Higher Plasma Total Cholesterol Research Articles

Hif-1α expression targets the TMA/Fmo3/TMAO axis to participate in gallbladder cholesterol stone formation in individuals living in plateau regions

The incidence of gallbladder cholesterol stones (GCS) increases rapidly among people living in high-altitude hypoxic environments compared to those in normoxic areas. Upregulation of hepatic hypoxia inducible factor 1α (Hif-1α) plays a key role in the formation of GCS. High plasma trimethylamine-N-oxide (TMAO) levels are positively correlated with the occurrence of GCS. We hypothesized that HIF-1α may upregulate TMAO levels by promoting the transcription of flavin-containing monooxygenase 3 (Fmo3), which eventually leads to GCS formation. Our study shows that in women, high plasma total cholesterol and apolipoprotein B were positively correlated with cholecystolithiasis and hypoxia. Hif-1α binds to the Fmo3 promoter and promotes Fmo3 expression. Hypoxia and lithogenic diet induce the expression of Hif-1α, Fmo3, TMAO and cholesterol tube transporters in the livers of mice, disturb the proportion of bile and plasma components, and induce the formation of GCS. In cell experiments, silencing Hif-1α downregulates the expression of Fmo3, TMAO and cholesterol tube transporters. In a mouse model of hypoxic cholecystolithiasis, silencing Hif-1α downregulates the expression of related genes, restores the proportion of bile and plasma lipid components, and reduces the formation of GCS. Our study shows that Hif-1α binds to the promoter region of Fmo3 and promotes Fmo3 transcription. Thus, it mediates the transcriptional activation of the TMA/Fmo3/TMAO pathway, upregulates the expression of ATP-binding cassettes (Abc) g5 and g8, and participates in the regulation of the occurrence of GCS in the plateau region.

Reduction of lauric acid content in virgin coconut oil improved plasma lipid profile in high-fat diet-induced hypercholesterolemic mice.

Virgin coconut oil (VCO) is claimed to have various health benefits, but favorable effects of its major component (∼50%), lauric acid, are controversial. Therefore, we aimed to reduce lauric acid content (∼30%) in VCO and evaluate its effect compared to VCO and medium-chain triglycerides (MCT), on food intake, bodyweight (BW), lipid profiles, and hepatic histology. Female C57BL/6 mice were treated with different diets for 3 months: control (normal diet), high-fat diet (HF), HF+VCO, HF+MCT, HF+low lauric acid VCO (LLA), and normal diet+LLA (C+LLA). LLA was prepared by enzymatic interesterification of VCO with methyl octanoate (methyl caprylate) and methyl decanoate (methyl caprate). Plasma and liver lipids, including total cholesterol (TC), high-density lipoprotein (HDL), and triglyceride, were measured by colorimetric assay, and hepatic fat accumulation was examined by oil-red-O staining. HF mice exhibited high plasma and liver TC and low-density lipoprotein (LDL). VCO or MCT treatment lowered liver TC and LDL, whereas LLA increased plasma HDL and markedly improved TC:HDL ratio. The HF-induced hepatic fat accumulation was attenuated by all treatments, of which VCO was the most effective. Control mice administered with LLA demonstrated lower liver TC and LDL, but higher plasma TC and HDL compared to controls. Lowest BW gain and food intake were found in mice treated with LLA. In conclusion, VCO, MCT, and LLA ameliorated hepatic histopathology caused by HF. VCO and MCT improved liver lipid profiles, whereas LLA has more beneficial effect on plasma lipids via a better TC:HDL ratio and showed promise for BW control.

Coadministration of olanzapine causes minor impacts on the diabetogenic outcomes induced by dexamethasone treatment in rats

