis, in 2015 the Argentine Society of Pediatrics proposed a universal screening program at school age. It is relevant, therefore, for the pediatrician to be able to diagnose hypercholesterolemia and differentiate monogenic or familial from secondary hypercholesterolemia (AU)

Humans , Child, Preschool , Child , Adolescent , Cardiovascular Diseases/prevention & control , Cholesterol/metabolism , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/physiopathology , Hyperlipoproteinemia Type II/genetics , Hyperlipoproteinemia Type II/therapy , Mass Screening , Diagnosis, Differential , Anticholesteremic Agents/therapeutic use
An. bras. dermatol ; 94(3): 341-343, May-June 2019. graf
Article in English | LILACS | ID: biblio-1011101


Abstract: CHILD syndrome (Congenital Hemidysplasia, Ichthyosiform erythroderma, Limb Defects) is a rare X-linked dominant disease. The authors report a 2-month-old patient presenting with typical features of CHILD syndrome that was treated with a topical solution containing cholesterol and lovastatin, with complete clearance of her CHILD nevus. The changes in skin lipid metabolism that explain the CHILD ichthyosiform nevus and their correction through topical application of cholesterol and lovastatin are discussed.

Humans , Female , Infant , Abnormalities, Multiple/drug therapy , Lovastatin/administration & dosage , Cholesterol/metabolism , Ichthyosiform Erythroderma, Congenital/drug therapy , Limb Deformities, Congenital/drug therapy , Genetic Diseases, X-Linked/drug therapy , Anticholesteremic Agents/administration & dosage , Abnormalities, Multiple/genetics , Cholesterol/biosynthesis , Administration, Topical , Ichthyosiform Erythroderma, Congenital/genetics , Limb Deformities, Congenital/genetics , Genetic Diseases, X-Linked/genetics , Metabolic Diseases/genetics
Braz. j. microbiol ; 48(4): 730-739, Oct.-Dec. 2017. tab, graf
Article in English | LILACS | ID: biblio-889160


ABSTRACT Objective To screen for and characterize lactic acid bacteria strains with the ability to produce fermented milk and reduce cholesterol levels. Methods The strains were isolated from traditional fermented milk in China. In vitro and in vivo evaluation of cholesterol-reduction were used to identify and verify strains of interest. Characteristics were analyzed using spectrophotometry and plate counting assays. Results The isolate HLX37 consistently produced fermented milk with strong cholesterol-reducing properties was identified as Lactobacillus plantarum (accession number: KR105940) and was thus selected for further study. The cholesterol reduction by strain HLX37 was 45.84%. The isolates were acid-tolerant at pH 2.5 and bile-tolerant at 0.5% (w/v) in simulated gastric juice (pH 2.5) for 2 h and in simulated intestinal fluid (pH 8.0) for 3 h. The auto-aggregation rate increased to 87.74% after 24 h, while the co-aggregation with Escherichia coli DH5 was 27.76%. Strain HLX37 was intrinsically resistant to antibiotics such as penicillin, tobramycin, kanamycin, streptomycin, vancomycin and amikacin. Compared with rats in the model hyperlipidemia group, the total cholesterol content in the serum and the liver as well as the atherogenic index of rats in the viable fermented milk group significantly decreased by 23.33%, 32.37% and 40.23%, respectively. Fewer fat vacuoles and other lesions in liver tissue were present in both the inactivated and viable fermented milk groups compared to the model group. Conclusion These studies indicate that strain HLX37 of L. plantarum demonstrates probiotic potential, potential for use as a candidate for commercial use for promoting health.

