High Prevalence of Familial Hypercholesterolemia Due to the Founder Effect of the LDLR c.2271del Variant in Communities of Oaxaca, Mexico.

INTRODUCTION: In Mexico, familial hypercholesterolemia (FH) is underdiagnosed, but population screening in small communities where at least one homozygous patient has already been detected results in a useful and inexpensive approach to reduce this problem. Considering that we previously reported nine homozygous cases from the state of Oaxaca, we decided to perform a population screening to identify patients with FH and to describe both their biochemical and genetic characteristics. METHODS: LDL cholesterol (LDLc) was quantified in 2,093 individuals from 11 communities in Oaxaca; either adults with LDLc levels ≥170 mg/dL or children with LDLc ≥130 mg/dL were classified as suggestive of FH and therefore included in the genetic study. LDLR and APOB (547bp fragment of exon 26) genes were screened by sequencing and MLPA analysis. RESULTS: Two hundred and five individuals had suggestive FH, with a mean LDLc of 223 ± 54 mg/dL (range: 131-383 mg/dL). Two pathogenic variants in the LDLR gene were detected in 149 individuals: c.-139_-130del (n = 1) and c.2271del (n = 148). All patients had a heterozygous genotype. With the cascade screening of their relatives (n = 177), 15 heterozygous individuals for the c.2271del variant were identified, presenting a mean LDLc of 133 ± 35 mg/dL (range: 60-168 mg/dL). CONCLUSIONS: The FH frequency in this study was 7.8% (164/2093), the highest reported worldwide. A founder effect combined with inbreeding could be responsible for the high percentage of patients with the LDLR c.2271del variant (99.4%), which allowed us to detect both significant biochemical heterogeneity and incomplete penetrance; hence, we assumed the presence of phenotype-modifying variants.

Olive oil increases the LIPC expression when associated with an Eastern pattern diet: An experimental study with Wistar rats.

Some nutrigenomic effects of extra virgin olive oil (EVOO) are described in the literature; however, it is unknown whether its interaction with lipid-related genes is independent of the combined diet. In this sense, our objective was to investigate whether EVOO consumption associated with Western or Eastern human-based chow modulates the expression of APOE, APOB, and LIPC genes in rats. In view of this, the hypothesis is that the consumption of olive oil may not have the same nutrigenomic effects, depending on the diet consumed. For this study, 56 female rats were randomly divided into four groups: Western diet with EVOO (WS), Western-diet control (WC), Eastern-diet with EVOO (ES), and Eastern-diet control (EC). After 15 weeks, the animals were anesthetized with an intraperitoneal injection of chloral hydrate 15% (1.5 mL/kg) and euthanized by guillotining, and adipose tissue, liver, and blood were extracted. Triglycerides, cholesterol, and glucose levels were obtained following standard protocols, and relative gene expressions were calculated using the ΔΔCt method after quantitative PCR. The EVOO consumption was associated with LIPC gene expression increase in the liver only in animals fed the Eastern diet, compared to EC and WS animals. The EVOO consumption, combined with the Eastern diet, was associated with decreased triglyceride levels compared to WC. Although final weight and weight gain were similar between groups, WS animals had lower daily energy consumption. Conclusion: Given these results, the authors suggested that the EVOO nutrigenomic effects were restricted to an Eastern human-based diet.

Lean adolescents with insulin resistance display higher angiopoietin like protein 3, ApoC-III and chylomicron remnant dyslipidemia.

BACKGROUND: Triglyceride-rich lipoproteins (TRL: chylomicrons and VLDL) are a key component of diabetes dyslipoproteinemia and cardiovascular risk. We have shown that it is already prevalent in obese adolescents in association with lipoprotein lipase (LPL) dysregulation. Insulin resistance (IR) suffices to produce TRL dyslipoproteinemia and LPL dysfunction even in the absence of obesity. METHODS: This cross-sectional study included euglycemic adolescents between 15 and 19 y, classified in 4 groups according to BMI, HOMA-IR and fasting lipid as: metabolically healthy lean (MHL, n = 30), metabolically unhealthy lean (MUL, n = 25), metabolically healthy obese (MHO, = 30), and metabolically unhealthy obese (MUO, n = 42). RESULTS: As compared to MHL, MUL participants showed 73% higher concentrations of ApoB-48; 84% of ApoC-III; 24% ANGPTL-3; 200% of TG; 218% of VLDL-C and 238% of TG/HDL-C c, No changes were found in LPL mass. Interestingly, the differences in these parameters between MUL and MHO were not significant. CONCLUSION: Euglycemic lean adolescents with IR display TRL dyslipoproteinemia with increased inhibition of LPL as highlighted by higher concentrations of ANGPTL-3, ApoC-III and fasting chylomicron remnants (ApoB-48).

Common Bean Baked Snack Consumption Reduces Apolipoprotein B-100 Levels: A Randomized Crossover Trial.

