Management of Hypercholesterolemia Through Dietary ß-glucans–Insights From a Zebrafish Model

Consumption of lipid-rich foods can increase the blood cholesterol content. β-glucans have hypocholesterolemic effect. However, subtle changes in their molecular branching can influence bioactivity. Therefore, a comparative investigation of the cholesterol-lowering potential of two β-glucans with different branching patterns and a cholesterol-lowering drug, namely simvastatin was undertaken employing the zebrafish (Danio rerio) model of diet-induced hypercholesterolemia. Fish were allocated to 5 dietary treatments; a control group, a high cholesterol group, two β-glucan groups, and a simvastatin group. We investigated plasma total cholesterol, LDL and HDL cholesterol levels, histological changes in the tissues, and explored intestinal transcriptomic changes induced by the experimental diets. Dietary cholesterol likely caused the suppression of endogenous cholesterol biosynthesis, induced dysfunction of endoplasmic reticulum and mitochondria, and altered the histomorphology of the intestine. The two β-glucans and simvastatin significantly abated the rise in plasma cholesterol levels and restored the expression of specific genes to alleviate the endoplasmic reticulum-related effects induced by the dietary cholesterol. Furthermore, the distinct patterns of transcriptomic changes in the intestine elicited by the oat and microalga β-glucans impacted processes such as fatty acid metabolism, protein catabolic processes, and nuclear division. Oat and microalgal β-glucans also altered the pattern of lipid deposition in the liver. Our study provides insights into the effectiveness of different β-glucans to alleviate dysfunctions in lipid metabolism caused by dietary cholesterol.

(Pro)renin Receptor Inhibition Reduces Plasma Cholesterol and Triglycerides but Does Not Attenuate Atherosclerosis in Atherosclerotic Mice

Objective: Elevated plasma cholesterol concentrations contributes to ischemic cardiovascular diseases. Recently, we showed that inhibiting hepatic (pro)renin receptor [(P)RR] attenuated diet-induced hypercholesterolemia and hypertriglyceridemia in low-density lipoprotein receptor (LDLR) deficient mice. The purpose of this study was to determine whether inhibiting hepatic (P)RR could attenuate atherosclerosis.Approach and Results: Eight-week-old male LDLR−/− mice were injected with either saline or N-acetylgalactosamine-modified antisense oligonucleotides (G-ASOs) primarily targeting hepatic (P)RR and were fed a western-type diet (WTD) for 16 weeks. (P)RR G-ASOs markedly reduced plasma cholesterol concentrations from 2,211 ± 146 to 1,128 ± 121 mg/dL. Fast protein liquid chromatography (FPLC) analyses revealed that cholesterol in very low-density lipoprotein (VLDL) and intermediate density lipoprotein (IDL)/LDL fraction were potently reduced by (P)RR G-ASOs. Moreover, (P)RR G-ASOs reduced plasma triglyceride concentrations by more than 80%. Strikingly, despite marked reduction in plasma lipid concentrations, atherosclerosis was not reduced but rather increased in these mice. Further testing in ApoE−/− mice confirmed that (P)RR G-ASOs reduced plasma lipid concentrations but not atherosclerosis. Transcriptomic analysis of the aortas revealed that (P)RR G-ASOs induced the expression of the genes involved in immune responses and inflammation. Further investigation revealed that (P)RR G-ASOs also inhibited (P)RR in macrophages and in enhanced inflammatory responses to exogenous stimuli. Moreover, deleting the (P)RR in macrophages resulted in accelerated atherosclerosis in WTD fed ApoE−/− mice.Conclusion: (P)RR G-ASOs reduced the plasma lipids in atherosclerotic mice due to hepatic (P)RR deficiency. However, augmented pro-inflammatory responses in macrophages due to (P)RR downregulation counteracted the beneficial effects of lowered plasma lipid concentrations on atherosclerosis. Our study demonstrated that hepatic (P)RR and macrophage (P)RR played a counteracting role in atherosclerosis.