Animals , Male , Cattle , Rats , Cholesterol/metabolism , Milk/microbiology , Lactobacillus plantarum/metabolism , Bile Acids and Salts/pharmacology , China , Rats, Sprague-Dawley , Probiotics/isolation & purification , Probiotics/metabolism , Cultured Milk Products/microbiology , Lactobacillus plantarum/isolation & purification , Lactobacillus plantarum/drug effects , Lactobacillus plantarum/genetics , Fermentation , Anti-Bacterial Agents/pharmacology
Rev. méd. Chile ; 145(9): 1099-1105, set. 2017. tab, graf
Article in Spanish | LILACS | ID: biblio-902593


Background: It is known that some nutrients play an important role in the development of cholelithiasis. Cholesterol is carried by micelles and vesicles in the bile. During the first stage of gallstone formation, cholesterol crystals derive from thermodynamically unstable vesicles. Aim: To determine the effect of a high fat diet on blood lipids and bile composition, and its implication in the formation of gallstones. Material and Methods: Two groups of 15 BALB/c mice each, coming from the same litter, were treated with a control or with a high-fat diet (64% fat and 0.14% cholesterol). After two months, the animals were sacrificed, blood and bile samples were obtained. Serum glucose and the corresponding lipid profiles were measured. In bile samples, cholesterol and phospholipid levels were analyzed, and cholesterol transporters (vesicles and micelles) were separated by gel filtration chromatography. Results: Treated animals showed an 87% increase in serum total cholesterol (p < 0.01), a 97% increase in HDL-cholesterol (p < 0.05) and a 140% increase in LDL-cholesterol (p < 0.05). No changes in serum triglycerides or glucose were observed. In bile, a 13% increase in biliary cholesterol (p < 0.05) was observed but no change in biliary phospholipids. Also, an increase in biliary vesicular transporters and an increase of cholesterol/phospholipid ratio in vesicular transporters were observed. Conclusions: A high fat diet may contribute to the formation of gallstones in our experimental model.

Animals , Male , Dietary Fats/metabolism , Gallstones/etiology , Gallstones/metabolism , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Phospholipids/metabolism , Bile/chemistry , Biological Transport , Dietary Fats/analysis , Cholesterol/analysis , Prospective Studies , Treatment Outcome , Models, Animal , Gallbladder/metabolism , Mice, Inbred BALB C
São Paulo; s.n; 2017. 79 p.
Thesis in Portuguese | LILACS | ID: biblio-875006


