Cell cholesterol esters and high-density lipoprotein plasma levels during liver hyperplasia in choline-fed male and female rats

Sexual dimorphism exists in the response of rats to lead nitrate, liver hyperplasia occuring earlier and being more pronounced in males. Excess dietary choline in females shifted the growth pattern towards that of males. To determine whether phosphatidylcholine-induced growth modulations could be related to a derangement of cholesterol metabolism, liver accumulation of cholesterol esters and plasma lipoprotein patterns were investigated. In males, lead-induced liver hyperplasia was associated with increased total cholesterol hepatic content, accumulated cholesterol esters and reduced concentration of plasma High Density Lipoprotein (HDL) cholesterol. Females were less responsive to the liver mitogenic signal of lead nitrate; there was no elevation of cholesterol content nor any marked accumulation of cholesterol esters. This is consistent with the lack of change in the plasma levels of HDL cholesterol. Continuous choline feeding displaced the liver cholesterol ester pattern and plasma HDL cholesterol levels in females, and in parallel that of DNA synthesis, towards those of males. Choline was not observed to have any effect in males. These results suggest that the derangement of phosphatidylcholine metabolism induces growth-related changes in cholesterol turnover; they are consistent with the proposal that the intracellular content of cholesterol esters may have a role in regulating liver growth rates.     

Behavior of 3-year-old children in a prospective randomized trial of reduced saturated fat and cholesterol diet since infancy: The strip baby project

Interventions aimed at decreased exposure of children to known atherosclerosis risk factors may have untoward behavioral side effects. We examined how children’s behavior or parent’s perception of the behavior of the children at 3 years of age was influenced by the intervention in a prospective randomized trial that began in infancy and effectively decreased scrum cholesterol concentration. This Special Turku coronary Risk factor Intervention Project for babies (STRIP) began when the infant was 7 months old. Half of 1.062 children received individualized dietary counseling at 1-to 3-month intervals during the first 2 years of age and then half-yearly; the other half had an unrestricted diet. At 3 years of age a standardized questionnaire of the child’s behavior was sent to 791 families (76% returned the questionnaire). At the onset of the trial the sociodemographic data of the families and scrum lipid values of the intervention and control children were similar. Later, mean serum cholesterol values of the intervention children remained constantly at a level 6% to 10% below the values of the control children. At 3 years of age the parental perceptions of the child’s behavior suggested minimal differences between the intervention and control children. The intervention children were slightly less jealous and more active and creative, but showed slightly more negative signs of behavior (bed-wetting, problems in falling asleep, fears) than the controls. We conclude that long-term, individualized dietary and lifestyle intervention that begins in infancy slightly influences children’s behavior or parent’s recognition of the behavior of the children at the age of 3 years. This work was supported in part by grants from the Varsinais-Suomi Regional Fund of the Finnish Cultural Foundation, the Mannerheim League for Child Welfare, the Academy of Finland, and the Alli Paasikivi Foundation.     

Holoprosencephaly: from Homer to Hedgehog

Holoprosencephaly (HPE), a common developmental defect affecting the forebrain and face, is etiologically heterogeneous and exhibits wide phenotypic variation. Graded degrees of severity of the brain malformation are also reflected in the highly variable craniofacial malformations associated with HPE. In addition, individuals with microforms of HPE, who usually have normal cognition and normal brain imaging, are at risk for having children with HPE. Some obligate carriers for HPE may not have any phenotypic abnormalities. Recurrent chromosomal rearrangements in individuals with HPE suggest loci containing genes important for brain development, and abnormalities in these genes may result in HPE. Recently, Sonic Hedgehog (SHH) was the first gene identified as causing HPE in humans. Proper function of SHH depends on cholesterol modification. Other candidate genes that may be involved in HPE include components of the SHH pathway, elements involved in cholesterol metabolism, and genes expressed in the developing forebrain.     

