A descriptive analysis of hyperlipidemia in adult twins in China / 中华流行病学杂志

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.

Difference of lipid-lowering efficacy of "Xinjianqu" before and after fermentation and its mechanism based on LKB1-AMPK pathway and 16S rDNA sequencing technology / 中国中药杂志

On the basis of establishing the prescription of Xinjianqu and clarifying the increase of the lipid-lowering active ingredients of Xinjianqu by fermentation, this paper further compared the differences in the lipid-lowering effects of Xinjianqu before and after fermentation, and studied the mechanism of Xinjianqu in the treatment of hyperlipidemia. Seventy SD rats were randomly divided into seven groups, including normal group, model group, positive drug simvastatin group(0.02 g·kg~(-1)), and low-dose and high-dose Xinjianqu groups before and after fermentation(1.6 g·kg~(-1) and 8 g·kg~(-1)), with ten rats in each group. Rats in each group were given high-fat diet continuously for six weeks to establish the model of hyperlipidemia(HLP). After successful modeling, the rats were given high-fat diet and gavaged by the corresponding drugs for six weeks, once a day, to compare the effects of Xinjianqu on the body mass, liver coefficient, and small intestine propulsion rate of rats with HLP before and after fermentation. The effects of Xinjianqu before and after fermentation on total cholesterol(TC), triacylglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), creatinine(Cr), motilin(MTL), gastrin(GAS), and the Na~+-K~+-ATPase levels were determined by enzyme-linked immunosorbent assay(ELISA). The effects of Xinjianqu on liver morphology of rats with HLP were investigated by hematoxylin-eosin(HE) staining and oil red O fat staining. The effects of Xinjianqu on the protein expression of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), liver kinase B1(LKB1), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase(HMGCR) in liver tissues were investigated by immunohistochemistry. The effects of Xinjianqu on the regulation of intestinal flora structure of rats with HLP were studied based on 16S rDNA high-throughput sequencing technology. The results showed that compared with those in the normal group, rats in the model group had significantly higher body mass and liver coefficient(P<0.01), significantly lower small intestine propulsion rate(P<0.01), significantly higher serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2(P<0.01), and significantly lower serum levels of HDL-C, MTL, GAS, Na~+-K~+-ATP levels(P<0.01). The protein expression of AMPK, p-AMPK, and LKB1 in the livers of rats in the model group was significantly decreased(P<0.01), and that of HMGCR was significantly increased(P<0.01). In addition, the observed＿otus, Shannon, and Chao1 indices were significantly decreased(P<0.05 or P<0.01) in rat fecal flora in the model group. Besides, in the model group, the relative abundance of Firmicutes was reduced, while that of Verrucomicrobia and Proteobacteria was increased, and the relative abundance of beneficial genera such as Ligilactobacillus and Lachnospiraceae＿NK4A136＿group was reduced. Compared with the model group, all Xinjianqu groups regulated the body mass, liver coefficient, and small intestine index of rats with HLP(P<0.05 or P<0.01), reduced the serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2, increased the serum levels of HDL-C, MTL, GAS, and Na~+-K~+-ATP, improved the liver morphology, and increased the protein expression gray value of AMPK, p-AMPK, and LKB1 in the liver of rats with HLP and decreased that of LKB1. Xinjianqu groups could regulate the intestinal flora structure of rats with HLP, increased observed＿otus, Shannon, Chao1 indices, and increased the relative abundance of Firmicutes, Ligilactobacillus(genus), Lachnospiraceae＿NK4A136＿group(genus). Besides, the high-dose Xinjianqu-fermented group had significant effects on body mass, liver coefficient, small intestine propulsion rate, and serum index levels of rats with HLP(P<0.01), and the effects were better than those of Xinjianqu groups before fermentation. The above results show that Xinjianqu can improve the blood lipid level, liver and kidney function, and gastrointestinal motility of rats with HLP, and the improvement effect of Xinjianqu on hyperlipidemia is significantly enhanced by fermentation. The mechanism may be related to AMPK, p-AMPK, LKB1, and HMGCR protein in the LKB1-AMPK pathway and the regulation of intestinal flora structure.