Introdução: Doenças cardiovasculares constituem importante causa de morte em todo mundo e a hipercolesterolemia está diretamente relacionada a elas. A dieta desempenha papel importante neste processo e alguns alimentos como o feijão caupi (Vigna unguiculata L. Walp), especialmente sua proteína, tem sido apontado com potencial capacidade de redução do colesterol plasmático. Os efeitos hipocolesterolêmicos já observados indicaram o uso da proteína do feijão caupi, ou dos seus peptídeos, como ingrediente funcional de alimentos para a promoção da saúde e a redução do risco de doenças. Entretanto, as consequências da digestão gastrointestinal na absorção destes peptídeos são claramente complexas tornando essenciais estudos in vitro e in vivo para avaliar a sua bioacessibilidade e sua resistência à degradação gastrointestinal, além da disponibilidade e real eficácia destes peptídeos. Objetivo: Analisar a biodisponibilidade de peptídeos e avaliar parâmetros ligados ao metabolismo do colesterol em modelos animais após ingestão de isolado proteico de feijão caupi. Métodos: A farinha de feijão caupi foi desengordurada e sua proteína isolada. O isolado proteico foi submetido a métodos de hidrólise in vitro, para verificação das frações peptídicas formadas e inferência sobre a capacidade de ligação à albumina. Dois experimentos in vivo foram conduzidos. No primeiro, o isolado proteico do feijão caupi foi administrado a ratos e a concentração dos peptídeos monitorada no sangue, por 2 horas. O experimento in vivo 2 consistiu na alimentação de hamsters com dietas normo (N) - e hipercolesterolêmicas por 21 dias, contendo a proteína do feijão caupi como única proteína da ração (I), comparada ao controle de caseína (H). Neste experimento foram analisados no plasma: colesterol total (CT) e frações (LDLc, VLDLc e HDLc), triglicerídeos (TG) e peptídeos; nas fezes: colesterol total (CF) e ácidos biliares (AB); no fígado: colesterol (CH) e lipídeos totais (LH), HMGCR (atividade enzimática e expressão) e expressão de SREBP2, LDLR, ABCA1, ABCG1, ABCG5, ABCG8, LXRa e AMPK. Resultados: Os peptídeos identificados a partir da hidrólise proteica do feijão caupi, ou a partir do plasma dos animais estudados não evidenciaram similaridades entre os experimentos ou corresponderam a sequências previamente identificadas para o feijão caupi a partir de banco de dados. CT, VLDLc, HDLc, TG, CH dos hamsters foram maiores nos grupos H e I quando comparado ao N; LDLc foi maior para I comparado aos demais; LH foi maior em H comparado a N, sendo que I não diferiu dos demais; CF foi maior para I comparado a N, sendo que H não diferiu dos demais. A expressão de ABCA1 foi maior para I em relação aos demais; LXRa foi maior para I em relação a H, mas N não diferiu dos demais; SREBP2 foi menor em H em comparação aos demais; HMGCR foi mais expressa em N em comparação aos demais, ao passo que a atividade desta enzima foi maior em I quando comparado a N, sendo que H não diferiu dos demais. Não houve diferença entre os grupos quanto a AB ou expressão de ABCG8 ou AMPK. Não foram obtidos resultados de expressão para LDLR, ABCG1 e ABCG5. Conclusão: Apesar de pesquisas anteriores a este trabalho terem evidenciado a capacidade do isolado proteico do feijão caupi em inibir a atividade da HMGCR, inibir a solubilização micelar ou melhorar o perfil de lipídeos plasmáticos, no trabalho atual esta matéria prima não mostrou atuação positiva quanto ao metabolismo do colesterol de hamsters nas condições experimentais utilizadas. Os fragmentos indicados como peptídeos obtidos a partir da hidrólise proteica do feijão caupi, ou do plasma dos animais estudados não corresponderam a peptídeos com comprovada, ou até mesmo, com indicação de bioatividade

Introduction: Cardiovascular diseases are important cause of death worldwide and hypercholesterolemia is directly related to them. Diet plays an important role in this process and some foods such as cowpea (Vigna unguiculata L. Walp), especially its protein, have been shown to have a potential for reducing plasma cholesterol. The hypocholesterolemic effects already observed indicated the use of cowpea protein, or its peptides, as a functional food ingredient for health promotion and reduction of disease risk. However, the consequences of gastrointestinal digestion on the absorption of these peptides are clearly complex, making in vitro and in vivo studies essential to assess their bioaccessibility and resistance to gastrointestinal degradation, as well as the availability and actual efficacy of these peptides. Objectives: To analyze the bioavailability of peptides and evaluate parameters related to cholesterol metabolism in animal models after ingestion of protein isolate of cowpea. Methods: Cowpea flour was defatted and its protein isolated. The protein isolate was subjected to in vitro hydrolysis methods to verify the formed peptide fractions and inference about albumin binding ability. Two in vivo experiments were conducted. In the first, the cowpea protein isolate was administered to rats and the concentration of the peptides monitored in the blood for 2 hours. The in vivo experiment 2 consisted of feeding hamsters with normal (N) - and hypercholesterolemic diets for 21 days, containing the cowpea protein as the sole dietary protein (I), compared to casein control (H). In this experiment were analyzed in the plasma: total cholesterol (TC) and fractions (LDLc, VLDLc and HDLc), triglycerides (TG) and peptides; In feces: total cholesterol (CF) and bile acids (AB); In the liver: cholesterol (CH) and total lipids (LH), HMGCR (enzymatic activity and expression) and expression of SREBP2, LDLR, ABCA1, ABCG1, ABCG5, ABCG8, LXRa and AMPK. XX. Results: The peptides identified from the protein hydrolysis of cowpea or from the plasma of the animals studied did not show similarities among the experiments or correspond to sequences previously identified for the cowpea from the database. CT, VLDLc, HDLc, TG, CH of hamsters were higher in groups H and I when compared to N; LDLc was higher for I compared to the others; LH was higher in H compared to N, and I did not differ from the others; CF was higher for I compared to N, and H did not differ from the others. The expression of ABCA1 was higher for I than the others; LXRa was higher for I than H, but N did not differ from the others; SREBP2 was lower in H compared to the others; HMGCR was more expressed in N compared to the others, whereas the activity of this enzyme was higher in I when compared to N, and H did not differ from the others. There was no difference between groups regarding AB or expression of ABCG8 or AMPK. No expression results were obtained for LDLR, ABCG1 and ABCG5. Conclusion: Although previous research to this work evidenced the ability of the cowpea protein isolate to inhibit HMGCR activity, inhibit micellar solubilization or improve the plasma lipid profile, in the current work this raw material did not show a positive cholesterol metabolism of hamsters under the experimental conditions used. The fragments indicated as peptides obtained from the protein hydrolysis of cowpea beans, or from the plasma of the animals studied did not correspond to peptides with proven, or even, with indication of bioactivity