1990—2019年中国高血清低密度脂蛋白胆固醇疾病负担趋势分析与预测

目的 描述和分析1990—2019年中国高血清低密度脂蛋白胆固醇（high LDL cholesterol,高LDL - C）疾病负担状况及变化趋势,并预测未来5年的疾病负担,为中国高LDL - C科学防控提供依据。方法 提取2019年全球疾病负担（GBD 2019）中因高LDL - C造成的死亡数、死亡率及DALYs等疾病负担指标,相关指标均采用GBD 2019全球标准人口进行年龄标准化,采用平均年度变化百分比（AAPC）分析率的变化趋势,并应用R 4.1.0对1990—2016年中国因高LDL - C造成的死亡率和DALYs率建立ARIMA模型和NNAR模型,用2017—2019年的数据来评价两模型的拟合效果,最后用拟合效果最好的模型预测2020—2024年中国高LDL - C死亡率和DALYs率。结果 1990—2019年中国高LDL - C造成的死亡率（AAPC = 3.1%,P＜0.05）和DALYs率（AAPC = 2.2%,P＜0.05）整体呈波动上升趋势;标化死亡率和DALYs率增长14.21%和0.56%,男女性别比范围分别为1.33～1.67和1.36～1.76,男性高于女性;年龄别疾病负担≥70岁人群远高于15～49岁和50～69岁群体;ARIMA（0,2,0）和NNAR（1,1）模型预测与实际趋势基本一致,前者预测值与实际值相对误差、均方根误差（RMSE）、平均绝对误差（MAE）以及平均绝对百分误差（MAPE）均较小,预测精度更好。 结论 中国高LDL - C造成的疾病负担呈逐渐上升趋势,在2020—2024年将继续上升。男性、高龄人群疾病负担更加沉重,应采取针对性措施进行干预。     

阿托伐他汀与辛伐他汀治疗高脂血症的效果

目的分析在高脂血症患者治疗中应用阿托伐他汀和辛伐他汀的降脂效果。方法将2017年1月—2020年1月在我院医治的90例高脂血症患者随机设为两个组别,给予对照组(45例)辛伐他汀治疗,给予试验组(45例)阿托伐他汀治疗。观察两组患者治疗前后血脂水平和生化指标变化情况。结果试验组治疗后总胆固醇、三酰甘油、低密度脂蛋白胆固醇低于对照组,高密度脂蛋白胆固醇高于对照组,两组对比差异具有统计学意义(P<0.05)。两组患者治疗后肌酐、尿素氮指标差异无统计学意义(P>0.05)。结论阿托伐他汀和辛伐他汀应用于高脂血症患者治疗中均能起到不同程度的降脂效果,但阿托伐他汀的效果更好,安全可靠。     

Effects of Late-Life Caloric Restriction on Age-Related Alterations in the Rat Cortex and Hippocampus

Background: A major problem of aging is the disruption of metabolic homeostasis. This is particularly relevant in the brain where it provokes neurodegeneration. Caloric restriction is a physiologic intervention known to delay the deleterious consequences of aging in several species ranging from yeast to mammals. To date, most studies on experimental models have started this dietary intervention from weaning, which is very difficult to be translated to human beings. Here, we study the effects of a more realistic dietary regimen in rats, starting at an advanced age and lasting for six months. Methods: we analyzed in the cortex and hippocampus, the proteins involved in the energetic balance of the cells, cholesterol metabolism, oxidative stress response, inflammation, synaptic impairment, and brain trophism. Results: our results suggest that caloric restriction in late life can revert only some age-related changes studied here.     