Improvement effect and mechanism of ethanol extract from Citri Reticulatae Pericarpium on triglyceride in hyperlipidemia model rat / 中国中药杂志

The aim of this paper was to study the improvement effect of ethanol extract from Citri Reticulatae Pericarpium(CRP) on triglyceride of hyperlipidemia model rats, and to explore the possible mechanism. SD rats were randomly divided into normal group, model group, positive control group, and high, medium and low-dose CRP ethanol extract groups, with 10 rats in each group. During the experiment, except for the normal group that was fed with distilled water and ordinary feed, rats in the other groups were given different concentrations of alcohol and fed with high-sugar and fat diets. All rats were given free diets. While being modeled, each group was administered with 0.01 mL·g~(-1) by gavage once a day for six weeks. Blood samples were collected after two weeks, four weeks and six weeks of drug treatment. After the completion of the experiment, blood, liver and adipose tissue were collected. Triglyceride(TG), alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP) in serum, TG in liver tissue and TG in fecal were detected. Free fatty acid(FFA) and triglyceride-related hydrolase, such as adipose tiglyceride lipase(ATGL), lipoprotein lipase(LPL), hepatic lipase(HL), hormone-sensitive triglyceride lipase(HSL) were detected by ELISA. The mRNA expressions of peroxisome proliferators-activated receptors(PPARγ), sterol regulatory element binding protein 1 c(SREBP-1 c) and farnesoid X receptor(FXR) were determined by RT-PCR. Compared with the model group, each administration group could reduce TG levels in serum and liver to varying degrees, reduce serum ALT, AST, ALP activities, significantly reduce free fatty acid content in serum, significantly increase triglyceride metabolism-related enzymes, including fat ATGL, LPL and liver HL content, and significantly reduced the content of fat HSL. According to the study of transcriptional regulation genes relating to triglyceride metabolism, extract from CRP could significantly increase the mRNA expressions of PPARγ and FXR. In conclusion, ethanol extract from CRP could ob-viously reduce the TG level of hyperlipidemia model rats, and might reduce plasma TG content by increasing PPARγ-LPL/ATGL and FXR-HL triglyceride hydrolysis pathways.

Study on lipid-lowering mechanism of active peptide DP17 from Eupolyphaga steleophaga in hyperlipidemia rats / 中国中药杂志

The aim of this paper was to investigate the mechanism of the active peptide DP17 of Eupolyphaga steleophaga in the treatment of hyperlipidemia rats. HPLC and MADIL-TOF/TOF-MS were used for the amino acid sequence analysis and solid-phase synthesis on the active peptide of E. steleophaga which were obtained by biomimetic enzymatic hydrolysis, separation and purification. The hyperlipidemia model was established by feeding with high-fat diet.Twenty days later, the rats in the blank group and the model group were given the saline and the rats in remaining groups were given the corresponding drugs by oral administration. After administration for 4 weeks, the levels of triglyceride(TG), total cholesterol(TC) and low density lipoprotein(LDL) in serum, the levels of TG, TC, adenosine monophosphate(AMP), adenosine triphosphate(ATP) in liver tissues and TG in feces were detected, respectively. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of liver tissues. The Real-time fluorescence quantitative PCR method was used to detect the expression of acetyl coa carboxylase(ACC) and hydroxymethylglutaryl-coa reductase(HMGCR) mRNA in liver tissues. The expression of mammalian target of rapamycin(mTORC1) protein and adenosine 5'-monophosphate-activated protein kinase(AMPK) in liver tissues were detected by Western blot. The analysis showed that the amino acid sequence of active peptide from E. steleophaga was DAVPGAGPAGCHPGAGP(DP17). The results of pharmacological experiments showed that after oral administration of DP17 in rats, the levels of TG, TC and LDL in serum as well as TG and TC levels in liver tissues were significantly decreased(P<0.05), while the levels of AMP, ATP in liver tissues and TG content in feces were significantly increased(P<0.05); the liver steatosis of rats was significantly relieved; the expression of ACC, HMGCR mRNA and mTORC1 protein in liver tissues were significantly reduced, while the expression of AMPK phosphorylated protein was significantly increased(P<0.05). DP17, the active peptide of E. steleophag can significantly reduce lipid accumulation in liver tissues, and it may play a role in reducing blood lipids by regulating the energy metabolism balance in the body and activating AMPK/mTOR signaling pathway.