Snack alternatives based on common beans (Phaseolus vulgaris L.) have been developed to promote pulse consumption. The purpose of this study was to evaluate the chemical composition, sensory acceptance and the effect of common bean baked snack (CBBS) consumption on blood lipid levels in participants with overweight and altered blood lipid levels. A sensory evaluation by 80 untrained judges was carried out using a hedonic scale. A randomized crossover 2 × 2 trial was performed, where 20 participants with overweight and one blood lipid alteration consumed 32 g of CBBS or did not consume it (control) for four weeks. Blood samples were taken to quantify the triglycerides, total cholesterol, LDL-c, HDL-c, ApoB-100, glucose and insulin. Furthermore, anthropometric, dietary and physical activity parameters were recorded. The overall acceptance of CBBS was similar compared to popcorn (p > 0.05). The consumption of CBBS reduced the apolipoprotein B-100 levels (p = 0.008). This reduction could be associated with the additional dietary fiber consumption during the CBBS period (p = 0.04). Although it did not improve any other blood lipid or glucose parameters (p > 0.05), it did not affect them either, which means that the CBBS could be consumed without compromising cardiovascular health.

Prognostic value of apolipoproteins in COVID-19 patients: A systematic review and meta-analysis.

INTRODUCTION: Apolipoproteins are predictive biomarkers for cardiovascular, neoplasms and cerebrovascular diseases and are postulated as prognostic biomarkers in infectious diseases, as COVID-19. Thus, we assessed the prognosis value of apolipoproteins for COVID-19 severity and mortality. METHODS: We conducted a systematic review and meta-analysis using observational studies that reported the association between apolipoproteins and severity or mortality in COVID-19 patients. Newcastle-Ottawa was used for the quality assessment of included studies. Effects measurements were shown as odds ratios (ORs) with 95% confidence intervals (CIs), and Egger-test was developed for assessing the risk of bias publication. RESULTS: We analyzed 12 cohort studies (n = 3580). Patients with low ApoliproteinA1 (ApoA1) (OR 0.35; 95%CI 0.24 to 0.49; P < 0.001) and ApoliproteinB (ApoB) (OR = 0.78; 95%CI 0.69 to 0.87; P < 0.001) values had a higher risk of developing severe disease. ApoB/ApoA1 ratio showed no statistically significant association with higher odds of severity. Low ApoA1 levels were associated with higher odds of all-cause mortality (OR = 0.34; 95%CI 0.20 to 0.57; P < 0.001). ApoB values showed no statistically significant association with a high risk of all-cause mortality. CONCLUSION: We suggest that adequate levels of ApoA1 and ApoB can be a protective factor for severity in COVID-19, and ApoB/ApoA1 ratio did not show predictive utility for severity.

Small interfering RNA for cancer treatment: overcoming hurdles in delivery.

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.

Fatty acid nitration in human low-density lipoprotein.

Lipid nitration occurs during physiological and pathophysiological conditions, generating a variety of biomolecules capable to modulate inflammatory cell responses. Low-density lipoprotein (LDL) oxidation has been extensively related to atherosclerotic lesion development while oxidative modifications confer the particle pro-atherogenic features. Herein, we reviewed the oxidation versus nitration of human LDL protein and lipid fractions. We propose that unsaturated fatty acids present in LDL can be nitrated under mild nitration conditions, suggesting an anti-atherogenic role for LDL carrying nitro-fatty acids (NFA).

Hypercholesterolemia Due to Lipoprotein X: Case Report and Thematic Review.

The liver is a key organ in lipid and lipoprotein metabolism, hence hepatic diseases often manifest as lipid disturbances. Cholestatic liver diseases are frequently associated with an important increase in total cholesterol at the expense of lipoprotein X (LpX), an abnormal lipoprotein isolated and characterized in the 1960s to 1970s in patients with obstructive jaundice. Lipoprotein X is rich in phospholipids, albumin, and free cholesterol, has a density similar to low-density lipoprotein (LDL), and a size similar to very low-density lipoprotein (VLDL), which has hampered its detection through routine laboratory tests. Unlike LDL, LpX has no apoB-100, so it is not removed from circulation via the LDL receptor, and it is not clear whether or not it can be atherogenic. Although LpX was initially described in patients with cholestasis, it has also been found in patients with genetic deficiency of lecithin-cholesterol acyltransferase (LCAT), in patients who receive lipid-rich parenteral nutrition and most recently in patients with graft versus host disease of the liver. In the presence of LpX, plasma total cholesterol can rise up to 1000 mg/dL, which may lead to the development of skin xanthomas and hyperviscosity syndrome. Treatment of LpX-dependent hypercholesterolemia with conventional hypolipidemic drugs is frequently ineffective, and definitive treatment relies on correction of the underlying cause of cholestasis. Here, we present the case of a patient with LpX-dependent hypercholesterolemia in the context of primary biliary cholangitis.

Phenotypic severity in a family with MEND syndrome is directly associated with the accumulation of potentially functional variants of cholesterol homeostasis genes.