Animals , Biological Availability , Cholesterol/metabolism , Fabaceae , Peptides/blood , Vigna , Eating , Hypercholesterolemia , Models, Animal
São Paulo; s.n; 2017. 83 p.
Thesis in Portuguese | LILACS | ID: biblio-875688


Introdução: As proteínas alimentares são fontes de peptídeos atuantes em vários processos metabólicos. Existem evidências de que a proteína do feijão caupi (Vigna unguiculata L. Walp) é capaz de reduzir o colesterol em hamsters e em humanos, porém, a permeabilidade após a digestão, o mecanismo de ação e a evidência direta da participação de peptídeos no metabolismo colesterol não são claros. Objetivo: Investigar a permeabilidade intestinal e avaliar o efeito nas vias luminal e endógena do metabolismo do colesterol de peptídeos provenientes de feijão caupi (Vigna unguiculata L. Walp). Metodologia: A permeabilidade dos peptídeos provenientes do caupi produzidos por hidrólise enzimática foi testada em linhagens de células Caco-2 usando placas Transwell®. Para investigar o efeito na via luminal, três peptídeos identificados na fração 3 kDa do hidrolisado (LLNPDDEQL; FFFGQDGGSKGEE e LNL) foram testados na solubilização de colesterol e fosfatidilcolina, no tamanho das micelas de colesterol e interação com ácidos biliares in vitro. Para verificar o efeito no metabolismo endógeno, linhagens de células HepG2 foram incubadas com peptídeos sintéticos (MELNAVSVVHS e MELNAVSVVSH) identificados como resultado do ensaio de permeação nas células Caco-2. A expressão de RNAm dos transportadores de colesterol NPC1L1, ABCA1 e ABCG1 foi realizada nas células Caco-2 e a expressão de HMGCR, SREBP2, LDLR, LXR, AMPK1 foi avaliada nas células HepG2. Resultados: A exposição das células Caco-2 à fração 3 kDa do hidrolisado (2,5 e 5 mg/mL) aumentou a expressão de ABCG1 nos tempos 6 h e 12 h. O níveis de RNAm dos genes SREBP2, HMGCR e LDLR reduziram nas HepG2 após 24h do tratamento com o peptídeo MELNAVSVVHS (50 M e 100 M). A fração 3 kDa do hidrolisado e os peptídeos LLNPDDEQL; FFFGQDGGSKGEE e LNL foram capazes de reduzir a solubilidade do colesterol micelar in vitro em no máximo 42 por cento , bem como, provocaram mudanças estruturais ao interagirem com a fosfatidilcolina, com destaque ao peptídeo LNL (50 por cento de ligação). O peptídeo LNL foi o único capaz de promover a precipitação do colesterol em forma de cristais devido à interação com os ácidos biliares. Conclusões: A fração 3 kDa do hidrolisado e todos os peptídeos testados foram capazes de insolubilizar o colesterol in vitro. Constata-se que o mecanismo de competição pelo espaço intramicelar com o colesterol se dá pela interação com os componentes micelares e não diretamente com o colesterol. O peptídeo do feijão caupi MELNAVSVVHS foi permeável e foi capaz de reduzir a expressão do fator de transcrição SREBP2 (consequentemente reduzindo HMGCR e LDLR)