AimsInvestigate whether the coadministration of olanzapine exacerbates the diabetogenic effects of dexamethasone, two agents used in the antiemetic cocktails indicated to mitigate the adverse effects of chemotherapy. Main methodsAdult Wistar rats (both sexes) were treated daily with dexamethasone (1 mg/kg, body mass (b.m.), intraperitoneal (i.p.)) with or without olanzapine (10 mg/kg, b.m., orogastric (o.g.)) for 5 consecutive days. During and at the end of the treatment, we evaluated biometric data and parameters involving glucose and lipid metabolism. Key findingsDexamethasone treatment resulted in glucose and lipid intolerance, higher plasma insulin and triacylglycerol levels, higher content of hepatic glycogen and fat, and higher islet mass in both sexes. These changes were not exacerbated by concomitant treatment with olanzapine. However, coadministration of olanzapine worsened the weight loss and plasma total cholesterol in males, while in females resulted in lethargy, higher plasma total cholesterol, and higher hepatic triacylglycerol release. SignificanceCoadministration of olanzapine does not exacerbate any diabetogenic dexamethasone effect on glucose metabolism and exerts a minor impact on the lipid homeostasis of rats. Our data favor the addition of olanzapine in the antiemetic cocktail considering the low incidence of metabolic adverse effects for the period and dosage analyzed in male and female rats.

Elevated adipose differentiation-related protein level in ovariectomized mice correlates with tissue-specific regulation of estrogen.

Redistribution of adipose tissue in the abdomen during the menopausal transition is attributable mostly to estrogen drop with aging. Adipose differentiation-related protein (ADRP), a major component of lipid droplets, is closely related to the onset of lipid accumulation. We hypothesized that estrogen exerted its tissue-specific effect in reducing abdominal fat accumulation by regulation of ADRP. Twenty-four female C57/BL6 mice aged 8 weeks were randomly divided into 3 groups: sham operation (Sham), bilateral ovariectomy (OVX), and OVX plus 17β-estradiol (OVX + E2). After being fed 8 weeks of a high-fat diet, plasma lipid profiles including total cholesterol (TC), total triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels, body weight gain, visceral, and subcutaneous adipose tissue, adipocyte size, and ADRP expression were measured. In comparison to sham-operated mice, OVX mice presented a weight gain with higher plasma TC, TG, LDL-C levels, and lower HDL-C levels. E2 supplement ameliorated the increase in weight and lipid profiles. Elevated ADRP expression was observed in visceral adipose tissue of OVX mice, whereas treatment of estrogen suppressed the ADPR expression and reversed the fat accumulation in the abdomen. However, no significant difference of ADRP expression in subcutaneous adipose tissue was detected between sham, OVX, and OVX + E2 mice. Our findings suggested that enhanced ADRP expression in ovariectomized mice correlates with the tissue-specific regulation of estrogen, which may provide useful clues for further exploring the regulatory mechanism and corresponding anti-abdominal obesity treatment in postmenopausal women.

151-LB: Impact of Concurrent Use of Selective Serotonin Reuptake Inhibitors and Second-Generation Antipsychotic Medications on Cardiometabolic Health in Children

Around 20% of Canadian children are diagnosed with a mental health disorder. Selective serotonin reuptake inhibitors (SSRIs) and second-generation antipsychotics (SGAs) are common treatments. Treatment with SSRIs or SGAs is associated with increased cardiometabolic complications, and risk for type 2 diabetes in children. Little is known about the metabolic effects of concurrent use of SSRIs with SGAs. Our aim was to determine if the combination of SSRI and SGA treatment was associated with cardiometabolic complications in children. Cross-sectional data were collected from children with mental health disorders (aged 5-18 years), recruited from Child and Adolescent Psychiatry at BC Children’s Hospital. Children were classified as naïve (n=242), SSRI-treated (n=123), SGA-treated (n=112), or SSRI+SGA treated (n=98). Anthropometric data and a fasting blood sample were collected. Relationships between treatment groups and cardiometabolic risk factors were determined by adjusted linear and logistic regression models. SSRI+SGA-treated children had higher waist circumference z-scores (0.91 ± 0.89 vs. 0.48 ± 0.95; P<0.05) and a greater odds of waist circumference ≥90th percentile (OR=2.63, 95% CI: 1.34, 5.18; P<0.05) compared to SSRI-treated children. SSRI+SGA-treated children had higher plasma total cholesterol (4.63 ± 0.93 vs. 4.34 ± 0.84 mmol/L; P<0.05, adjusted by age, sex, and BMI z-scores) and a greater odds of plasma total cholesterol ≥5.18 mmol/L (OR=2.36, 95% CI: 1.05, 5.30; P<0.05, adjusted by age, sex, and BMI z-scores) than SGA-treated children. No differences in plasma fasting glucose, insulin, or insulin resistance (HOMA-IR) were observed between the treatment groups. Concurrent SSRI+SGA treatment is associated with elevated waist circumference and plasma total cholesterol in children. Our findings suggest greater cardiometabolic complications in children concurrently treated with SSRIs and SGAs. Disclosure R. Thandi: None. A. M. Wiedeman: None. A. M. Devlin: None. C. Panagiotopoulos: Advisory Panel; Self; Dexcom, Inc., Speaker’s Bureau; Self; Eli Lilly and Company. Funding BC Mental Health and Substance Use Services