BACKGROUND: Male EBP disorder with neurologic defects (MEND) syndrome is an X-linked disease caused by hypomorphic mutations in the EBP (emopamil-binding protein) gene. Modifier genes may explain the clinical variability among individuals who share a primary mutation. METHODS: We studied four males (Patient 1 to Patient 4) exhibiting a descending degree of phenotypic severity from a family with MEND syndrome. To identify candidate modifier genes that explain the phenotypic variability, variants of homeostasis cholesterol genes identified by whole-exome sequencing (WES) were ranked according to the predicted magnitude of their effect through an in-house scoring system. RESULTS: Twenty-seven from 105 missense variants found in 45 genes of the four exomes were considered significant (-5 to -9 scores). We found a direct genotype-phenotype association based on the differential accumulation of potentially functional gene variants among males. Patient 1 exhibited 17 variants, both Patients 2 and 3 exhibited nine variants, and Patient 4 exhibited only five variants. CONCLUSION: We conclude that APOA5 (rs3135506), ABCA1 (rs9282541), and APOB (rs679899 and rs12714225) are the most relevant candidate modifier genes in this family. Relative accumulation of the deficiencies associated with variants of these genes along with other lesser deficiencies in other genes appears to explain the variable expressivity in MEND syndrome.

Ultrassequenciamento exômico dos principais genes relacionados com a hipercolesterolemia familial / Ultrasequensing exomic of the main genes related to familial hypercholesterolemia

A frequência de Hipercolesterolemia Familial (HF) ainda é desconhecida no Brasil, principalmente pela ausência de estudos com caracterização genotípica associada à fenotípica. Os dados epidemiológicos existentes se baseiam apenas no fenótipos e carecem do diagnóstico molecular confirmatório. O objetivo do presente estudo foi identificar as principais causas genéticas da HF em pacientes diagnosticados fenotipicamente através de um painel exômico com 61 genes a fim de contribuir para um sistema de confirmação do diagnostico molecular em uma amostra da população brasileira. Para isso foram incluídos 141 pacientes, não aparentados, portadores de HF atendidos pelo setor de dislipidemias do Instituto Dante Pazzanese de Cardiologia, Laboratório de Analises Clinicas da Faculdade de Ciências Farmacêuticas da Universidade Federal do Rio Grande do Norte e do Programa Hipercol Brasil do Instituto do Coração. As amostras de sangue periférico foram obtidas para determinações fenotípicas laboratoriais e extração de DNA genômico. A biblioteca de DNA foi construída utilizando o kit Nextera® Rapid Capture Enrichment Custom enriquecendo os éxons de 61 genes que direta ou indiretamente estão relacionados com metabolismo do colesterol. O ultrassequenciamento foi realizado utilizando kit MiSeq Reagent (300 a 500 ciclos) na plataforma MiSeq (Illumina). Os resultados de sequenciamento foram inicialmente alinhados a uma sequência referência e analisados para eliminação de falsos positivos, segundo os parâmetros de qualidade, tais como: cobertura mínima de 30x, frequência do alelo alterado maior que 20% e diferença da distribuição das leituras entre as sequências nucleotídicas menor que 15%. Foram identificadas 472 diferentes variantes em 56 dos genes presentes no painel, sendo 45 consideradas como não descritas. Nos genes APOA1, APOA2, LIPC, RBP4 e TIMP1 não foram observadas variantes dentro dos critérios estabelecidos. Das variantes observadas 25 identificadas em 30 (21,2%) pacientes já tinha sido publicadas em relação à HF nos três principais genes (LDLR, APOB e PCSK9), confirmando o diagnóstico. Foi caracterizado genotipicamente outras dislipidemias primárias em 7 pacientes, sem diagnóstico molecular de HF, através de variantes identificadas no ultrassequenciamento em outros genes. Dos 104 pacientes que não possuíam nenhuma variante já previamente caracterizada, 69 possuíam variantes relacionados com o metabolismo do colesterol. As variantes sem patogenicidade conhecida foram avaliadas através de ferramentas de predição in silico e 22 delas possuíam características sugestivas de patogenicidade em pelo menos 4 das ferramentas utilizadas, duas delas também mostraram alterar a estrutura da proteína segundo análises de docking molecular. Foram identificadas também 223 variantes em região não transcritas (UTR). Quando realizada as análises estatística de todas as variantes identificadas, observamos associação de 13 variantes com concentrações mais elevadas de colesterol da LDL, 5 com concentrações mais elevadas de apolipoproteina B-100, 5 com concentrações mais elevadas de colesterol total, 6 com presença de arco córneo, 2 com manifestação de xantelasmas, 2 com ausência de xantomas e 3 com a presença de doença arterial coronariana. Dessas 6 variantes já haviam sido previamente descritas com HF ou algum outro fenótipo associado e 2 não tinham citação na literatura pesquisada, mas possuíam característica patogênica para a proteína segundo as ferramentas de predição in silico. Este estudo permitiu a identificação das causas genéticas da HF em pacientes brasileiros diagnosticados fenotipicamente, mostrando que a técnica escolhida permitiu caracterizar 21,2% dos pacientes. Além disso, foi possível identificar outras dislipidemias primárias e caracterizar algumas variantes que, apesar de necessitarem serem validadas, indicam uma possível associação com a HF, aumentando o esclarecimento do fenótipo com o genótipo para 74,5%. Este estudo também possibilitou a identificação de novas variantes que devem ser avaliadas para confirmar associação com a doença e utilizar para o diagnóstico propondo um novo painel poligênico