Introduction: Food proteins are sources of peptides acting in sevral metabolic processes. There is evidence that cowpea (Vigna unguiculata L. Walp) protein is able to lower cholesterol levels in hamsters and humans, but its permeability after digestion, mechanism of action and direct evidences of peptide participation in cholesterol metabolism are not clear. Objective: To investigate the intestinal permeability and to evaluate the effect on the luminal and endogenous cholesterol metabolism pathways of peptides from cowpea (Vigna unguiculata L. Walp). Methods: The permeability of the cowpea peptides produced by enzymatic hydrolysis was tested on Caco-2 cell lines using Transwell® plates. To investigate the effect on the luminal pathway, three peptides identified in the 3 kDa hydrolyzate fraction (LLNPDDEQL; FFFGQDGGSKGEE and LNL) were tested for in vitro cholesterol and phosphatidylcholine solubilization, cholesterol micelle size changing and interaction with bile acids. To verify the effect on endogenous metabolism, HepG2 cell lines were incubated with synthetic peptides (MELNAVSVVHS or MELNAVSVVSH) identified as a result of the permeation assay on Caco-2 cells. The mRNA expression of the cholesterol transporters NPC1L1, ABCA1 and ABCG1 was performed on Caco-2 cells and the expression of HMGCR, SREBP2, LDLR, LXR, AMPK1 was evaluated in HepG2 cells. Results: Exposure of Caco-2 cells to the 3 kDa hydrolyzate fraction (2.5 and 5 mg/mL) increased ABCG1 expression at 6 h and 12 h times. The mRNA levels of the SREBP2, HMGCR and LDLR genes were reduced in HepG2 after 24h of treatment with the MELNAVSVVHS peptide (50 M and 100 M). The 3 kDa of the hydrolyzate fraction and the peptides LLNPDDEQL; FFFGQDGGSKGEE and LNL were able to reduce the solubility of micellar cholesterol in vitro in a maximum of 42 per cent , as well as, caused structural changes when interacting with phosphatidylcholine, with emphasis on the LNL peptide (50 per cent of binding). The LNL peptide alone was able to promote cholesterol precipitation in the form of crystals due to interaction with bile acids. Conclusions: The 3 kDa hydrolysate fraction and all peptides tested were able to insolubilize cholesterol in vitro. It was observed that the mechanism of competition for the intramicellar space with cholesterol is given by the interaction with the micellar components and not directly with the cholesterol. The MELNAVSVVHS cowpea peptide was permeable and was able to reduce the expression of the SREBP2 transcription factor (thereby reducing HMGCR and LDLR)

Cholesterol/metabolism , Fabaceae , Intestines , Lipid Metabolism , Peptides , Hydrolysis , Permeability
Arch. latinoam. nutr ; 66(4): 279-286, dic. 2016. ilus
Article in Spanish | LILACS, LIVECS | ID: biblio-838454


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)

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


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.

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
Braz. j. biol ; 76(1): 59-65, Feb. 2016. graf
Article in English | LILACS | ID: lil-774508


Abstract Multiple myeloma (MM) is a B cell bone marrow neoplasia characterized by inflammation with an intense secretion of growth factors that promote tumor growth, cell survival, migration and invasion. The aim of this study was to evaluate the effects of pravastatin, a drug used to reduce cholesterol, in a MM cell line.Cell cycle and viability were determinate by Trypan Blue and Propidium Iodide. IL6, VEGF, bFGF and TGFβ were quantified by ELISA and qRT-PCR including here de HMG CoA reductase. It was observed reduction of cell viability, increase of cells in G0/G1 phase of the cell cycle and reducing the factors VEGF and bFGF without influence on 3-Methyl-Glutaryl Coenzyme A reductase expression.The results demonstrated that pravastatin induces cell cycle arrest in G0/G1 and decreased production of growth factors in Multiple Myeloma cell line.