Differential effects of maternal diets on birth outcomes and metabolic parameters in rats after ethanol consumption during pregnancy.

Maternal nutrition status plays an important role in the development of fetal alcohol spectrum disorders (FASD), but its direct evidence is lacking. This study compared a standard chow with a semi-purified energy-dense (E-dense) diet on birth and metabolic outcomes in rats after ethanol (EtOH) consumption during pregnancy. Pregnant Sprague-Dawley rats were randomised into four groups: chow (n 6), chow+EtOH (20 %, v/v) (n 7), E-dense (n 6) and E-dense+EtOH (n 8). Birth outcomes including litter size, body and organ weights were collected. Metabolic parameters were measured in dams and pups at postnatal day (PD) 7. Maternal EtOH consumption decreased body weights (P < 0·0001) and litter sizes (P < 0·05) in chow-fed dams. At PD7, pups born to dams fed the E-dense diet had higher body (P < 0·002) and liver weights (P < 0·0001). These pups also had higher plasma total cholesterol (P < 0·0001), TAG (P < 0·003) and alanine aminotransferase (P < 0·03) compared with those from chow-fed dams. Dams fed the E-dense diet had higher plasma total (P < 0·0001) and HDL-cholesterol (P < 0·0001) and lower glucose (P < 0·0001). EtOH increased total cholesterol (P < 0·03) and glucose (P < 0·05) only in dams fed the E-dense diet. Maternal exposure to the E-dense diet attenuated prenatal EtOH-induced weight loss and produced different metabolic outcomes in both dams and pups. While the long-lasting effects of these outcomes are unknown, this study highlights the importance of maternal diet quality for maternal health and infant growth and suggests that maternal nutrition intervention may be a potential target for alleviating FASD.

Dyslipidemia and Associated Risk Factors among Nigerians with Hypertension

Background: Abnormalities in serum lipids and lipoprotein levels with essential hypertension are vital independent causal factors for atherosclerotic cardiovascular disease (ASCVD). The coexistence of these factors has a synergistic effect in heightening the risk of cardiovascular events. The aim of the study was to evaluate the pattern of dyslipidemia among hypertensives and to determine some of its correlations in patients attending a tertiary hospital in South South Nigeria. Methods: This was a cross-sectional study conducted on 544 eligible hypertensive patients attending the Cardiology Clinic, University of Uyo Teaching Hospital (UUTH), Uyo, Nigeria, over a period of 6 months. Fasting lipids, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were evaluated. Results: Overall, 60.0% of the hypertensive patients had dyslipidemia, with 43.4.0% having high TC, 30.3% high LDL-C, 20.8% elevated TG, and 12.9% low HDL-C, respectively. There was a significant relationship between gender and lipoproteins, with women having significantly higher lipoproteins (TC, HDL-C, LDL-C, and non-HDL-C) than men. Women also had more measures of obesity with a higher body mass index and waist circumference. TC and non-HDL had a significant association with both systolic and diastolic blood pressure (BP). Altogether, 43.4% of the hypertensives had poorly controlled BP and significantly higher atherogenic lipoproteins (TC, LDL-C, and non-HDL-C). Conclusion: This study has demonstrated the relatively high prevalence of dyslipidemia among hypertensive patient in this population. High plasma TC is the most dominant pattern of dyslipidemia. Hypertensive patients with poorly controlled BP have worse atherogenic lipoprotein values and are more likely predisposed to ASCVD.

Effects of vitamin D3 supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial

Alzheimer’s disease (AD) is the leading cause of dementia and loss of autonomy and independency in the elderly.1 Currently, no effective pharmacological interventions change the onset or progression of AD.2...