The frequency of Familial Hypercholesterolemia (FH) is still unknown in Brazil, mainly due to the absence of studies with genotypic characterization associated with phenotype. Existing epidemiological data are based only on the phenotypes and lack the confirmatory molecular diagnosis. The aim of the present study was to identify main genetic causes of FH in patients diagnosed phenotypically through an exomic panel with 61 genes in order to contribute to a system of confirmation molecular diagnosis in a sample of the Brazilian population. To this end, 141 non-related patients with FH treated by the dyslipidemia sector of the Institute Dante Pazzanese of Cardiology, Clinical Analysis Laboratory of the Faculty of Pharmaceutical Sciences of the University Federal of Rio Grande do Norte and the Hipercol Brazil Program of the Heart Institute. Peripheral blood samples were obtained for laboratory phenotypic determinations and extraction of genomic DNA. The DNA library was constructed using the Nextera® Rapid Capture Enrichment Custom kit, enriching with éxons of 61 genes that are directly or indirectly related to cholesterol metabolism. Ultrasequencing was performed using MiSeq Reagent kit (300 to 500 cycles) on the MiSeq platform (Illumina). The sequencing results were initially aligned to a reference sequence and analyzed for false positive elimination according to quality parameters such as: minimum coverage of 30x, altered allele frequency greater than 20%, and difference in the distribution of reads between sequences nucleotides less than 15%. 472 different variants were identified in 56 of the genes present in the panel, of which 45 were considered not described. In the APOA1, APOA2, LIPC, RBP4 and TIMP1 genes no variants were observed within the established criteria. In 25 of the variants observed presents in 30 (21.2%) patients had already been published in relation to FH in the three main genes (LDLR, APOB and PCSK9), confirming the diagnosis. Other primary dyslipidemias were caracterized genotypically in 7 patients, without molecular diagnosis of HF, through variants identified in ultrasequencing in other genes. Of the 104 patients who did not have any previously characterized variant, 69 had variants related to cholesterol metabolism. The variants without known pathogenicity were evaluated using in silico prediction tools and 22 of them had characteristics suggestive of pathogenicity at least 4 of the tools used, two of them also showed to alter the structure of the protein according to molecular docking analyzes. Were also identified 223 non-transcribed region (UTR) variants. Statistical analysis of all the variants identified showed association of 13 variants with higher concentrations of LDL cholesterol, 5 with higher concentrations of apolipoprotein B-100, 5 with higher concentrations of total cholesterol, 6 with presence of an arc corneal, 2 with manifestation of xanthelasms, 2 with absence of xanthomas and 3 with the presence of coronary artery disease. Of these 6 variants had previously been described with HF or some other associated phenotype and 2 had no citation in the researched literature, but had a pathogenic characteristic for the protein according to in silico prediction tools. This study allowed the identification of the genetic causes of FH in Brazilian patients diagnosed phenotypically, showing that the technique chosen allowed to characterize 21.2% of the patients. In addition, it was possible to identify other primary dyslipidemias and to characterize some variants that, although they need to be validated, indicate a possible association with HF, increasing the clarification of the phenotype with the genotype to 74.5%. This study also allowed the identification of new variants that should be evaluated to confirm association with the disease and to use for the diagnosis proposing a new polygenic panel

Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol and early cardiovascular disease. As cardiovascular disease is a leading cause of mortality in Argentina, early identification of patients with FH is of great public health importance. OBJECTIVE: The aim of our study was to identify families with FH and to approximate to the characterization of the genetic spectrum mutations of FH in Argentina. METHODS: Thirty-three not related index cases were selected with clinical diagnosis of FH. Genetic analysis was performed by sequencing, multiplex ligation-dependent probe amplification, and bioinformatics tools. RESULTS: Twenty genetic variants were identified among 24 cases (73%), 95% on the low-density lipoprotein receptor gene. The only variant on APOB was the R3527Q. Four were novel variants: c.-135C>A, c.170A>C p.(Asp57Ala), c.684G>C p.(Glu228Asp), and c.1895A>T p.(Asn632Ile); the bioinformatics' analysis revealed clear destabilizing effects for 2 of them. The exon 14 presented the highest number of variants (32%). Four variants were observed in more than 1 case and the c.2043C>A p.(Cys681*) was carried by 18% of index cases. Two true homozygotes, 3 compound heterozygotes, and 1 double heterozygote were identified. CONCLUSION: This study characterizes for the first time in Argentina genetic variants associated with FH and suggest that the allelic heterogeneity of the FH in the country could have 1 relative common low-density lipoprotein receptor mutation. This knowledge is important for the genotype-phenotype correlation and for optimizing both cholesterol-lowering therapies and mutational analysis protocols. In addition, these data contribute to the understanding of the molecular basis of FH in Argentina.