Resumo O Mieloma Múltiplo é uma neoplasia de linfócitos B da medula óssea, caracterizada por inflamação com uma intensa secreção de fatores de crescimento que promovem o aumento do volume do tumor, sobrevivência celular, migração e invasão. O objetivo deste estudo foi avaliar os efeitos da pravastatina, uma droga usada para reduzir o colesterol, em um linhagem de MM. O ciclo celular e viabilidade foram determinadas por Trypan Blue e iodeto de propídio. IL6, VEGF, bFGF e TGF foram quantificadas por ELISA e qRT-PCR, incluindo aqui de HMG CoA redutase. Observou-se a redução da viabilidade das células, aumento de células na fase G0/G1 do ciclo celular e redução no VEGF e bFGF, sem influência na expressão da enzima 3-Metil-Glutaril Coenzima A redutase. Os resultados demonstraram que a pravastatina induz parada no ciclo celular em G0/G1 e diminuição da produção de fatores de crescimento em várias linhas de células de Mieloma.

Humans , Fibroblast Growth Factors/genetics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Multiple Myeloma/metabolism , Pravastatin/pharmacology , Vascular Endothelial Growth Factor A/genetics , Anticholesteremic Agents/pharmacology , Cell Line , Cell Cycle Checkpoints/drug effects , Cholesterol/metabolism , Fibroblast Growth Factors/metabolism , Vascular Endothelial Growth Factor A/metabolism
Braz. j. med. biol. res ; 49(11): e5562, 2016. tab, graf
Article in English | LILACS | ID: biblio-951654


The main purpose of this study was to investigate bifidobacteria flora in fecal samples from children with rotavirus infection and determine the significance of their selected probiotic properties for improvement of health status. Enzyme-linked immunosorbent assay was used to identify rotavirus antigen in fecal samples from 94 patients with gastroenteritis and from 30 without gastroenteritis. Bifidobacteria were identified by selective media, gram reaction, colony morphology, fructose-6-phosphate phosphoketolase enzyme activity and classical identification tests. Exopolysaccharide (EPS) production was identified by phenol-sulphuric acid method. The modified method was then used to identify the quantity of taurocholic and glycocholic acid deconjugation and cholesterol elimination of the strains. Thirty-five of the 94 fecal samples were found positive for rotavirus antigen (37.23%). Bifidobacteria were identified in 59 of the samples. The EPS production ranges were 29.56-102.21 mg/L. The cholesterol elimination rates ranged between 8.36-39.22%. Furthermore, a positive and strong correlation was determined between EPS production and the presence of cholesterol (r=0.984, P<0.001). The deconjugation rates for the sodium glycocholate group was higher than the sodium taurocholate group. Rotavirus (+) bifidobacteria strains had higher EPS production, deconjugation rate and cholesterol elimination compared to bifidobacteria strains isolated from children in the rotavirus (-) sample and without gastroenteritis. Significant differences were observed among groups in all parameters (P<0.05). Given the increased number of rotavirus cases in Turkey and worldwide, it is very important to add superior bifidobacteria in the diets of infected children to improve the intestinal and vital functions.

Humans , Child, Preschool , Polysaccharides, Bacterial/biosynthesis , Bifidobacterium/isolation & purification , Bile Acids and Salts/metabolism , Cholesterol/metabolism , Gastroenteritis/virology , Antigens, Viral/analysis , Rotavirus Infections/microbiology , Enzyme-Linked Immunosorbent Assay , Feces/virology
Int. j. cardiovasc. sci. (Impr.) ; 28(5): 400-408, set.-out. 2015. tab, graf
Article in Portuguese | LILACS | ID: lil-786806