Association between polymorphisms in the APOB gene and hyperlipidemia in the Chinese Yugur population

We investigated the influence of apolipoprotein B gene (APOB) variants on the risk of hyperlipidemia (HL) in 631 middle-aged and elderly members of the Chinese Yugur population (HL, n=336; normolipidemia, n=295). APOB polymorphisms were identified using mass spectrometry, and five single nucleotide polymorphisms (rs1042034, rs2163204, rs512535, rs676210, and rs679899) and serum lipids were further analyzed. rs1042034 and rs676210 were significantly associated with HL (P<0.05). Compared with the GG or AA genotype, individuals with AG and AG+AA in rs1042034 and with AG and AG+GG in rs676210 had a 1.67-fold (95%CI=1.20-2.33),1.63-fold (95%CI=1.19-2.24), 1.72-fold (95%CI=1.24-2.40), and 1.67-fold (95%CI=1.21-2.291) increased risk of high HL, respectively. rs2163204 was in strong linkage disequilibrium with rs1042034, rs676210, and rs679899, and strong disequilibrium was observed between rs1042034 and rs676210 (D′>0.9). Compared with the GTGAA haplotype, haplotypes ATGGA and ATAGG were more strongly associated with HL [odds ratio (OR)=1.46, 95%CI=0.02-2.11; OR=1.63, 95%CI=1.03-2.60, respectively]. The risk factors age (P=0.008), body mass index (P<0.0001), GA+GG genotype in rs676210 (P=0.009), and alcohol consumption (P=0.056) contributed strongly to HL development. The A allele of rs1042034 and the G allele of rs676210 may thus predispose middle-aged and elderly members of the Chinese Yugur population to HL in combination with other genetic or nutritional factors, and could be used as new genetic markers for HL screening.

Genetic & epigenetic approach to human obesity.

Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS) have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12th update of Human Obesity Gene Map there are 253 quantity trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

Study of XmnI polymorphism in 5 region of the apoAl gene in Iranian hyperlipidemic subjects

Several studies have demonstrated the relationship between polymorphisms in the ApoAl - CIH - AIV gene cluster and hyperlipidemia. This study was conducted to elucidate the association between polymorphism of ApoAI/XmnI and Iranian hyperlipidemic subjects. Total genomic DNA was prepared from seventy-six Iranian patient with primary hyperlipidemia and seventy-five normolipidemic subjects. The subjects in the control group were age-and sex-matched to the patients. Fragment of 392 bp for 5 region of the apoAl gene [C-2500T] was amplified by polymerase chain reaction [PCR]. In the hyperlipidemic group, the genotype frequency of X1X1, X1X2, X2X2 were 0.63, 0.24, 0.13, respectively. In the control group those were 0.81, 0.11 and 0.08, respectivley. There was a significant difference [p<0.05] between 2 groups. The rare allele [X2] was more frequent in hyperlipidemic group than in controls [p<0.01]. Various genotypes of apoAl/Xmnl had no significant effect on lipids or apoAI levels in hyperlipidemic group. The above results show that polymorphism ApoAl/XmnI is associated with hyperlipidemia in Iranian hyperlipidemic subjects. Therefore, our data confirmed the previously reported association between genetic polymorphism ApoAI/XmnI and hyperlipidemia

Apolipoprotein E polymorphism and coronary heart disease.

