Caprylic Acid Improves Lipid Metabolism, Suppresses the Inflammatory Response and Activates the ABCA1/p-JAK2/p-STAT3 Signaling Pathway in C57BL/6J Mice and RAW264.7 Cells / 生物医学与环境科学（英文）

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.

Sex-differential effects of olanzapine vs. aripiprazole on glucose and lipid metabolism in first-episode schizophrenia

Abstract Objective To compare sex difference in metabolic effect of olanzapine versus aripiprazole on schizophrenia. Methods A twelve-week prospective open-label cohort study to compare four subgroups according to first-episode schizophrenia patients' type of drug usage and sex: female aripiprazole (n = 11), male aripiprazole (n = 11), female olanzapine (n = 10), and male olanzapine (n = 11) for body mass index, fasting serum triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting glucose. Results Aripiprazole may be associated with weight gain in female patients with low-baseline weight. Aripiprazole may have an adverse effect of weight and favorable effects of circulating glucose and lipid on female over male schizophrenia patients. The aripiprazole-induced changes in glucose and lipid may be independent of body fat storage, especially for female schizophrenia patients. Olanzapine may have adverse effects of weight, glucose and lipid profiles on female over male schizophrenic patients. Discussion Our findings fill the gap in knowledge and provide a sex-specific guidance to psychiatrist better tailoring treatment to individual sex-differential characteristics and a key clue to understand the sex-differential mechanism of antipsychotics-induced metabolic dysfunction.

Palmitic acid-induced lipotoxicity promotes a novel interplay between Akt-mTOR, IRS-1, and FFAR1 signaling in pancreatic ß-cells

BACKGROUND: Free fatty acid receptor 1 (FFAR1) is G-protein coupled receptor predominantly expressed in pancreatic ß-cells that is activated by a variety of free fatty acids (FFAs). Once activated, it promotes glucose-stimulated insulin secretion (GSIS). However, increased levels of FFAs lead to lipotoxicity, inducing loss of ß-cell function. FFAR1 plays a key role in the development of type 2 diabetes (T2D), and previous studies have indicated the importance of developing anti-diabetic therapies against FFAR1, although its role in the regulation of ß-cell function remains unclear. The present study investigated the role of FFAR1 under lipotoxic conditions using palmitic acid (PA). The rat insulinoma 1 clone 832/13 (INS-1 832/13) cell line was used as a model as it physiologically resembles native pancreatic ß-cells. Key players of the insulin signaling pathway, such as mTOR, Akt, IRS-1, and the insulin receptor (INSR1ß), were selected as candidates to be analyzed under lipotoxic conditions. RESULTS: We revealed that PA-induced lipotoxicity affected GSIS in INS-1 cells and negatively modulated the activity of both IRS-1 and Akt. Reduced phosphorylation of both IRS-1 S636/639 and Akt S473 was observed, in addition to decreased expression of both INSR1ß and FFAR1. Moreover, transient knockdown of FFAR1 led to a reduction in IRS-1 mRNA expression and an increase in INSR1ß; mRNA. Finally, PA affected localization of FFAR1 from the cytoplasm to the perinucleus. CONCLUSIONS: In conclusion, our study suggests a novel regulatory involvement of FFAR1 in crosstalk with mTOR-Akt and IRS-1 signaling in ß-cells under lipotoxic conditions.

Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice

BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/ oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.

Efectos adversos de finasteride: mitos y realidades. una revisión actualizada / Finasteride adverse effects: an update

Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

Protective Effects of Curcumin on Renal Oxidative Stress and Lipid Metabolism in a Rat Model of Type 2 Diabetic Nephropathy

PURPOSE: Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. MATERIALS AND METHODS: Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. RESULTS: Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. CONCLUSION: Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.