An Overview on Hyperlipidemia

Introduction: Hyperlipidemia is a medical condition indicated by an increase in one or more plasma lipids, such as triglycerides, cholesterol, cholesterol esters, phospholipids, and/or plasma lipoproteins, such as very low-density lipoprotein and low-density lipoprotein, as well as decreased levels of high-density lipoprotein. This increase in plasma lipids is one of the most important risk factors for cardiovascular disease. In the meanwhile, statins and fibrates remain the most common anti-hyperlipidemic drugs for treating high plasma cholesterol and triglycerides. Conclusion: Hence this review focused to study of hyperlipidemia. This review is useful to research work in hyperlididemia.

The protective effect of the aqueous extract of parsley (Petroselinum sativum ) seeds on experimentally – induced oxidative stress in rats

In this study, the potential protective effect of aqueous extract of parsley (Petroselinum sativum) seeds against hydrogen peroxide (H2O2) – induced oxidative stress in male rats was assessed. Three groups of male albino rats were randomly divided (n=7) and were handled for twenty-eight days as follows: rats in group I served as control; animals in group || were provided with drinking water containing 0.5% H2O2 and those in group III received orally 8 mg/100 gm B.W. of aqueous extract of parsley seeds plus 0.5% H2O2 in drinking water. After four weeks experimental period, a significant increase in lipid peroxidation products (MDA), and decrease in glutathione (GSH) concentrations were observed in plasma, kidney, liver and heart tissues of H2O2 treated animals as compared with the control group. These biomarkers (GSH and MDA) are interrelated and indicate the occurrence of oxidative stress. Plasma total cholesterol (TC) concentration was significantly increased in H2O2 treated rats. By administration of aqueous extract of parsley along with H2O2, plasma and tissue GSH levels were significantly increased while the elevation in MDA level was diminished in plasma and different tissues examined. A decrease in plasma cholesterol concentration was recorded in H2O2 and parsley treated group as compared with the control one and H2O2 treated groups. These results indicate that aqueous extract of parsley have hypocholesterolemic and antioxidant effect.

Intestinal, liver and lipid disorders in genetically obese rats are more efficiently reduced by dietary milk thistle seeds than their oil

We hypothesized that milk thistle seed or seed oil dietary supplementation reduces intestinal, liver and lipid disorders specific to genetic obesity, and the seeds can be more efficient in doing so. Lean and obese male Zucker rats were allocated to 4 groups: the lean (LC) and obese control (OC) groups fed a standard diet and the other 2 obese groups fed a diet supplemented with milk thistle seed oil (O + MTO) or milk thistle seeds (O + MTS). After 5 weeks of feeding, the cecal SCFA pool was slightly and significantly lower in OC and O + MTO compared with LC and O + MTS. The liver fat content was greater in OC, O + MTO and O + MTS compared with LC; however, it was significantly lower in O + MTS than in OC and O + MTO. The plasma cholesterol was greater in OC compared with LC, O + MTO and O + MTS; however, it was significantly greater in O + MTO and O + MTS compared with LC. The plasma bilirubin was detected in OC and O + MTO, whereas it was not present in LC and O + MTS. Milk thistle seeds can improve fermentation events in the distal intestine and reduce other disorders specific to genetically obese rats, and the seed PUFAs are responsible for that to a lesser extent.

Pleiotropic Effects of Atorvastatin Result in a Downregulation of the Carboxypeptidase U System (CPU, TAFIa, CPB2) in a Mouse Model of Advanced Atherosclerosis