Complejos inmunes IgM-ApoB100 modificadas / Immune complexes IgM-modified ApoB100 / Complexos Imunes IgM-ApoB100 modificadas

La aterosclerosis es la patología vascular de mayor prevalencia, lo cual motiva numerosas investigaciones sobre su fisiopatogenia. Las lipoproteínas pueden ser modificadas por mecanismos de oxidación y acetilación entre otros, a nivel de sus componentes lipídicos como proteicos, tornándose aterogénicas. Las Apolipoproteínas B100 modificadas (ApoB100m), desempeñan un rol activo en el desarrollo de las lesiones ateroscleróticas conjuntamente con otros factores de riesgo. Éstas tienen la capacidad de producir respuesta inmune llevando a la producción de anticuerpos y la subsecuente formación de complejos inmunes. La importancia de los anticuerpos contra las ApoB100m en la aterogénesis todavía no está clara, existiendo datos contradictorios respecto a si su rol es protectivo o aterogénico. Se establecieron dos objetivos: Determinar los niveles de complejos inmunes circulantes IgM-ApoB100m por enzimoinmunoanálisis, en sujetos normales (sin riesgo aterogénico) y pacientes con alto riesgo y establecer su correlación con los factores de riesgo aterogénico ya establecidos, mediante un estudio observacional transversal. Se obtuvieron valores medios más elevados de IgM-ApoB100m en el grupo de sujetos normales. Los complejos inmunes IgM-ApoB100m correlacionan negativamente con los factores de riesgo aterogénicos clásicos (sexo masculino, avanzada edad, dislipemia, LDL-C aumentado y HDL-C disminuido).

Atherosclerosis is the most prevalent vascular disease, which motivates extensive research on its pathogenesis. Lipoproteins can be modified by acetylation and oxidation mechanisms, at the level of lipid components as protein, becoming atherogenic. Modified Apolipoprotein B100 (ApoB100m), play an active role in the development of atherosclerotic lesions in conjunction with other risk factors. These have the ability to produce immune response leading to antibody production and subsequent formation of immune complexes. The importance of antibodies against ApoB100m in atherogenesis is still unclear since, contradictory data exist on whether their role is protective or atherogenic. Two objectives were established: to determine the levels of circulating immune complexes IgM-ApoB100m by enzyme immunoassay, in normal subjects (without atherogenic risk) and high-risk patients and to establish its correlation with atherogenic risk factors established by a cross-sectional study. Higher mean values of IgM-ApoB100m were obtained in the group of normal subjects. Immune complexes IgM-ApoB100 negatively correlated with classic atherogenic risk factors (male, older, dyslipidemia, increased LDL-C and decreased HDL-C).

A aterosclerose é a doença vascular mais prevalente, o que motiva numerosas pesquisas sobre sua patogênese. As lipoproteínas podem ser modificadas por meio de mecanismos de oxidação e de acetilação entre outros, em nível de seus componentes lipídicos como proteicos, tornando-se aterogênicas. As apolipoproteínas B100 modificadas (ApoB100m), desempenham um papel ativo no desenvolvimento de lesões ateroscleróticas em conjunto com outros fatores de risco. Elas têm a capacidade de produzir resposta imune que conduz à produção de anticorpos e subsequente formação de complexos imunes. A importância de anticorpos contra a ApoB100m na aterogênese ainda não é clara, existindo dados contraditórios sobre se seu papel é de proteção ou aterogênico. Foram estabelecidos dois objetivos. Determinar os níveis de complexos imunes circulantes IgM-ApoB100m por enzimoimunoanálise em indivíduos normais (sem risco aterogênico) e pacientes de alto risco e, estabelecer sua correlação com os fatores de risco aterogênico já estabelecidos por um estudo Observacional Transversal. Foram obtidos valores médios mais elevados de IgM-ApoB100m no grupo de indivíduos normais. Os complexos imunes IgM-ApoB100 correlacionam negativamente com os fatores de risco aterogênicos clássicos (sexo masculino, idosos, dislipidemia, LDL-C aumentado e HDL-C diminuído).

Correlation Analysis of Relative Expression of Apob, Adfp and Fatp1 with Lipid Metabolism in Daweishan Mini Chickens

Quantitative RT-PCR was applied to measure the relative expression levels of the adipose differentiation-related protein (ADFP) gene, fatty acid transport protein 1 (FATP1) gene and apolipoprotein B (ApoB) gene in subcutaneous fat, abdominal fat, liver and muscle at five growth stages (28, 49, 70, 91 and 112 d) to determine the effect of the expression ofthese genes on fat deposition in Daweishan Mini chickens.The relative expression of ADFP gene mRNA in the abdominal fat andthe liver was significantly different between 49 d and 70 d (p 0.05). The relative ApoB gene expression on 91d was higher in the liver, followed by muscles,subcutaneous fat, and abdominal fat, and was significantly higher in the liver than in the other three tissues. FATP1 gene expression in the liver presented a significant positive correlation with subcutaneous fat thickness (p 0.05). The results of this study suggest that the three genes may control the fat development in Daweishan Mini chicken

Correlation Analysis of Relative Expression of Apob, Adfp and Fatp1 with Lipid Metabolism in Daweishan Mini Chickens

Quantitative RT-PCR was applied to measure the relative expression levels of the adipose differentiation-related protein (ADFP) gene, fatty acid transport protein 1 (FATP1) gene and apolipoprotein B (ApoB) gene in subcutaneous fat, abdominal fat, liver and muscle at five growth stages (28, 49, 70, 91 and 112 d) to determine the effect of the expression ofthese genes on fat deposition in Daweishan Mini chickens.The relative expression of ADFP gene mRNA in the abdominal fat andthe liver was significantly different between 49 d and 70 d (p 0.05). The relative ApoB gene expression on 91d was higher in the liver, followed by muscles,subcutaneous fat, and abdominal fat, and was significantly higher in the liver than in the other three tissues. FATP1 gene expression in the liver presented a significant positive correlation with subcutaneous fat thickness (p 0.05). The results of this study suggest that the three genes may control the fat development in Daweishan Mini chicken(AU)