Evaluation of the relationship between plasma lipids and abdominal aortic aneurysm: A Mendelian randomization study.

Studies have reported that higher circulating levels of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and lower of high-density lipoprotein (HDL) cholesterol may be associated with increased risk of abdominal aortic aneurysm (AAA). Whether dyslipidemia causes AAA is still unclear and is potentially testable using a Mendelian randomization (MR) approach. We investigated the associations between blood lipids and AAA using two-sample MR analysis with SNP-lipids association estimates from a published genome-wide association study of blood lipids (n = 188,577) and SNP-AAA association estimates from European Americans (EAs) of the Atherosclerosis Risk in Communities (ARIC) study (n = 8,793). We used inverse variance weighted (IVW) MR as the primary method and MR-Egger regression and weighted median MR estimation as sensitivity analyses. Over a median of 22.7 years of follow-up, 338 of 8,793 ARIC participants experienced incident clinical AAA. Using the IVW method, we observed positive associations of plasma LDL cholesterol and TC with the risk of AAA (odds ratio (OR) = 1.55, P = 0.02 for LDL cholesterol and OR = 1.61, P = 0.01 for TC per 1 standard deviation of lipid increment). Using the MR-Egger regression and weighted median methods, we were able to validate the association of AAA risk with TC, although the associations were less consistent for LDL cholesterol due to wider confidence intervals. Triglycerides and HDL cholesterol were not associated with AAA in any of the MR methods. Assuming instrumental variable assumptions are satisfied, our finding suggests that higher plasma TC and LDL cholesterol are causally associated with the increased risk of AAA in EAs.

Abstract P199: Higher Circulating Triglycerides are Independently Associated With Greater Short-term Blood Pressure Variability in Middle-aged/older Adults With Obesity

Elevated short-term (24 hour) blood pressure variability (BPV) is associated with subclinical target organ damage and cardiovascular disease (CVD) among middle-aged/older (MA/O) adults with hypertension and obesity. Circulating total cholesterol (TC), low-density cholesterol (LDL-C) and triglycerides (TGs) increase with human obesity and are independent risk factors for CVD. In addition, BPV is increased in mouse models of hyperlipidemia and is normalized with statins. However, whether higher circulating lipoproteins independently contribute to greater short-term BPV among adults with obesity remains unclear. We hypothesized that higher LDL-C, TGs and lower high-density lipoprotein (HDL-C) would be associated with greater short-term BPV among individuals with obesity. Fasting plasma lipids and 24 hour ambulatory BP monitoring were assessed in fifty-six MA/O adults with obesity defined as body mass index (BMI) ≥ 30 kg/m 2 (56% F; age 54±7 yrs; BMI, 38.2±5.6 kg/m 2 ) and at least one other CVD risk factor. There was a significant relation between 24 hour systolic BPV and TC (r=0.30, P=0.03), TGs (r=0.34, P=0.01) and LDL-C (r=0.25, P=0.059), but not HDL-C (r=-0.07, P=0.61). Interestingly, these findings remained significant after adjusting for age, sex, BMI and 24 hour systolic BP (TC: r=0.34, P=0.01; TGs: r=0.39, P&lt;0.01; LDL-C: r=0.31, P=0.03) but HDL-C remained non-significant (r=-0.16, P=0.27). In contrast, other cardiometabolic risk factors such as fasting glucose, insulin, c-reactive protein concentrations, carotid-femoral pulse wave velocity and HOMA-IR were not associated with 24 hour systolic BPV. In a multiple linear regression model that included age, sex, BMI, 24 hour systolic BP, TGs and LDL-C, only fasting TGs (β=0.02 ± 0.01, P=0.02) were a significant correlate of 24 hour systolic BPV (Model R 2 =0.24, P=0.03). Results were the same if TC was substituted for LDL-C in the model. In conclusion, higher plasma TC, LDL-C and TGs are associated with greater 24 hour BPV among MA/O adults with obesity with only TGs being independently associated with BPV. These data suggest that greater variability in BP among MA/O adults with obesity is mediated in part through circulating TGs suggesting that TGs may be a therapeutic target to modify short-term BPV.