Single-nucleotide polymorphisms: a perspective of cardiovascular prevention / Polimorfismos de nucleotídeo único: uma perspectiva de prevenção cardiovascular

Summary Introduction: several studies have evaluated the utilization of lipid biomarkers in an attempt to correlate them with clinical cardiovascular events. Nevertheless, the investigation of clinical conditions under specific plasmatic levels of lipoproteins for long periods presents limitations due to inherent difficulties that are related to the follow-up of individuals throughout their lives. Better understanding of the clinical response and occasional resistance to the action of hypolipidemic drugs in several clinic scenarios is also necessary. Objectives: to determine the role of evaluation of single-nucleotide polymorphisms (SNPs) related to the metabolism of lipids, and its implications in different clinical scenarios. Methods: a search of the literature in English and Spanish languages was performed in Medline, Lilacs via Bireme, IBECS via Bireme, and Cochrane databases. The expected results included information regarding plasmatic lipid profile and SNPs, cardiovascular clinical outcomes and polymorphisms related to the effectiveness of statins in the treatment of hypercholesterolemia. Results: in order to perform this analysis, 19 studies were included from a total of 89 identified citations. The evaluation of the results suggests that low plasmatic levels of LDL-c are associated with a reduction in the risk of heart attacks, although this was not observed for the rise of plasmatic levels of HDL-c. Conclusion: polymorphisms in different populations and clinical perspectives may bring important contributions for a better understanding and adequacy of plasmatic lipoproteins aiming at reducing cardiovascular risk.

Resumo Introdução: muitos estudos tem avaliado a utilização de biomarcadores lipídicos na tentativa de correlacioná-los com eventos clínicos cardiovasculares. Contudo, a investigação de condições clínicas sob níveis plasmáticos específicos de lipoproteínas por longos períodos, apresenta limitações devido às dificuldades inerentes relacionadas ao acompanhamento de indivíduos ao longo de suas vidas. Adicionalmente, há a necessidade de melhor compreensão da resposta clínica e eventual resistência da ação de drogas hipolipemiantes em diversos cenários clínicos. Objetivos: determinar o papel da avaliação de polimorfismos de nucleotídeo único (SNPs) relacionadas com o metabolismo lipídico e suas implicações em diferentes cenários clínicos. Métodos: foi realizada uma pesquisa na literatura de língua inglesa e espanhola nas bases de dados Medline, Lilacas via Bireme, IBECS via Bireme e Cochrane. Os resultados esperados incluíam informações sobre o perfil lipídico plasmático e SNPs, desfechos clínicos cardiovasculares e polimorfismos relacionadas à efetividade de estatinas quanto ao tratamento da hipercolesterolemia. Resultados: para esta análise foram incluídos 19 estudos de um total de 89 citações identificadas. Os dados resultantes e avaliados sugerem que baixos níveis plasmáticos de LDL-c estão associados com redução do risco de infarto do miocárdio o que não foi observado para o aumento nos níveis plasmáticos de HDL-c. Conclusão: os polimorfismos em diferentes populações e perspectivas clínicas podem trazer importantes contribuições para a melhor compreensão e adequação de metas de lipoproteínas plasmáticas que visem a redução de risco cardiovascular.

Impact of vigorous exercise on serum levels of L-Carnitine in prisoners in Colombia / Impacto del ejercicio vigoroso sobre los niveles séricos de L-Carnitina en prisioneros de Colombia

Objective To assess the effect of a program of vigorous physical exercises on the serum concentration of free and total L-carnitine, in male inmates at a prison in Boyacá, Colombia. Methods Pre-post intervention population-based study. 44 male prisoners with overweight and/or obesity, from a jail in Boyacá, Colombia were randomly assigned into two groups: an intervention group and a control group. The intervention consisted in participating in a vigorous exercise program over twelve weeks. Anthropometric measures and levels of free and total L-carnitine were every four weeks. Results There were significant increases in serum levels of free and total L-carnitine in the intervention group compared to the control group. Concurrently, in this group there was a reduction in body mass index (BMI), while in the control group there were no changes. Conclusion In overweight and/or obese patients, the routine practice of vigorous exercise plus caloric restriction offers significant benefits in reducing body fat volumes through the mechanisms of energetic consumption of long chain fatty acids.(AU)