Apolipoprotein E is a constituent of various lipoproteins and plays an important role in the transport of cholesterol and other lipids among cells of various tissues. The gene is polymorphic with three alleles (epsilon2, epsilon3, and epsilon4) coding for isoforms E2, E3, and E4 and having different binding affinities for the apo E receptors. While the epsilon2 allele is associated with elevated triglyceride levels, epsilon4 allele is associated with increased cholesterol levels. Though several studies support the role of apo E polymorphism in CHD either directly or indirectly via its influence on lipid and lipoprotein levels, there are some studies, which show no association. With the increasing incidence of CHD among Indians, it becomes imperative to identify genetic markers that may predispose individuals to coronary events. It would be of importance to determine if apo E gene will become a usefuladjunct to assess cardiovascular risk profile when performing genetic studies in families.

Dislipidemias / Dyslipidemias

Os autores salientam o interesse das dislipidemias nos últimos anos, mencionando estudos que demonstram redução da mortalidade total, da prevenção primária e secundária, bem como de acidentes vasculares cerebrais, mencionado as mais recentes diretrizes e recomendações. Apresentam o diagnóstico clínico e laboratorial das dislipidemias e todas as recomendações específicas para a determinação do perfil lipídico, demonstrando os valores de referência, de acordo com as últimas diretrizes. Mencionam a importância da diferenciação das hiperlipidemias primárias e secundárias (hipotireoidismo, síndrome nefrótica, diabetes, obesidade, icterícia obstrutiva, alcoolismo e insuficiência renal crônica e por medicamentos)...

Importância das dislipidemias em Pediatria / Importance of the dyslipidemias inPediatrics

Enfatizando a importância das dislipidemias na infância, em funçäo de suas consequências na idade adulta, os autores classificam as alteraçöes do perfil lipídico, descrevem a evoluçäo da aterosclerose, detêm-se particularmente no quadro clínico das dislipidemias primárias e secundárias a outras patologias, estudam seu diagnóstico e apresentam recomendaçöes gerais relativas à sua prevençäo e terapêutica

Dyslipidaemias in white normotensive subjects and in white patients treated for essential hypertension

Foram analisados os perfis lipidicos sericos de 143 hipertensos essenciais tratados (HT: 31 homens, 112 mulheres, idade media 58,4+-0,9 anos) e de 54 normotensos (NT: 15 homens, 39 mulheres, 56,7+-1,8 anos) sendo ambos os grupos da raca branca...

La obesidad como factor de riesgo cardiovascular en México: estudio en población abierta / Obesity as a cardiovascular riks factor in Mexico: a population based study

Se presentan los resultados de una investigación, realizada en población abierta urbana de nivel económico bajo, diseñada para estimar la prevalencia de obesidad, caracterizar sus variantes de distribución de adiposidad corporal, y evaluar el impacto que tiene sobre las variables metabólicas que definen el riesgo cardiovascular. El estudio se realizó en una colonia del distrito Federal. El censo de la comunidad reveló una población total de 4411 bhabitantes, de los cuales 931 se encontraron entre 35 y 64 años (452 hombres, 479 mujeres) que se consideraron elegibles. Las tasas de respuesta fueron: en la entrevista de domicilio 92 por ciento, y en el examen físico 70 por ciento. Utilizando como indicador de adiposidad corporal el índice de masa corporal (IMC), definiendo obesidad a partir de un IMC en hombres * 27.7 y en mujeres * 27.3, encontramos una tasa cruda de prevalencia de 37 por ciento en los hombres y en las mujeres de 60 por ciento. los pliegues subescapular y tricipital tuvieron valores significativamente más altos en los sujetos obesos. La relación entre las circunferencias de cintura y cadera reveló un acúmilo de adiposidad en el segmento superior del cuerpo especialmente mayor en los dos primeros grupos de edad en ambos sexos. La presión arterial fue más alta en los sujetos obesos siendo significativa la diferencia en los hombres de los primeros dos grupos de edad y en las mujeres más jóvenes. Los valores de glucemia postcarga de glucosa fueron significativamente más altos en los primeros dos grupos de edad en las mujeres y en los hombres del grupo intermedio con diagnóstico de obesidad. Los valores de insulina en ayuno fueron significativamente más altos en los primeros dos grupos de edad en los hombres y en los tres de las mujeres. Se demostró un nivel bajo de HDL colesterol en toda la población. Esta diferencia alcanzó significancia en las mujeres jóvenes. Resalta la hipertrigliceridemia que se encontró en la mayor parte de la población con y sin obesidad. La opinión de los participantes fue explorada: se observó que los hombres tienden a preferir intentar bajar de peso con ejercicio, y la mujer con dieta. Una proporción importante de la población admite haber subido de peso con la edad y considera que el ejercicio no sirve para bajar de peso, ya que éste aumenta el apetito. Concluimos que la obesidad es un grave problema de salud pública que afecta una parte muy grande de la población. Este problema tiende a incrementarse entre otras caus