Abstract 149: Analysis of Radiotherapy Induced Vascular Lesions Reveals Potential Therapies Against Innate Inflammation in an ApoE Knockout Mouse Model

Clinical studies show an increase risk for cardiovascular disease (CVD) at the site of irradiation years after exposure. Radiotherapy together with other cancer therapies contributes to a growing population of cancer survivors in risk of developing radiotherapy induced vascular disease. However, traditional treatments for CVD such as thrombolytic inhibitors and lipid lowering drugs (statins) seem to have no effect on radiation induced vascular disease in mouse models. We have previously demonstrated a sustained chronic inflammation by NF-kB activation in irradiated human arteries. To further investigate radiation induced vascular disease and potential therapies against innate inflammation, we established a mouse model of local irradiation in an atherosclerotic prone ApoE-/- background. ApoE-/- mice fed chow diet were exposed to a single dose of 0 Gy (sham/controls) or 14 Gy at the upper chest and neck area and harvested 10 weeks later. Plasma, thoracic aorta, aortic arch, heart were retrieved and taken for plasma, blood count, en face, mRNA, immunohistochemistry and immunofluorescence analysis. Irradiated mice presented higher total plasma cholesterol levels than controls. En face analysis of aortic arches showed a decreased percentage of lesion size in irradiated arteries compared to controls. However, an increase of MHC class II (IA-b) staining in irradiated aortic roots suggested an induction of inflammation in the context of radiotherapy. These data were supported by the quantification of monocyte chemotactic protein 1 mRNA expression in the thoracic aorta showing a significant increase in irradiated animals compared to unirradiated (p≤0,001). The current data demonstrated that radiotherapy induces a macrophage-rich and inflamed plaque that may explain the increased risk of developing severe clinical events i.e. myocardial infarction or stroke. Further analyses of this partial irradiation mouse model are on-going to assess the potential therapeutic targets involved in innate immunity and NF-kB activation. Results of currently performed therapeutic experiments will be further presented.

Effect of polymorphisms in interleukin-18 gene on the susceptibility to coronary artery disease in a Chinese population.

Coronary artery disease (CAD) has a high mortality rate in several countries. Interleukin (IL)-18 has been previously correlated with atherosclerotic plaque rupture. In this case-control study, the relationship between -607A/C and -372C/G promoter polymorphisms in IL-18 and risk of CAD development was investigated. A total of 326 CAD patients were consecutively recruited from the First Hospital of Yulin between March 2013 and May 2015. The IL-18 -607A/C and -372C/G polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Patients with CAD had a higher body mass index, a history of hypertension or diabetes (all P < 0.001), cigarette smoking habit (P = 0.002); as well as higher plasma total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels (all P < 0.001) and lower high-density lipoprotein cholesterol (P < 0.001) levels compared to the control subjects. Unconditional logistic regression analysis revealed significant correlation between the CC genotype of IL-18 -607A/C and CAD development, compared to the AA genotype [adjusted odds ratio (OR) = 2.42; 95% confidence interval (CI) = 1.52-3.89; P < 0.001]. The recessive model showed a significant association between the CC genotype of IL-18 -607A/C and an increased risk of CAD, compared to the AA+AC genotype (OR = 2.51, 95%CI = 1.65-3.85). However, IL-18 -372C/G did not contribute to the risk of glioma development in the co-dominant, dominant, and recessive models. Therefore, the IL-18 -607C/A polymorphism was significantly correlated with the risk of CAD development.

Vitamin D Deficiency in Community-Dwelling Elderly Is Not Associated with Age-Related Macular Degeneration1–3