Statins (hydroxymethyl-glutaryl-CoA-reductase inhibitors) lower procarboxypeptidase U (proCPU, TAFI, proCPB2). However, it is challenging to prove whether this is a lipid or non-lipid-related pleiotropic effect, since statin treatment decreases cholesterol levels in humans. In apolipoprotein E-deficient mice with a heterozygous mutation in the fibrillin-1 gene (ApoE−/−Fbn1C1039G+/−), a model of advanced atherosclerosis, statins do not lower cholesterol. Consequently, studying cholesterol-independent effects of statins can be achieved more straightforwardly in these mice. Female ApoE −/−Fbn1C1039G+/− mice were fed a Western diet (WD). At week 10 of WD, mice were divided into a WD group (receiving WD only) and a WD + atorvastatin group (receiving 10 mg/kg/day atorvastatin +WD) group. After 15 weeks, blood was collected from the retro-orbital plexus, and the mice were sacrificed. Total plasma cholesterol and C-reactive protein (CRP) were measured with commercially available kits. Plasma proCPU levels were determined with an activity-based assay. Total plasma cholesterol levels were not significantly different between both groups, while proCPU levels were significantly lower in the WD + atorvastatin group. Interestingly proCPU levels correlated with CRP and circulating monocytes. In conclusion, our results confirm that atorvastatin downregulates proCPU levels in ApoE−/−Fbn1C1039G+/− mice on a WD, and evidence was provided that this downregulation is a pleiotropic effect of atorvastatin treatment.

A COMPARATIVE CLINICAL STUDY TO EVALUATE THE EFFECTIVENESS OF TRYUSHSANADHI GUGGULU AND NAVAKA GUGGULU IN DYSLIPIDEMIA

Dyslipidemia occurs when there is an elevation in the levels of plasma cholesterol, triglycerides, or a decreased level of HDL levels. It is one of the main causes that contribute to the event of atherosclerosis and a major cause of various lifestyle disorders. Dyslipidemia being the common issue faced by mankind, there is a necessity to combat it with the drugs mentioned in the classics. In this regard, an attempt has been made to critically review the action of two important drugs mentioned in the classical texts which help in managing Dyslipidemia. The pre- sent study was aimed to assess the clinical effectiveness of Tryushanadhi guggulu and Navaka guggulu in Dyslipidemia and to compare the effectiveness of both after therapy. This comparative clinical study was con- ducted with pre and post designs in 40 patients diagnosed with Dyslipidemia with 20 patients in each in two groups viz Group A and Group B treated with Tryushanadhi guggulu and Navaka guggulu respectively. The as- sessment was done before and after the treatment with Objective criteria. After a thorough assessment, it was found out that Group A (Tryushanadhi guggulu:20.87%) had better results compared to Group B (Navaka guggu- lu:10.37%). Keywords: Dyslipidemia, Tryushanadhi guggulu, Navaka guggulu, Medoroga

Identification of loci associated with pathological outcomes in Holstein cattle infected with Mycobacterium avium subsp. paratuberculosis using whole-genome sequence data

Bovine paratuberculosis (PTB), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic granulomatous enteritis that affects cattle worldwide. According to their severity and extension, PTB-associated histological lesions have been classified into the following groups; focal, multifocal, and diffuse. It is unknown whether these lesions represent sequential stages or divergent outcomes. In the current study, the associations between host genetic and pathology were explored by genotyping 813 Spanish Holstein cows with no visible lesions (N = 373) and with focal (N = 371), multifocal (N = 33), and diffuse (N = 33) lesions in gut tissues and regional lymph nodes. DNA from peripheral blood samples of these animals was genotyped with the bovine EuroG MD Bead Chip, and the corresponding genotypes were imputed to whole-genome sequencing (WGS) data using the 1000 Bull genomes reference population. A genome-wide association study (GWAS) was performed using the WGS data and the presence or absence of each type of histological lesion in a case–control approach. A total of 192 and 92 single nucleotide polymorphisms (SNPs) defining 13 and 9 distinct quantitative trait loci (QTLs) were highly-associated (P ≤ 5 × 10−7) with the multifocal (heritability = 0.075) and the diffuse (heritability = 0.189) lesions, respectively. No overlap was seen in the SNPs controlling these distinct pathological outcomes. The identified QTLs overlapped with some QTLs previously associated with PTB susceptibility, bovine tuberculosis susceptibility, clinical mastitis, somatic cell score, bovine respiratory disease susceptibility, tick resistance, IgG level, and length of productive life. Pathway analysis with candidate genes overlapping the identified QTLs revealed a significant enrichment of the keratinization pathway and cholesterol metabolism in the animals with multifocal and diffuse lesions, respectively. To test whether the enrichment of SNP variants in candidate genes involved in the cholesterol metabolism was associated with the diffuse lesions; the levels of total cholesterol were measured in plasma samples of cattle with focal, multifocal, or diffuse lesions or with no visible lesions. Our results showed reduced levels of plasma cholesterol in cattle with diffuse lesions. Taken together, our findings suggested that the variation in MAP-associated pathological outcomes might be, in part, genetically determined and indicative of distinct host responses.