Objetivo Evaluar el efecto de un programa de ejercicio físico intenso sobre las concentraciones séricas de L-Carnitina libre y total, en varones recluidos en una prisión de Boyacá, Colombia. Métodos Estudio de intervención antes - después, de base poblacional. 44 internos con sobrepeso y/o obesidad, de una prisión en Boyacá, Colombia, fueron aleatoriamente asignados a dos grupos: Uno de intervención y uno de control. La intervención consistió en un programa de práctica sistemática de ejercicio intenso, durante doce semanas continuas. Cada cuatro semanas se realizaron mediciones antropométricas y se determinaron los niveles séricos de L-Carnitina libre y total. Resultados Hubo un incremento significativo en los niveles séricos de L-Carnitina libre y Total en el grupo de intervención, comparado con lo registrado en el grupo control; simultáneamente, en el grupo de intervención se registró disminución en el índice de masa corporal (IMC), mientras que en el grupo control no se registraron cambios. Conclusión En presencia de sobrepeso y/o obesidad, la práctica rutinaria de ejercicios físicos intensos además de la restricción calórica, ofrece significativos beneficios en la reducción del volumen de grasa corporal por el mecanismo de consumo energético de los ácidos grasos de cadena larga.(AU)

Fructo-oligosaccharide effects on serum cholesterol levels. An overview

PURPOSE: To address the effects of fructooligosaccharides (FOS) intake on serum cholesterol levels. METHODS: We performed a search for scientific articles in MEDLINE database from 1987 to 2014, using the following English keywords: fructooligosaccharides; fructooligosaccharides and cholesterol. A total of 493 articles were found. After careful selection and exclusion of duplicate articles 34 references were selected. Revised texts were divided into two topics: "FOS Metabolism" and "FOS effects on plasma cholesterol." RESULTS: The use of a FOS diet prevented some lipid disorders and lowered fatty acid synthase activity in the liver in insulin-resistant rats. There was also reduction in weight and total cholesterol in beagle dogs on a calorie-restricted diet enriched with short-chain FOS. Another study found that 2g FOS daily consumption increased significantly serum HDL cholesterol levels but did not ensure a significant reduction in levels of total cholesterol and triglycerides.. Patients with mild hypercholesterolemia receiving short-chain FOS 10.6g daily presented no statistically significant reduction in serum cholesterol levels. However, when FOS was offered to patients that changed their lifestyle, the reduction of LDL cholesterol and steatosis was higher. CONCLUSIONS: Fructooligosaccharides intake may have a beneficial effect on lipid metabolism and regulation of serum cholesterol levels in individuals that change their lifestyle. FOS supplementation use in diets may therefore be a strategy for lowering cholesterol. .

Evaluation of Nosocomial Infection Control Programs in health services / Avaliação dos Programas de Controle de Infecção Hospitalar em serviços de saúde / Evaluación de los Programas de Control de Infección Hospitalaria en servicios de salud

OBJECTIVES: to evaluate the Nosocomial Infection Control Programs in hospital institutions regarding structure and process indicators. METHOD: this is a descriptive, exploratory and quantitative study conducted in 2013. The study population comprised 13 Nosocomial Infection Control Programs of health services in a Brazilian city of the state of São Paulo. Public domain instruments available in the Manual of Evaluation Indicators of Nosocomial Infection Control Practices were used. RESULTS: The indicators with the highest average compliance were "Evaluation of the Structure of the Nosocomial Infection Control Programs" (75%) and "Evaluation of the Epidemiological Surveillance System of Nosocomial Infection" (82%) and those with the lowest mean compliance scores were "Evaluation of Operational Guidelines" (58.97%) and "Evaluation of Activities of Control and Prevention of Nosocomial Infection" (60.29%). CONCLUSION: The use of indicators identified that, despite having produced knowledge about prevention and control of nosocomial infections, there is still a large gap between the practice and the recommendations. .