Background: Elderly persons are at elevated risk of vitamin D deficiency, which is involved in various health problems. However, its relation with age-related macular degeneration (AMD) is debated.Objectives: We investigated factors associated with plasma 25-hydroxyvitamin D [25(OH)D] deficiency and the associations between plasma 25(OH)D concentrations and AMD in elderly subjects.Methods: Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes (ALIENOR) is a population-based study on eye diseases performed in elderly residents of Bordeaux, France. Plasma 25(OH)D concentrations were assessed from blood samples and categorized as <25 nmol/L (deficiency), 25–49 nmol/L (insufficiency), or ≥50 nmol/L (sufficiency). AMD was classified as: no AMD, early AMD, and late AMD. Associations between baseline characteristics and plasma 25(OH)D status were examined with multinomial logistic regression analysis. Associations between AMD and plasma 25(OH)D status were estimated using generalized estimating equation logistic regressions.Results: Six hundred ninety-seven subjects with complete data were included. The prevalence of plasma 25(OH)D deficiency and insufficiency were 27.3% and 55.9%, respectively. In multivariate analysis, 25(OH)D deficiency was significantly associated with older age (P = 0.0007), females (P = 0.0007), absence of physical activity (P = 0.01), absence of vitamin D supplementation (P < 0.0001), higher plasma total cholesterol (P = 0.007), use of fibrates (P < 0.0001), lower alcohol consumption (P = 0.02), and season of blood sampling (P < 0.0001). After adjustment for these covariates and dietary omega-3 polyunsaturated fatty acid intake, smoking, and body mass index, no significant associations were found between early AMD and 25(OH)D insufficiency or deficiency (OR: 0.71, P = 0.12; OR: 0.73, P = 0.23, respectively) or with late AMD (OR: 1.04, P = 0.93; OR: 0.74, P = 0.59, respectively).Conclusion: These findings underline the very high prevalence of plasma 25(OH)D deficiency in this elderly population but do not support a specific role for vitamin D in AMD.

The effect of Ramadan fasting on non-alcoholic fatty liver disease (NAFLD) patients

Introduction: The aim of this study was to compare biochemical tests, body composition and anthropometric parameters in Nonalcoholic Fatty Liver Disease (NAFLD) patients before and after Ramadan fasting. Methods: fifty NAFLD patients including 33 males and 17 females aged 18-65 year, were recruited. Subjects attended after diagnosis based on ultrasound imaging, with at least 10 hour fasting, before and after Ramadan who were been fasting for at least 10 days. A fasting blood sample was obtained, blood pressure was measured and body mass index(BMI) and fat mass (FM) and fat free mass (FFM) were calculated. Lipid profile, fasting blood sugar (FBS),insulin, ALT and AST enzymes were analyzed on all blood samples. Result: There was a significant increase in HDL-c in females and higher total plasma cholesterol, triglyceride (TG) and FBS in both gender while lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and ALT decreasing after Ramadan (P 0.05, t test). Conclusion: This study shows significant effects on NAFLD patient parameters during Ramadan fasting such as decreasing in insulin, ALT enzyme, SBP and DBP and increasing in HDL-c after an average of 27 d fasting, Result from this study suggested that Ramadan fasting may be useful to improve NAFLD, so further studies are needed in this area.

Abstract 207: Interesterified Fat Rich in Stearic Acid Increases Liver Neutrophil and M1 Macrophage Infiltration and Induces Nonalcoholic Steatohepatitis

Introduction: interesterified fats, rich in saturated fatty acid, have been used by food industry to replace trans. Palmitic acid is the most common dietary fat with known deleterious effects. On the hand stearic acid which is consumed in a low amount, has neutral effect on plasma lipids. Unlike vegetable oils, interesterified fats contain palmitic or stearic acid in the sn-2 position and the positional compositon of triglicerides may regulate its metabolic fate. Thus, the aim of this study was to evaluate the effect on the liver metabolism of the interesterified fats rich in stearic or palmitic fatty acids. Methods: Weaning LDLr-KO male mice were randomly distributed into five groups fed a high fat diet (40% of energy as fat) containing polyunsaturated (PUFA), palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR) or stearic interesterified (STEAR INTER) during 16 weeks. Total plasma cholesterol and triglyceride concentrations, liver total cholesterol, triglycerides and weight, neutrophil (neutr/area) and classically activated/inflammatory M1(CD11b) infiltrated macrophage were determined. Histological markers of NAFLD activity were assessed. Results: There were no differences in dietary intakes among all groups. The interesterification process did not alter plasma lipids concentrations (mg/dL±SD): PALM vs PALM INTER (499.2 ± 81.7 vs 526.8 ± 92.6) and STEAR vs STEAR INTER (342.6 ± 89.9 vs 363.9 ± 90.0). However, PALM and PALM INTER presented higher total plasma cholesterol, and STEAR and STEAR INTER showed total cholesterol concentrations similar to POLI (320.7±47.4). Liver weight, cholesterol and TG contents did not differ among the groups. POLI and STEARIC groups do not elicit NASH (score &lt;3), PALM and PALM INTER presented intermediate stage (score ≤4) between STEARIC/POLI and STEARIC INTER. Nevertheless, STEAR INTER developed NASH (score ≥5), and induce higher neutrophil infiltration (5.53 ±4.1) as compared to all other groups. The M1 macrophage classically activated infiltration was also higher in STEAR INTER group than in all groups as demonstrated by imunofluorescence. Conclusion: STEAR INTER brings on NASH lesion, increased neutrophil and M1 macrophage classically activated/inflammatory infiltration in the liver.