Associations between Circulating Markers of Cholesterol Homeostasis and Macrovascular Events among Patients Undergoing Hemodialysis

Current strategies targeting serum cholesterol bring limited benefits to mortality and macrovascular events prevention among hemodialysis patients. Direct measurements and analysis on circulating markers of cholesterol homeostasis could be promising solutions to this bottleneck. We prospectively enrolled 90 maintenance hemodialysis patients and 9 healthy controls in 2019 for 1 year. We measured circulating desmosterol and lathosterol as markers for cholesterol synthesis and campesterol and sitosterol for cholesterol absorption. At baseline, hemodialysis patients showed higher levels of campesterol (p = 0.023) compared to healthy controls. During follow-up, we identified 14 (15.4%) patients who experienced macrovascular events. Comparisons of cholesterol homeostasis markers between cohorts with and without macrovascular events showed no significant differences in markers of cholesterol synthesis or absorption. Using logistic regression analysis, the odds ratio was not statistically significant for the prediction of macrovascular events after full-adjusting for age, sex, diabetes, serum albumin, cholesterol, and triglyceride. We concluded that hemodialysis patients demonstrated higher level of cholesterols absorption, indicated by circulating campesterol compared to healthy subjects. Markers for cholesterol homeostasis were not significantly associated with macrovascular events during a 1-year follow-up. Our results shed light on the novel therapeutic target of modulating cholesterol absorption in HD patients.     

Chronic Intake of Energy Drinks and Their Sugar Free Substitution Similarly Promotes Metabolic Syndrome

Energy drinks containing significant quantities of caffeine, taurine and sugar are increasingly consumed, particularly by adolescents and young adults. The putative effects of chronic ingestion of either standard energy drink, Mother^TM (ED), or its sugar-free formulation (sfED) on metabolic syndrome were determined in wild-type C57BL/6J mice, in comparison to a soft drink, Coca-Cola (SD), a Western-styled diet enriched in saturated fatty acids (SFA), and a combination of SFA + ED. Following 13 weeks of intervention, mice treated with ED were hyperglycaemic and hypertriglyceridaemic, indicating higher triglyceride glucose index, which was similar to the mice maintained on SD. Surprisingly, the mice maintained on sfED also showed signs of insulin resistance with hyperglycaemia, hypertriglyceridaemia, and greater triglyceride glucose index, comparable to the ED group mice. In addition, the ED mice had greater adiposity primarily due to the increase in white adipose tissue, although the body weight was comparable to the control mice receiving only water. The mice maintained on SFA diet exhibited significantly greater weight gain, body fat, cholesterol and insulin, whilst blood glucose and triglyceride concentrations remained comparable to the control mice. Collectively, these data suggest that the consumption of both standard and sugar-free forms of energy drinks induces metabolic syndrome, particularly insulin resistance.     

Maternal Quercetin Consumption during Pregnancy May Help Regulate Total Cholesterol/HDL-Cholesterol Ratio without Effect on Cholesterol Levels in Male Progeny Consuming High-Fat Diet

Quercetin has been shown to have anti-obesity effects, but it is unknown whether these effects can be transmitted from mothers to their progeny. In this study, we investigated whether maternal quercetin consumption during pregnancy has a protective effect on high-fat diet–induced hyper lipid levels and overweight in progeny. Female mice consumed a control diet or a diet containing 1.0% quercetin during breeding. The male progeny were then divided into four groups that were (1) sacrificed at postnatal day 3; (2) born to dams fed the control diet and also fed the control diet (C-C), (3) born to dams fed the control diet and then fed a 30% high-fat diet (C-HF), or (4) born to dams fed the Q-diet and then fed the HF diet (Q-HF). Maternal consumption of quercetin did not affect body weight or blood lipid parameters in either dams or neonates at postnatal day 3. After 13 weeks, the Q-HF group exhibited greater body and liver weights, and higher blood cholesterol levels than the C-HF group. However, the total cholesterol/ high density lipoprotein (HDL)-cholesterol ratios in the Q-HF and C-C groups remained similar. In conclusion, maternal quercetin consumption does not appear to protect the next generation from high-fat diet–induced hyper cholesterol level in the blood and liver, and consequently overweight, but may help regulate the total cholesterol/HDL-cholesterol ratio.     

In Vivo Evaluation of Dendropanax morbifera Leaf Extract for Anti-Obesity and Cholesterol-Lowering Activity in Mice

Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg⁻¹∙d⁻¹ had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg⁻¹∙d⁻¹. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.