OBJETIVOS: avaliar os Programas de Controle de Infecção Hospitalar nas instituições hospitalares, quanto aos indicadores de estrutura e processo. MÉTODO: trata-se de um estudo descritivo, exploratório e quantitativo, realizado em 2013. A população foi composta por 13 Programas de Controle de Infecção Hospitalar de serviços de saúde, de uma cidade brasileira do interior paulista. Foram utilizados instrumentos de domínio público, disponibilizados no Manual de Indicadores de Avaliação de Práticas de Controle de Infecção Hospitalar. RESULTADOS: os indicadores com maior média de conformidade foram "Avaliação da Estrutura dos Programas de Controle de Infecção Hospitalar" (75%) e "Avaliação do Sistema de Vigilância Epidemiológica de Infecção Hospitalar" (82%) e os com menores médias foram "Avaliação das Diretrizes Operacionais" (58,97%) e "Avaliação das Atividades de Controle e Prevenção de Infecção Hospitalar" (60,29%). CONCLUSÃO: o uso de indicadores identificou que, apesar do conhecimento produzido sobre ações de prevenção e controle de infecções hospitalares, ainda existe um grande hiato entre prática e recomendações. .

OBJETIVOS: evaluar los Programas de Control de Infección Hospitalaria en las instituciones hospitalarias respecto a los indicadores de estructura y proceso. MÉTODO: se trata de un estudio descriptivo, exploratorio y cuantitativo, desarrollado en 2013. La población fue compuesta por 13 Programas de Control de Infección Hospitalaria de servicios de salud de una ciudad brasileña del interior paulista. Fueron utilizados instrumentos de dominio público, disponibles en el Manual de Indicadores de Evaluación de Prácticas de Control de Infección Hospitalaria. RESULTADOS: los indicadores con mayor promedio de conformidad fueron "Evaluación de la Estructura de los Programas de Control de Infección Hospitalaria" (75%) y "Evaluación del Sistema de Vigilancia Epidemiológica de Infección Hospitalaria" (82%) y aquellos con menores promedios "Evaluación de las Directivas Operacionales" (58,97%) y "Evaluación de las Actividades de Control y Prevención de Infección Hospitalaria" (60,29%). CONCLUSIÓN: el uso de indicadores posibilitó identificar que, a pesar del conocimiento producido sobre acciones de prevención y control de infecciones hospitalarias, todavía existe un gran hiato entre la práctica y las recomendaciones. .

Pycnogenol attenuates atherosclerosis by regulating lipid metabolism through the TLR4-NF-kappaB pathway

Atherosclerosis is a leading cause of death worldwide and is characterized by lipid-laden foam cell formation. Recently, pycnogenol (PYC) has drawn much attention because of its prominent effect on cardiovascular disease (CVD). However, its protective effect against atherosclerosis and the underlying mechanism remains undefined. Here PYC treatment reduced areas of plaque and lipid deposition in atherosclerotic mice, concomitant with decreases in total cholesterol and triglyceride levels and increases in HDL cholesterol levels, indicating a potential antiatherosclerotic effect of PYC through the regulation of lipid levels. Additionally, PYC preconditioning markedly decreased foam cell formation and lipid accumulation in lipopolysaccharide (LPS)-stimulated human THP-1 monocytes. A mechanistic analysis indicated that PYC decreased the lipid-related protein expression of adipose differentiation-related protein (ADRP) and adipocyte lipid-binding protein (ALBP/aP2) in a dose-dependent manner. Further analysis confirmed that PYC attenuated LPS-induced lipid droplet formation via ADRP and ALBP expression through the Toll-like receptor 4 (TLR4) and nuclear factor-kappaB (NF-kappaB) pathway, because pretreatment with anti-TLR4 antibody or a specific inhibitor of NF-kappaB (PDTC) strikingly mitigated the LPS-induced increase in ADRP and ALBP. Together, our results provide insight into the ability of PYC to attenuate bacterial infection-triggered pathological processes associated with atherosclerosis. Thus PYC may be a potential lead compound for the future development of antiatherosclerotic CVD therapy.