Plasma oxidized low density lipoprotein cholesterol correlates inversely with testosterone in young adult male smokers.

IntroductionThere are indications that oxidized low density lipoprotein cholesterol (Ox-LDLC) may play an important role in cardiovascular disease (CVD) events. In most developing countries, the interplay between the different lipid fractions and cigarette smoking has not been studied. This study assessed the effect of cigarette smoking on the alterations in plasma lipid fractions and their associations with the gonadal hormone, testosterone (T).MethodsOne hundred and sixty male participants, consisting of eighty smokers and eighty apparently healthy non-smokers were recruited. Anthropometric indices and biochemical parameters were determined using standard procedures.ResultsSignificant increases were obtained in plasma total cholesterol (TC), triglyceride (TG), oxidized low density lipoprotein (Ox-LDLC) and Ox-LDLC/TT ratio (p<0.001) in smokers compared with the non-smokers. Plasma high density cholesterol (HDLC) (p<0.001) was significantly reduced in smokers compared with the non-smokers. The plasma mean T result was not significantly different from the non-smokers, but inversely correlated with Ox-LDLC and significantly correlated with the lipids and lipoproteins. Significantly high plasma TC, TG and LDLC (p<0.001) and low HDLC (p<0.001) were also obtained in smokers when co-founding factors such as duration and number of cigarette smoked per day were applied.ConclusionThis study showed an inverse correlation between Ox-LDLC and testosterone as well as strong association between the number of tobacco and cigarettes usage per day. These changes in part, could be major causes of premature CVD and decreased fertility in young adults.

Effect of prickly pear cactus (Opuntina ficus-indica) intake on blood lipids, platelet aggregation, antioxidant and liver parameters in volunteer diving woman

We investigated dietary effects of prickly pear cactus (Opuntina ficus-indica ) on plasma lipids, platelet aggregation (PA), hemolysis, plasma TBARS and liver enzymes. Twenty eight volunteer diving women in Jeju island had daily 20 g cactus tea containing 27% prickly pear cactus (PPC) powder for 4 weeks, and data for the study subjects were analyzed, on the basis of diagnostic criteria for blood pressure (BP)(≥ 140/90 mmHg), plasma cholesterol (≥ 200 mg/dL) and triglyceride (≥ 150 mg/dL). The subjects with higher BP had higher plasma total cholesterol (TC) and triglyceride (TG) concentrations than those with normal BP. Those with higher TC also had higher TG. Subjects with normal BP or normal TC had higher initial slope of PA than their higher counterpart in BP and TC. PPC intake decreased plasma TG in those with higher BP. PPC intake significantly decreased the elevated initial slope in groups with normal BP, TC, and TG. Hemolysis after PPC intake decreased significantly in all the subjects and plasma TBARS decreased in the sub jects with higher plasma TC and higher TG. Glutamic-oxaloacetic transaminase (GOT) significantly increased and to tal bilirubin significantly decreased in all the subjects after PPC intake. The present study with diving women showed that beneficial effects of short term intake of prickly pear cactus might differ depending on the subject conditions in term of blood pressure, and plasma lipids. However, long term usage of prickly pear cactus may provide preventive effects of cardiovascular diseases to all the population, presumably by hypolipidemic, antithrombotic, and antioxidant actions of its bioactive flavonoids and soluble fiber. (Korean J Nutr 2012; 45(5): 462 ~ 469)