Fundamentos: O consumo de alimentos funcionais (AF), como aveia e linhaça, representa estratégia segura e eficaz para reduzir o risco de doenças crônicas não transmissíveis (DCNT). Objetivo: Analisar o efeito da suplementação alimentar com farinha de linhaça marrom ou com aveia em flocos no índice de massa corporal (IMC), na circunferência da cintura (CC) e no perfil lipídico de idosos. Métodos: Estudo longitudinal controlado, randomizado, com duração de oito semanas, realizado com 60 indivíduos idosos (idade ≥60 anos), avaliados em três momentos: basal (T0), em quatro semanas (T1) e em oito semanas (T2) após o início do estudo. Peso, altura e CC foram mensurados e amostras de sangue coletadas. Os voluntários foram distribuídos aleatoriamente em grupo-controle (GC), grupo-linhaça (GL) e grupo-aveia (GA).Resultados: IMC e CC não se alteraram significativamente ao longo do estudo nos grupos. O GA mostrou reduçãode 18,4% nos níveis de colesterol total (CT) no plasma em relação ao GL ao final do período de estudo (p<0,05).O GA demonstrou ainda, em T2, valores 30,4% mais baixos de LDL colesterol do que os grupos GL e GC (p<0,05). Por outro lado, o GL apresentou elevação de 12,0% nos níveis de triglicerídeos de T0 para T2 (p<0,05). Conclusão: A suplementação com alimentos funcionais foi benéfica para redução do CT e do LDL colesterol.

Background: The consumption of functional foods (FF), as oat and linseed, is a safe and efficient strategy for reducing the risk of non-transmissible chronic diseases (NTCD). Objective: Analyzing the effect of food supplementation with brown linseed flour or oat in flakes on the body mass index (BMI), on the waist circumference (WC) and on the lipid profile of elderly.Methods: Longitudinal controlled, randomized study, with duration of eight weeks, made with 60 senior individuals (age > 60 years), evaluated at three moments: baseline (T0), four weeks (T1) and eight weeks (T2) after the study started. Weight, height and WCwere measured and blood samples were collected. Volunteers were randomly divided into control group (CG), linseed group (LG) and oat group (OG).Results: BMI and WC have not changed significantly throughout the study in any group. OG showed reduction of 18.4% in the total cholesterol (TC) levels in the plasma compared to LG in the end of the study period (p<0.05). OG showed also, at T2, values 30.4% lower for LDL cholesterol than LG and CG (p<0.05). On the other hand, LG showed increase of 12.0% in the triglycerides levels from T0 to T2 (p<0.05). Conclusion: The supplementation with functional foods was beneficial for reducing the TC and LDL cholesterol.

Humans , Male , Female , Middle Aged , Abdominal Circumference , Aged , Body Mass Index , Functional Food , Nutritional Status , Aging , Avena , Cholesterol/metabolism , Cholesterol/blood , Flax , Cholesterol, HDL/metabolism , Cholesterol, HDL/blood , Cholesterol, LDL/metabolism , Cholesterol, LDL/blood , Obesity/complications , Risk Factors
Rev. bras. oftalmol ; 74(5): 306-308, set.-out. 2015. ilus
Article in Portuguese | LILACS | ID: lil-757461