Apolipoprotein E genotypes of normal and hyperlipidemic subjects

Apolipoprotein E (apo E) plays a role in the regulation of the lipid metabolism of humans. Apo E, 229 amino acid polypeptide, is classified into three major isoform (E2, E3, E4) according to the differences of amino acid in position 112 and 158. In the normal population apo E3 isoform is most prevalent and apo E2 or E4 is frequently associated with hyperlipoproteinemia. To find out the frequency of apo E isoform distribution in the Korean population, apo E genotyping was performed. After amplification of apoE gene by polymerase chain reaction (PCR), restriction isotyping was done by cleavage with restriction enzyme Hha I and polyacrylamide gel electrophoresis. The apo E allele frequency in 73 normal subjects was 4.8% for E2, 84.9% for E3 and 10.3% for E4. In diabetic patient with hyperlipoproteinemia, the frequency of apo E allele was 6.3% for E2, 81.0% for E3 and 12.7% for E4. There was no significant difference in apo E isoform distribution between diabetics and normal populations. But in patients with cardiovascular disease with hyperlipidemia, the apo E4 allele frequency was significantly higher than normal (20.0% vs 10.3%, p<0.005). Apo E3 was the most common isoform in normal and diabetic subjects and apo E2 isoform was rather low frequency compared to Caucasians. This pattern is similar to the Japanese population but somewhat different from other populations. From the data of a high association of apo E4 allele and cardiovascular disease with hypercholesterolemia, apo E isoform may be one of the determinants of hyperlipoproteinemia. The PCR method may be useful in apo E genotyping.

Sindrome de Lipodistrofia Congénita Generalizada / Congenital generalized lipodystrophy syndrome

El actual estudio trata sobre la forma de presentación y evolución de los pacientes con lipodistrofia congénita generalizada o el Síndrome de Seip-Berardinelli. Se caracteriza por la ausencia de tejido graso subcutáneo, cirrosis hepática, desarrollo de diabetes resistente a la insulina, hiperlipemia, y crecimiento corporal rápido con edad ósea avanzada en la infancia, coexistiendo alteraciones cutáneas, desarrollo muscular exagerado y compromiso de otros órganos. Se presentan 3 casos de esta patología diagnosticados entre 9 y 19 meses de edad. Las 3 pacientes presentaban varias características en común: aparentaban una edad mayor a la cronlógica, cara triangular, abundante cabello, lesiones hiperpigmentadas a predominio de pliegues, marcada disminución de tejido celular subcutáneo, prominencia muscular y hepatomegalia. Otros hallazgos clínicos sólo se demostraron en una u otra de las pacientes. La evaluación de laboratorio muestra alteración precoz de lípidos a predominio de triglicéridos, conservando la glicemia y la curva de tolerancia a la glucosa dentro de límites normales. Edad ósea avanzada en 1 de los 3 casos. Analizando los datos de las pacientes y de la literatura respecto a la fisiopatología y posibles efectos beneficiosos de los neurolépticos, se sugiere existencia de alguna anomalía a nivel del hipotálamo y/o hipófisis responsable de la presentacióm del cuadro clínico.