ApoB100/LDLR-/- Hypercholesterolaemic Mice as a Model for Mild Cognitive Impairment and Neuronal Damage

Recent clinical findings support the notion that the progressive deterioration of cholesterol homeostasis is a central player in Alzheimer's disease (AD). Epidemiological studies suggest that high midlife plasma total cholesterol levels are associated with an increased risk of AD. This paper reports the plasma cholesterol concentrations, cognitive performance, locomotor activity and neuropathological signs in a murine model (transgenic mice expressing apoB100 but knockout for the LDL receptor [LDLR]) of human familial hypercholesterolaemia (FH). From birth, these animals have markedly elevated LDL-cholesterol and apolipoprotein B100 (apoB100) levels. These transgenic mice were confirmed to have higher plasma cholesterol concentrations than wild-type mice, an effect potentiated by aging. Further, 3-month-old transgenic mice showed cholesterol (total and fractions) concentrations considerably higher than those of 18-month-old wild-type mice. The hypercholesterolaemia of the transgenic mice was associated with a clear locomotor deficit (as determined by rotarod, grip strength and open field testing) and impairment of the episodic-like memory (determined by the integrated memory test). This decline in locomotor activity and cognitive status was associated with neuritic dystrophy and/or the disorganization of the neuronal microtubule network, plus an increase in astrogliosis and lipid peroxidation in the brain regions associated with AD, such as the motor and lateral entorhinal cortex, the amygdaloid basal nucleus, and the hippocampus. Aortic atherosclerotic lesions were positively correlated with age, although potentiated by the transgenic genotype, while cerebral β-amyloidosis was positively correlated with genetic background rather than with age. These findings confirm hypercholesterolaemia as a key biomarker for monitoring mild cognitive impairment, and shows these transgenic mice can be used as a model for cognitive and psycho-motor decline.

Health evaluation of high nutritional value meals for school children

This study was done to evaluate the safety and health value of five meals formulated for school children. The constituents used for formulation of these meals were a group of vegetables and legumes such as spinach, cauliflower, carrot, tomato, germinated broad beans, soybean, chickpea, peanut, sesame in addition to whey protein and wheat germ. The evaluation was done through a feeding experiment using rats. Growth parameters such as body weight, and food efficiency ratio proved the high nutritional value of these meals. Assessment of organs function showed that no change in the activities of AST, ALT and γ Glutamyl Transpeptidase occurred indicating normal liver function. The parameters of the kidney function namely the concentration of plasma uric acid, urea and creatinine were all having normal values indicating normal kidney function. The oxidation state of the body is in the positive state with normal activity of each of the antioxidant enzymes superoxide dismutase and glutathione peroxidase together with low value of plasma malondialdhyde. Rats fed on each of these meals had higher plasma total cholesterol, LDL, HDL and normal triglycerides. The significance of these findings was discussed the conclusion is that these meals are of high nutritional value, safe with regard to the liver and kidney functions, promote antioxidant defense against free radicals and with no serious hazards regarding lipid disorders. This makes such meals worth to be consumed by children alternate to fast food that can exert health problems.

Morphology and structure of lipoproteins revealed by an optimized negative-staining protocol of electron microscopy

Plasma lipoprotein levels are predictors of risk for coronary artery disease. Lipoprotein structure-function relationships provide important clues that help identify the role of lipoproteins in cardiovascular disease. The compositional and conformational heterogeneity of lipoproteins are major barriers to the identification of their structures, as discovered using traditional approaches. Although electron microscopy (EM) is an alternative approach, conventional negative staining (NS) produces rouleau artifacts. In a previous study of apolipoprotein (apo)E4-containing reconstituted HDL (rHDL) particles, we optimized the NS method in a way that eliminated rouleaux. Here we report that phosphotungstic acid at high buffer salt concentrations plays a key role in rouleau formation. We also validate our protocol for analyzing the major plasma lipoprotein classes HDL, LDL, IDL, and VLDL, as well as homogeneously prepared apoA-I-containing rHDL. High-contrast EM images revealed morphology and detailed structures of lipoproteins, especially apoA-I-containing rHDL, that are amenable to three-dimensional reconstruction by single-particle analysis and electron tomography.