Este trabalho tem por objetivo relatar um caso de sínquise cintilante de câmara anterior em lactente sem causa elucidada. O paciente apresentou desvio no olhar desde o nascimento. Antecedentes pessoais e familiares sem anormalidades. Ao exame em OE: Esotropia constante, nistagmo horizontal, leucocoria e microftalmia, já em OD: sem anormalidades. Ultrassonografia (USG) em OE: redução do comprimento axial, retina aplicada e vítreo hiperecogênico. Aventaram-se hipóteses de persistência de vítreo primário hiperplásico, catarata congênita e retinoblastoma, e solicitou-se tomografia de crânio e cavidade orbitária (TC). Paciente retornou após 6 meses trazendo resultado da TC cuja única alteração evidenciada era OE com áreas hiperatenuantes e sem sinais de calcificação. Ao exame em OD: reflexo pupilar direto positivo e consensual negativo e em OE: hiperemia conjuntival, análise de reflexo pupilar, inviabilizada por presença de sínquises cintilantes de coloração ocre na câmara anterior, que não estava presente no exame inicial. Solicitou-se nova USG, evidenciando: ecos puntiformes na cavidade vítrea, sugerindo hemorragia, espessamento de hialoide posterior, retina aplicada e coroide com espessura aumentada. A sínquise cintilante ou “colesterolosis bulbi” é um processo degenerativo comumente secundário a trauma, inflamação ou hemorragia intraocular. Cursa com deposição de cristais de colesterol (provenientes do cristalino em degeneração ou do próprio vítreo) na cavidade vítrea, espaço sub-retiniano e, mais raramente, na câmara anterior. Sugerese que o fenômeno decorra de traumas, catarata de longa duração, hifema, glaucoma secundário ou descolamento de retina e mais raramente, de uveítes, neoplasias ou vasculopatias. Até o presente, não há relato na literatura de sínquise cintilante de câmara anterior envolvendo um lactente.

The propose of this article is presenting a case report of Synchisis scintillans of the anterior chamber in an infant patient without any elucidation. The patient’s initial complaint was “strabismus since birth”. There was not found any other personal or family abnormalities. On examination: OS: Esotropia maintained, horizontal nystagmus, microphthalmia and leukocoria. OD: no abnormalities. Ultrasonography (USG) OS: reduction of the axial length, retinal applied and hyperechoic vitreous. Raised hypotheses were persistence of hyperplastic primary vitreous, congenital cataract and retinoblastoma, and there was also requested cranial and orbital cavity tomography (TC). The patient returned after six months with TC showing as sole evidenced hyperattenuating areas without signs of calcification on OS. On examination: OD showing direct pupillary reflex positive and consensual pupillary reflex negative. OS: conjunctival hyperemia and analysis of pupillary reflex frustrated by the presence of sparkling colored ocher in the anterior chamber. We asked for a new USG, which showed: punctate echoes in the vitreous cavity, suggesting hemorrhage; thickening of the posterior hyaloids; choroid and retina were attached, both with increased thickness. The synchisis scintillans or “colesterolosis bulbi” is a degenerative process commonly secondary to trauma, inflammation or intraocular hemorrhage. Evolves with deposition of cholesterol crystals (from degeneration of the lens or vitreous itself) in the vitreous cavity, subretinal space and rarely, in the anterior chamber. There are evidences that the phenomenon could arise from severe trauma, long-term cataract, hyphema, glaucoma or retinal detachment and, even more rarely, uveitis, neoplasias or vascular disorders. Until this case, there was no report of Synchisis scintillans in the anterior chamber involving an infant.

Humans , Infant , Crystallization , Anterior Chamber/pathology , Cholesterol/metabolism , Eye Diseases/pathology
Arq. gastroenterol ; 52(3): 210-215, July-Sep. 2015. tab
Article in English | LILACS | ID: lil-762872


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.

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
Arq. bras. endocrinol. metab ; 58(8): 783-797, 11/2014. tab, graf
Article in English | LILACS | ID: lil-729785


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.

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 A/metabolism , Insulin/metabolism , Leptin/deficiency , Leptin/metabolism , Lipodystrophy/metabolism , Liver/metabolism , Syndrome , Serum Albumin/metabolism , Transaminases/metabolism , Triglycerides/metabolism
Rev. bras. cir. plást ; 29(3): 456-466, jul.-sep. 2014.
Article in English, Portuguese | LILACS | ID: biblio-748


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.

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
Rev. Col. Bras. Cir ; 41(2): 122-127, Mar-Apr/2014. tab, graf
Article in English | LILACS | ID: lil-711823


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. .

Animals , Male , Rats , Allografts/immunology , Allografts/metabolism , Cholesterol/metabolism , Spleen/immunology , Spleen/metabolism , Triglycerides/metabolism , Random Allocation , Rats, Wistar , Splenectomy , Spleen/transplantation