Antihyperlipidemic effect of Cyclocarya paliurus (Batal.) Iljinskaja extract and inhibition of apolipoprotein B48 overproduction in hyperlipidemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclocarya paliurus (CP) Batal., the sole species in its genus, is a native plant to China. As a traditional Chinese folk medicine, the tree leaves have been widely used for the treatment of metabolic disorders, including hyperlipidemia, obesity, diabetes and hypertension. AIM OF THE STUDY: The study aimed to evaluate the antihyperlipidemic effect of CP ethanol extract, as well as its inhibitory activity on apolipoproteinB48 (apoB48), in normal and hyperlipidemic mice. MATERIALS AND METHODS: The antihyperlipidemic effect of CP was evaluated in hyperlipidemic mice induced by high-fat diet for 4 weeks. CP ethanol extract (0.37, 0.75 and 1.5g/kg/day) was orally administrated once daily. Lipids and antioxidant profiles, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), together with the indices of hepatic and renal functions were examined. RT-qPCR and western blotting were used to analysis the expression levels of tumor necrosis factor (TNF-α), total- and triglyceride-rich apoB48 (TRL-apoB48), as well as the phosphorylation of the mitogen-activatein kinase (MAPK). RESULTS: CP as well as simvastatin remarkably lowered the levels of TC, TG, LDL-C and MDA, and at the same time, elevated the HDL-C, SOD and GSH-Px in high-fat diet mice. It also decreased the serum concentration of total- and TRL-apoB48 in the fasting state. CP inhibited TNF-α expression and phosphorylation level of MAPK. Furthermore, the HE staining of liver and kidney, together with hepatic and renal function analysis showed hepato- and renoprotective activities of CP. CONCLUSIONS: These results suggested that CP possesses beneficial potentials for use in treating hyperlipidemia and the underlying lipid-lowering mechanism might associate with a down-regulation of the intestinal-associated lipoprotein apoB48, which may provide evidence about its practical application for treating hyperlipidemia and its complications.

-LDL/ApoB-100 en niños obesos resistentes a la insulina como herramienta clínica para valorar el riesgo cardiovascular / c-LDL/ApoB-100 in insulin resistance obese children as a clinical tool for assessing cardiovascular risk / c-LDL/Apo B-100 em crianþas obesas insulino-resistentes como ferramenta clínica para avaliar o risco cardiovascular

La obesidad es la enfermedad nutricional más frecuente en niños y adolescentes en los países desarrollados. Se caracteriza por un estado proinfamatorio que supone una interrupción de las señales de traducción de la insulina con la consiguiente resistencia a la insulina. El objetivo del estudio fue valorar la presencia de factores de riesgo cardiovasculares y de partículas de c-LDL pequeñas y densas mediante el cálculo del índice c-LDL/ApoB-100 en una población infantil obesa insulinorresistente. Se incluyeron niños de ambos sexos con edades comprendidas entre 2 y 12 años que acudieron a las consultas de pediatría del Hospital Universitario Virgen Macarena. Se reclutó una cohorte de 200 niños correspondiente a un total de 97 niños y 103 niñas distribuidos en los siguientes grupos: Grupo 1: n=96 con obesidad (P97) y resistencia a la insulina (RI); y Grupo 2, n=104, con peso normal (P<80). Se calculó el per-centilo del IMC para cada edad y sexo así como se analizó el perfil lipídico y bioquímico. Ambos grupos contaron con el consentimiento informado previo a la extracción de la muestra por parte de los familiares. El cociente c-LDL/ApoB-100 alcanzó mayor significación estadística y área bajo la curva (AUC) que otros cocientes valorados, con una sensibilidad (S)=87 y especificidad (E)=0,585 para el valor de 1,3 y un AUC de 0,78 y p<0,001. Además, se obtuvo una correlación negativa entre el cociente c-LDL/ApoB-100 y el HOMA (p<0,05), el fbrinógeno (p<0,05) y us-PCR (p<0,05). El cociente c-LDL/ApoB-100 podría ser un parámetro determinante de la presencia de partículas pequeñas y densas con alta sensibilidad, significación estadística y valor predictivo positivo en una población infantil obesa e insulinorresistente como herramienta clínica para valorar el riesgo cardiovascular.(AU)