Effects of supplementation with omega-3 on insulin sensitivity and non-esterified free fatty acid (NEFA) in type 2 diabetic patients / Efeito da suplementação com ômega-3 sobre a sensibilidade à insulina e aos ácidos graxos livres não esterificados (AGNE) em pacientes com diabetes tipo 2

Objective: The aim of this study was to determine the role of omega-3 supplementation on NEFA concentration, insulin sensitivity and resistance, and glucose and lipid metabolism in type 2 diabetic patients. Subjects and methods: Forty-four type 2 diabetic patients were randomly recruited into two groups. Group A received 4 g/day omega-3 soft gels, and group B received a placebo for 10 wks. Blood samples were collected after 12-h fast. Physical activity records, three-day food records, and anthropometric measurements were obtained from all participants at the beginning and end of the study. Results: Omega-3 supplementation caused a significant reduction in NEFA in the intervention group compared with the placebo group (P = 0.009). Additionally, the administration of omega-3 resulted in significantly greater changes (Diff) for the intervention group in various parameters, such as insulin and Quicki indices compared with the placebo group (P < 0.05). Conclusions: Omega-3 fatty acid supplementation in type 2 diabetic patients improved insulin sensitivity, probably due to the decrease in NEFA concentrations. Arq Bras Endocrinol Metab. 2014;58(4):335-40 .

Objetivo: O objetivo deste estudo foi analisar o papel da suplementação com ácidos graxos ômega-3 sobre a concentração de ácidos graxos não esterificados (AGNE), resistência e sensibilidade à insulina e metabolismo de lipídios em pacientes com diabetes melito tipo 2. Sujeitos e métodos: Quarenta e quatro pacientes com diabetes tipo 2 foram recrutados aleatoriamente e alocados em um de dois grupos. O Grupo A recebeu 4 g/dia de ômega-3 na forma de cápsulas gelatinosas e o grupo B recebeu placebo durante 10 semanas. Amostras de sangue foram coletadas após 12 horas de jejum. Registros da atividade física, da dieta de três dias e medidas antropométricas foram obtidos de todos os participantes no início e no final do estudo. Resultados: A suplementação com ômega-3 causou uma redução significativa na AGNE em comparação com grupo placebo (P = 0,008). Além disso, a administração de ômega-3 resultou em alterações significativamente maiores (Dif) em vários parâmetros, tais como a insulina, HOMA-IR e QUICKI, comparando com placebo (P < 0,05). Conclusões: A suplementação com ácidos graxos ômega-3 em pacientes diabéticos tipo 2 melhorou a sensibilidade à insulina, provavelmente devido à diminuição da concentração de AGNE. Arq Bras Endocrinol Metab. 2014;58(4):335-40 .

The impact of pegylated interferon and ribavirin combination treatment on lipid metabolism and insulin resistance in chronic hepatitis C patients

BACKGROUND/AIMS: Lipid profile and insulin resistance (IR) are associated with hepatitis C virus (HCV) and may predict the chronic hepatitis C (CHC) treatment response. The aim of this study was to determine the association between CHC treatment response and lipid profile and IR change during treatment. METHODS: In total, 203 CHC patients were reviewed retrospectively between January 2005 and December 2011 at Soon Chun Hyang University Hospital. The lipid profile, homeostasis model for assessment (HOMA) of IR (HOMA-IR), and HOMA of beta cells (HOMA-beta) were evaluated before interferon plus ribavirin therapy (BTx), at the end of treatment (DTx), and 24 weeks after the end of treatment (ATx). RESULTS: A sustained virologic response (SVR) was achieved by 81% of all patients (49/60), 60% (n=36) of whom possessed genotype 1, with the remainder being non-genotype-1 (40%, n=24). Apart from age, which was significantly higher in the non-SVR group (SVR, 48.0+/-11.2 years, mean+/-SD; non-SVR, 56.6+/-9.9 years; P2.5), HOMA-IR was significantly changed at DTx in the SVR group. CONCLUSIONS: LDL-C appears to be associated with HCV treatment in SVR patients. Furthermore, eradication of HCV may improve whole-body IR and insulin hypersecretion, as well as high baseline insulin resistance (HOMA-IR >2.5).