333 Assessment of Spent Hemp Biomass as a Potential Feedstuff in Ruminant Diets

The 2018 Farm Bill removed hemp (Cannabis sativa) from the Controlled Substances Act, classifying it as an agricultural product. The process of cannabidiol extraction from hemp yields large quantities of spent hemp biomass (SHB) that may potentially be included in animal diets. However, the use of SHB in animal diets has not been approved by FDA yet since its effect on animal health, production and product quality is still unknown. Thus, a feeding study was carried out to investigate the effects of varying levels of SHB and a four-week withdrawal period on feed intake and liveweight gains of weaned lambs. A total of 35 weaned, male Polypay lambs kept in single pens were randomly assigned to five feeding treatments (n=7) and fed diets containing either no SHB (CON) or SHB at 10% (LH1) or 20% (HH1) for 4 weeks with 4 weeks withdrawal from SHB, or SHB at 10 (LH2) or 20% (HH2) for 8 weeks. The nutritive analysis of the SHB indicated a high-quality feed, with 20% (DM) crude protein and 27% NDF. Dry matter (DM) intake of lambs was negatively affected by 20% SHB during the first period. In the second period, DM intake was larger in lambs fed 10% SHB vs. CON, with the largest feed intake observed in HH1 lambs. In contrast, none of the performance data, including liveweight gains, were different across the groups and periods. Feeding 20% SHB decreased plasma cholesterol, NEFA, BHBA, Ca, and Cl and increased urea and Mg, while 10% SHB increased glucose, cholesterol, and NEFA. Our findings indicated that 10% SHB can be included in ruminant diets without causing any detrimental effect on performance with a possible positive effect on feed intake. The long-term feeding of 20% SHB strongly affects the metabolism.

Inflammatory markers and lipid profiles in obese children

Background Over 340 million children and adolescents aged 5-19 were overweight or obese in the year 2016. Individuals with obesity are at risk for metabolic disorders and lipid abnormalities. Adipose tissue is a major source of pro-inflammatory cytokines. Objective To evaluate possible correlations between inflammatory markers IL-6, TNFa, and hs-CRP with lipid profiles between obese and non obese children. Methods Eighty children, aged 13 to 15 years, were enrolled in this study (40 normoweight and 40 obese). All participants’s ( obese and normoweight children) total plasma cholesterol, HDL cholesterol, triglycerides, as well as circulating levels of inflammatory factors, such as TNF-α, IL-6, and high sensitivity-C-reactive protein (hs-CRP) level were measured. Results Obese children had significantly higher triglycerides (TG) and cholesterol, as well as lower HDL than normoweight subjects. Mean LDL levels were not significantly different between groups. The IL-6, TNFa, hs-CRP levels were significantly positively correlated with waist circumference. Analysis of the 4 blood lipid parameters and 3 inflammatory markers revealed significant positive correlations of triglycerides to TNFa and hs-CRP. In addition, HDL had significant negative correlations to both TNFa and hs-CRP. No correlations were found between IL-6 and the 4 lipid parameters, nor between TNFa or hs-CRP to LDL and cholesterol. Multivariate regression analysis revealed a significant association between weight-height ratio with hs-CRP (R2 0.118; 95%CI 1.65 to 191; P=0.046). Obesity is associated with adverse lipid and inflammations markers in children. Conclusion Obesity was associated with higher TG, cholesterol, TNF, and hs-CRP levels, as well as lower HDL.