Obesity is the most common( nutritional disease in children and adolescents in developed countries. It is a proinfammatory disease that implies a break in the transduction signal of insulin with subsequent insulin resistance. The aim of the study was to assess the presence of particles of small and dense c-LDL by calculating the c-LDL/ApoB-100 index in an insulin resistant obese children population. Children of both sexes aged between 2 and 12 attending the pediatric outpatient clinics of Hospital Universitario Virgen Macarena were included. It recruited a cohort of 200 children, with a total of 103 girls and 97 boys distributed in the following groups: Group 1: n=96 obese (P97) and IR and n=104 normal weight, Group 2 (P<80). BMI percentile for age and sex as well as lipid and biochemical profle were calculated. Both groups had informed consent from relatives before the extraction. The c-LDL/ApoB-100 achieved greater statistical significance and area under the curve (AUC) than other ratios measured with sensibil-ity (S)=87 and specificity (E)=0.585 for the value of 1.3 with an AUC of 0.78 and p<0.001. Besides, a negative correlation between the c-LDL/Apo-B-100 and HOMA (p<0.05), fbrinogen (p<0.05) and us-PCR (p<0.05) ratios is obtained. The LDL/ApoB-100 ratio is a determining parameter for presence of small and dense LDL particles with high sensitivity, statistical significance and positive predictive value in an insulin resistant obese children population as a clinical tool to assess cardiovascular risk.(AU)

A obesidade é a doenþa nutricional mais comum em crianþas e adolescentes nos países desenvolvidos. Caraceriza-se por um estado pró-infamatório que sup§e uma interrupþÒo dos sinais de traduþÒo da insulina com a conseguinte resistÛncia O insulina. O objetivo do estudo foi avaliar a presenþa de fatores de risco cardiovasculares e de partículas de c-LDL pequenas e densas através do cálculodo índice c-LDL/ Apo B-100 numa populaþÒo infantil resistente O insulina. Foram incluídas crianþas de ambos os sexos com idade entre 2 e 12 anos, que foram Os consultas de pediatria do Hospital Universitário Virgem Macarena. Foi recrutado um grupo de 200 crianþas, correspondente a um total de 97 meninos e 103 meninas distribuídos nos seguintes grupos: Grupo 1: n=96 obesidade (P97) e resistÛncia O insulina (RI) e n=104 Grupo 2 de peso normal (P<80). Calculou-se o percentil do IMC para cada idade e sexo, bem como o perfil lipídico e bioquímico. Ambos os grupos tinham o consentimento informado antes da ex-traþÒo da amostra por parte da família. O quociente de c-LDL/ApoB-100 atinge significaþÒo estatística maior e área sob a curva que outros quocientes avaliados com uma sensibilidade (S)=87 e especificida-de (E)=0,585 para o valor de 1,3, e uma AUC de 0,78 e p<0,001. Além disso, foi obtida uma correla-þÒo negativa entre o quociente c-LDL/Apo-B-100 e o HOMA (p<0,05), o fbrinogÛnio (p<0,05) e us-PCR (p<0,05). O quociente c-LDL/ApoB-100 poderia ser um parÔmetro de determinaþÒo da presenþa de partículas pequenas e densas com alta sensibilidade, significaþÒo estatística e valor preditivo positivo numa populaþÒo infantil obesa e insulino-resistente como ferramenta clínica para avaliar o risco cardiovascular.(AU)

-LDL/ApoB-100 en niños obesos resistentes a la insulina como herramienta clínica para valorar el riesgo cardiovascular / c-LDL/ApoB-100 in insulin resistance obese children as a clinical tool for assessing cardiovascular risk / c-LDL/Apo B-100 em crianças obesas insulino-resistentes como ferramenta clínica para avaliar o risco cardiovascular

La obesidad es la enfermedad nutricional más frecuente en niños y adolescentes en los países desarrollados. Se caracteriza por un estado proinfamatorio que supone una interrupción de las señales de traducción de la insulina con la consiguiente resistencia a la insulina. El objetivo del estudio fue valorar la presencia de factores de riesgo cardiovasculares y de partículas de c-LDL pequeñas y densas mediante el cálculo del índice c-LDL/ApoB-100 en una población infantil obesa insulinorresistente. Se incluyeron niños de ambos sexos con edades comprendidas entre 2 y 12 años que acudieron a las consultas de pediatría del Hospital Universitario Virgen Macarena. Se reclutó una cohorte de 200 niños correspondiente a un total de 97 niños y 103 niñas distribuidos en los siguientes grupos: Grupo 1: n=96 con obesidad (P97) y resistencia a la insulina (RI); y Grupo 2, n=104, con peso normal (P<80). Se calculó el per-centilo del IMC para cada edad y sexo así como se analizó el perfil lipídico y bioquímico. Ambos grupos contaron con el consentimiento informado previo a la extracción de la muestra por parte de los familiares. El cociente c-LDL/ApoB-100 alcanzó mayor significación estadística y área bajo la curva (AUC) que otros cocientes valorados, con una sensibilidad (S)=87 y especificidad (E)=0,585 para el valor de 1,3 y un AUC de 0,78 y p<0,001. Además, se obtuvo una correlación negativa entre el cociente c-LDL/ApoB-100 y el HOMA (p<0,05), el fbrinógeno (p<0,05) y us-PCR (p<0,05). El cociente c-LDL/ApoB-100 podría ser un parámetro determinante de la presencia de partículas pequeñas y densas con alta sensibilidad, significación estadística y valor predictivo positivo en una población infantil obesa e insulinorresistente como herramienta clínica para valorar el riesgo cardiovascular.