Efecto de la hidroxicloroquina sobre la sensibilidad a la insulina y el perfil de lípidos en pacientes con artritis reumatoide / Effects of hydroxychloroquine on insulin sensitivity and lipid profile in patients with rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is associated with a decrease in insulin sensitivity (IS), which has been identified as an independent risk factor for the development of early atherosclerosis. Hydroxychloroquine (HCQ) may have beneficial effects on glucose homeostasis and lipid profile. Aim: To assess the effect of HCQ on IS and lipid profile in patients with RA. Material and Methods: An open clinical trial was performed in 15 patients aged between 35 and 56 years. During three months, patients received 400 mg/day of HCQ orally. Before and after the pharmacological intervention, demographic and anthropometric variables, serum glucose, total cholesterol (TC), triglycerides (TG), HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, insulin and uric acid were measured. IS was estimated as the rate of glucose clearance per minute obtained with the insulin tolerance test (KITT). Results: Baseline and final KITT values were 4.3 ± 1.2 and 4.80 ± 1.1%/min, respectively (p = 0.03). Significant reductions in serum TC (p = 0.04) and TG (p = 0.01) were also observed. No other significant differences were observed. Conclusions: Oral administration of 400 mg/day of HCQ during three months in RA patients is associated with an improvement in IS, TC and TG.

Lipid profile of HIV-infected patients in relation to antiretroviral therapy: a review / Perfil lipídico de pacientes infectados pelo HIV em relação à terapia antirretroviral: uma revisão

This study reviewed the lipid profile of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in relation to use of antiretroviral therapy (ART), and its different classes of drugs. A total of 190 articles published in peer-reviewed journals were retrieved from PubMed and LILACS databases; 88 of them met the selection criteria and were included in the review. Patients with HIV/AIDS without ART presented an increase of triglycerides and decreases of total cholesterol, low density lipoprotein (LDL-c), and high density lipoprotein (HDL-c) levels. Distinct ART regimens appear to promote different alterations in lipid metabolism. Protease inhibitors, particularly indinavir and lopinavir, were commonly associated with hypercholesterolemia, high LDL-c, low HDL-c, and hypertriglyceridemia. The protease inhibitor atazanavir is apparently associated with a more advantageous lipid profile. Some nucleoside reverse-transcriptase inhibitors (didanosine, stavudine, and zidovudine) induced lipoatrophy and hypertriglyceridemia, whereas abacavir increased the risk of cardiovascular diseases even in the absence of apparent lipid disorders, and tenofovir resulted in lower levels of cholesterol and triglycerides. Although non-nucleoside reverse-transcriptase inhibitors predisposed to hypertriglyceridemia and hypercholesterolemia, nevirapine was particularly associated with high HDL-c levels, a protective factor against cardiovascular diseases. Therefore, the infection itself, different classes of drugs, and some drugs from the same class of ART appear to exert distinct alterations in lipid metabolism.

Este estudo faz uma revisão sobre o perfil lipídico de pacientes com vírus da imunodeficiência humana/síndrome da imunodeficiência adquirida (HIV/AIDS) em relação ao uso da terapia antirretroviral (TARV), e suas diferentes classes de fármacos. Um total de 190 artigos publicados em revistas indexadas foram selecionados das bases de dados PubMed e LILACS; 88 deles preencheram os critérios de seleção e foram incluídos nesta revisão. Pacientes com HIV/AIDS sem uso de TARV apresentaram aumento de triglicérides e diminuição dos níveis de colesterol total, lipoproteína de baixa densidade (LDL-c) e lipoproteína de alta densidade (HDL-c). Distintos regimes de TARV promoveram diferentes alterações no metabolismo lipídico. Inibidores de protease, particularmente indinavir e lopinavir, foram comumente associados com hipercolesterolemia, aumento de LDL-c, diminuição de HDL-c e hipertrigliceridemia. O inibidor de protease atazanavir aparentemente está associado a menores alterações do perfil lipídico. Alguns inibidores da transcripitase reversa análogos de nucleosídeos (didanosina, estavudina e zidovudina), induziram lipoatrofia e hipertrigliceridemia, enquanto o abacavir aumentou o risco cardiovascular mesmo na ausência de aparentes distúrbios lipídicos, e o tenofovir resultou em menores níveis de colesterol e triglicérides. Embora os inibidores da transcriptase reversa não análogos de nucleosídeos possam predispor a hipertrigliceridemia e hipercolesterolemia, a nevirapina, particularmente, foi associada a maiores níveis de HDL-c, um fator de proteção contra doenças cardiovasculares. Portanto, a própria infecção, diferentes classes de fármacos e alguns fármacos da mesma classe de TARV podem exercer distintas alterações no metabolismo lipídico.

Effect and the probable mechanisms of silibinin in regulating insulin resistance in the liver of rats with non-alcoholic fatty liver

Our previous study has shown that reduced insulin resistance (IR) was one of the possible mechanisms for the therapeutic effect of silibinin on non-alcoholic fatty liver disease (NAFLD) in rats. In the present study, we investigated the pathways of silibinin in regulating hepatic glucose production and IR amelioration. Forty-five 4- to 6-week-old male Sprague Dawley rats were divided into a control group, an HFD group (high-fat diet for 6 weeks) and an HFD + silibinin group (high-fat diet + 0.5 mg kg-1·day-1 silibinin, starting at the beginning of the protocol). Both subcutaneous and visceral fat was measured. Homeostasis model assessment-IR index (HOMA-IR), intraperitoneal glucose tolerance test and insulin tolerance test (ITT) were performed. The expression of adipose triglyceride lipase (ATGL) and of genes associated with hepatic gluconeogenesis was evaluated. Silibinin intervention significantly protected liver function, down-regulated serum fat, and improved IR, as shown by decreased HOMA-IR and increased ITT slope. Silibinin markedly prevented visceral obesity by reducing visceral fat, enhanced lipolysis by up-regulating ATGL expression and inhibited gluconeogenesis by down-regulating associated genes such as Forkhead box O1, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Silibinin was effective in ameliorating IR in NAFLD rats. Reduction of visceral obesity, enhancement of lipolysis and inhibition of gluconeogenesis might be the underlying mechanisms.

Efeitos da atorvastatina e do polimorfismo T-786C do gene eNOS sobre parâmetros do metabolismo lipídico plasmático / Effects of atorvastatin and T-786C polymorphism of eNOS gene on plasma metabolic lipid parameters

FUNDAMENTO: A atividade do óxido nítrico sintase endotelial (eNOS) pode ser modulada pelo colesterol da lipoproteína de alta densidade (HDL-C), estatinas ou polimorfismos, como o T-786C de eNOS. OBJETIVO: Este estudo teve como objetivo avaliar se o polimorfismo T-786C está associado a alterações nos efeitos da atorvastatina no perfil lipídico, nas concentrações de metabólitos de óxido nítrico (NO) e da proteína C reativa de alta sensibilidade (PCR-as). MÉTODOS: Trinta voluntários do sexo masculino, assintomáticos, com idade entre 18-56 anos foram genotipados e classificados de acordo com a ausência (TT, n = 15) ou presença (CC, n = 15) do polimorfismo. Eles foram selecionados aleatoriamente para a utilização de placebo e atorvastatina (10 mg/dia por 14 dias). Após cada tratamento foram medidos lípides, lipoproteínas, frações HDL2 e HDL3, atividade da proteína de transferência de colesteril éster (CETP), metabólitos de NO e PCR-as. RESULTADOS: As comparações entre genótipos após a administração de placebo mostraram aumento da atividade da CETP polimorfismo-dependente (TT, 12 ± 7; CC, 22 ± 12, p < 0,05). As análises da interação entre os tratamentos indicaram que a atorvastatina tem efeito sobre colesterol, LDL, nitrito e razões lípides/proteínas (HDL2 e HDL3) (p < 0,001) em ambos os genótipos. É interessante notar as interações genótipo/droga sobre a CETP (p < 0,07) e a lipoproteína (a) [Lp(a)] (p < 0,056), levando a uma diminuição limítrofe da CETP, embora sem afetar a Lp(a). A PRC-as não mostrou alterações. CONCLUSÃO: Os resultados sugerem que o tratamento com estatinas pode ser relevante para a prevenção primária da aterosclerose em pacientes com o polimorfismo T-786C do eNOS, considerando os efeitos no metabolismo lipídico.