Obesity is the most common( nutritional disease in children and adolescents in developed countries. It is a proinfammatory disease that implies a break in the transduction signal of insulin with subsequent insulin resistance. The aim of the study was to assess the presence of particles of small and dense c-LDL by calculating the c-LDL/ApoB-100 index in an insulin resistant obese children population. Children of both sexes aged between 2 and 12 attending the pediatric outpatient clinics of Hospital Universitario Virgen Macarena were included. It recruited a cohort of 200 children, with a total of 103 girls and 97 boys distributed in the following groups: Group 1: n=96 obese (P97) and IR and n=104 normal weight, Group 2 (P<80). BMI percentile for age and sex as well as lipid and biochemical profle were calculated. Both groups had informed consent from relatives before the extraction. The c-LDL/ApoB-100 achieved greater statistical significance and area under the curve (AUC) than other ratios measured with sensibil-ity (S)=87 and specificity (E)=0.585 for the value of 1.3 with an AUC of 0.78 and p<0.001. Besides, a negative correlation between the c-LDL/Apo-B-100 and HOMA (p<0.05), fbrinogen (p<0.05) and us-PCR (p<0.05) ratios is obtained. The LDL/ApoB-100 ratio is a determining parameter for presence of small and dense LDL particles with high sensitivity, statistical significance and positive predictive value in an insulin resistant obese children population as a clinical tool to assess cardiovascular risk.

A obesidade é a doença nutricional mais comum em crianças e adolescentes nos países desenvolvidos. Caraceriza-se por um estado pró-infamatório que supõe uma interrupção dos sinais de tradução da insulina com a conseguinte resistência à insulina. O objetivo do estudo foi avaliar a presença de fatores de risco cardiovasculares e de partículas de c-LDL pequenas e densas através do cálculodo índice c-LDL/ Apo B-100 numa população infantil resistente à insulina. Foram incluídas crianças de ambos os sexos com idade entre 2 e 12 anos, que foram às consultas de pediatria do Hospital Universitário Virgem Macarena. Foi recrutado um grupo de 200 crianças, correspondente a um total de 97 meninos e 103 meninas distribuídos nos seguintes grupos: Grupo 1: n=96 obesidade (P97) e resistência à insulina (RI) e n=104 Grupo 2 de peso normal (P<80). Calculou-se o percentil do IMC para cada idade e sexo, bem como o perfil lipídico e bioquímico. Ambos os grupos tinham o consentimento informado antes da ex-tração da amostra por parte da família. O quociente de c-LDL/ApoB-100 atinge significação estatística maior e área sob a curva que outros quocientes avaliados com uma sensibilidade (S)=87 e especificida-de (E)=0,585 para o valor de 1,3, e uma AUC de 0,78 e p<0,001. Além disso, foi obtida uma correla-ção negativa entre o quociente c-LDL/Apo-B-100 e o HOMA (p<0,05), o fbrinogênio (p<0,05) e us-PCR (p<0,05). O quociente c-LDL/ApoB-100 poderia ser um parâmetro de determinação da presença de partículas pequenas e densas com alta sensibilidade, significação estatística e valor preditivo positivo numa população infantil obesa e insulino-resistente como ferramenta clínica para avaliar o risco cardiovascular.

Favorable effects of ezetimibe alone or in association with simvastatin on the removal from plasma of chylomicrons in coronary heart disease subjects.

OBJECTIVE: Reductions on the clearance from plasma of chylomicrons are associated with atherosclerosis. Statins improve the removal from plasma of chylomicrons in a dose dependent manner. There is controversy whether ezetimibe modifies the plasma clearance of chylomicrons. Effects of ezetimibe alone or in combination with simvastatin were compared with low and high dose of the latter, upon the kinetics of a chylomicron-like emulsion in coronary heart disease (CHD) patients. METHODS: 25 CHD patients were randomized for treatment with ezetimibe 10 mg (group 1) or simvastatin 20 mg (group 2) with progression to ezetimibe + simvastatin 10/20 mg or simvastatin 80 mg, respectively. Kinetic studies were performed at baseline and after each treatment period of 6 weeks. The fractional catabolic rates (FCR) of the emulsion labeled with (14)C-CE and (3)H-TG, that represent respectively chylomicron remnant and triglyceride removal, were calculated. Comparisons were made by ANOVA. RESULTS: The (14)CE-FCR in group 1 were 0.005 ± 0.004, 0.011 ± 0.008 and 0.018 ± 0.005 min(-1) and in group 2 were 0.004 ± 0.003, 0.011 ± 0.008 and 0.019 ± 0.007 min(-1) respectively at baseline, after 6 and 12 weeks (p < 0.05 vs. baseline, and 6 vs. 12 weeks). The (3)H-TG-FCR in group 1 were 0.017 ± 0.011, 0.024 ± 0.011 and 0.042 ± 0.013 min(-1) and in group 2 were 0.016 ± 0.009, 0.022 ± 0.009 and 0.037 ± 0.012 min(-1) at baseline, after 6 and 12 weeks (p < 0.05 vs. baseline, and 6 vs. 12 weeks). There were no differences between groups in time. CONCLUSION: Both treatments increased similarly the removal from plasma of chylomicron and remnants in CHD patients.