BACKGROUND: Endothelial nitric oxide synthase (eNOS) activity may be modulated by high-density lipoprotein cholesterol (HDL-C), statins or polymorphisms, such as the T-786C of eNOS. OBJECTIVE: This study aimed at evaluating if the T-786C polymorphism is associated with changes of atorvastatin effects on the lipid profile, on the concentrations of metabolites of nitric oxide (NO) and of high sensitivity C-reactive protein (hsCRP). METHODS: Thirty male volunteers, asymptomatic, aged between 18 and 56 years were genotyped and classified according to absence (TT, n = 15) or presence (CC, n = 15) of the polymorphism. They were randomly selected for the use of placebo or atorvastatin (10 mg/day/14 days). After each treatment lipids, lipoproteins, HDL2 and HDL3 composition, cholesteryl ester transfer protein (CETP) activity, metabolites of NO and hsCRP were evaluated. RESULTS: The comparisons between genotypes after placebo showed an increase in CETP activity in a polymorphism-dependent way (TT, 12±7; CC, 22±12; p < 0.05). The interaction analyses between treatments indicated that atorvastatin has an effect on cholesterol, LDL, nitrite and lipid-protein ratios (HDL2 and HDL3) (p < 0.001) in both genotypes. Interestingly, we observed genotype/drug interactions on CETP (p < 0.07) and lipoprotein (a) (Lp(a)) (p < 0.056), leading to a borderline decrease in CETP, but with no effect on Lp(a). HsCRP showed no alteration. CONCLUSION: These results suggest that statin treatment may be relevant for primary prevention of atherosclerosis in patients with the T-786C polymorphism of eNOS, considering the effects on lipid metabolism.

Effect of the combination of metformin and fenofibrate on glucose homeostasis in diabetic Goto-Kakizaki rats

Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-alpha-dependent manner. We investigated whether a PPARalpha agonist, fenofibrate, exhibits an additive or synergistic effect on glucose metabolism, independent of its lipid-lowering effect, when added to metformin. Non-obese diabetic Goto-Kakizaki (GK) rats were divided into four groups and treated for 28 days with metformin, fenofibrate, metformin plus fenofibrate or vehicle. The random blood glucose levels, body weights, food intake and serum lipid profiles were not significantly different among the groups. After 4 weeks, metformin, but not fenofibrate, markedly reduced the blood glucose levels during oral glucose tolerance tests, and this effect was attenuated by adding fenofibrate. Metformin increased the expression of the GLP-1 receptor in pancreatic islets, whereas fenofibrate did not. During the intraperitoneal glucose tolerance tests with the injection of a GLP-1 analog, metformin and/or fenofibrate did not alter the insulin secretory responses. In conclusion, fenofibrate did not confer any beneficial effect on glucose homeostasis but reduced metformin's glucose-lowering activity in GK rats, thus discouraging the addition of fenofibrate to metformin to improve glycemic control.

Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes

This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve beta-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients.

Exendin-4 improves resistance to Listeria monocytogenes infection in diabetic db/db mice

The incidence of diabetes mellitus is increasing among companion animals. This disease has similar characteristics in both humans and animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In the present study, homozygous diabetic (db/db) mice were infected with Listeria (L.) monocytogenes and then treated with the anti-diabetic drug exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b+ macrophage populations with higher lipid content and lower phagocytic activity were observed. Exendin-4 lowered high lipid levels and enhanced phagocytosis in macrophages from db/db mice infected with L. monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved ex vivo bacteria clearance by macrophages in the animals. Liver histology examined during L. monocytogenes infection indicated that abscess formation was much milder in exendin-4-treated db/db mice than in the control animals. Moreover, mechanistic studies demonstrated that expression of ATP binding cassette transporter 1, a sterol transporter, was higher in macrophages isolated from the exendin-4-treated db/db mice. Overall, our results suggest that exendin-4 decreases the risk of infection in diabetic animals by modifying the interaction between intracellular lipids and phagocytic macrophages.