Reduced Plasma Total Cholesterol Research Articles

A novel small-molecule PCSK9 inhibitor E28362 ameliorates hyperlipidemia and atherosclerosis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor precursor homologous domain A (EGF-A) of low-density lipoprotein receptor (LDLR) in the liver and triggers the degradation of LDLR via the lysosomal pathway, consequently leading to an elevation in plasma LDL-C levels. Inhibiting PCSK9 prolongs the lifespan of LDLR and maintains cholesterol homeostasis in the body. Thus, PCSK9 is an innovative pharmacological target for treating hypercholesterolemia and atherosclerosis. In this study, we discovered that E28362 was a novel small-molecule PCSK9 inhibitor by conducting a virtual screening of a library containing 40,000 compounds. E28362 (5, 10, 20 μM) dose-dependently increased the protein levels of LDLR in both total protein and the membrane fractionin both HepG2 and AML12 cells, and enhanced the uptake of DiI-LDL in AML12 cells. MTT assay showed that E28362 up to 80 μM had no obvious toxicity in HepG2, AML12, and HEK293a cells. The effects of E28362 on hyperlipidemia and atherosclerosis were evaluated in three different animal models. In high-fat diet-fed golden hamsters, administration of E28362 (6.7, 20, 60 mg·kg-1·d-1, i.g.) for 4 weeks significantly reduced plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and PCSK9 levels, and reduced liver TC and TG contents. In Western diet-fed ApoE-/- mice (20, 60 mg·kg-1·d-1, i.g.) and human PCSK9 D374Y overexpression mice (60 mg·kg-1·d-1, i.g.), administration of E28362 for 12 weeks significantly decreased plasma LDL-C levels and the area of atherosclerotic lesions in en face aortas and aortic roots. Moreover, E28362 significantly increased the protein expression level of LDLR in the liver. We revealed that E28362 selectively bound to PCSK9 in HepG2 and AML12 cells, blocked the interaction between LDLR and PCSK9, and induced the degradation of PCSK9 through the ubiquitin-proteasome pathway, which finally resulted in increased LDLR protein levels. In conclusion, E28362 can block the interaction between PCSK9 and LDLR, induce the degradation of PCSK9, increase LDLR protein levels, and alleviate hyperlipidemia and atherosclerosis in three distinct animal models, suggesting that E28362 is a promising lead compound for the treatment of hyperlipidemia and atherosclerosis.

A long-acting LEAP2 analog reduces hepatic steatosis and inflammation and causes marked weight loss in mice

ObjectiveThe number of individuals affected by metabolic dysfunction associated fatty liver disease [1] is on the rise, yet hormonal contributors to the condition remain incompletely described and only a single FDA-approved treatment is available. Some studies suggest that the hormones ghrelin and LEAP2, which act as agonist and antagonist/inverse agonist, respectively, for the G protein coupled receptor GHSR, may influence the development of MAFLD. For instance, ghrelin increases hepatic fat whereas synthetic GHSR antagonists do the opposite. Also, hepatic steatosis is less prominent in standard chow-fed ghrelin-KO mice but more prominent in 42% high-fat diet-fed female LEAP2-KO mice. MethodsHere, we sought to determine the therapeutic potential of a long-acting LEAP2 analog (LA-LEAP2) to treat MAFLD in mice. LEAP2-KO and wild-type littermate mice were fed a Gubra-Amylin-NASH (GAN) diet for 10 or 40 wks, with some randomized to an additional 28 or 10 days of GAN diet, respectively, while treated with LA-LEAP2 vs Vehicle. Various metabolic parameters were followed and biochemical and histological assessments of MAFLD were made. ResultsAmong the most notable metabolic effects, daily LA-LEAP2 administration to both LEAP2-KO and wild-type littermates during the final 4 wks of a 14 wk-long GAN diet challenge markedly reduced liver weight, hepatic triglycerides, plasma ALT, hepatic microvesicular steatosis, hepatic lobular inflammation, NASH activity scores, and prevalence of higher-grade fibrosis. These changes were accompanied by prominent reductions in body weight, without effects on food intake, and reduced plasma total cholesterol. Daily LA-LEAP2 administration during the final 10 d of a 41.5 wk-long GAN diet challenge also reduced body weight, plasma ALT, and plasma total cholesterol in LEAP2-KO and wild-type littermates and prevalence of higher grade fibrosis in LEAP2-KO mice. ConclusionsAdministration of LA-LEAP2 to mice fed a MAFLD-prone diet markedly improves several facets of MAFLD, including hepatic steatosis, hepatic lobular inflammation, higher-grade hepatic fibrosis, and transaminitis. These changes are accompanied by prominent reductions in body weight and lowered plasma total cholesterol. Taken together, these data suggest that LEAP2 analogs such as LA-LEAP2 hold promise for the treatment of MAFLD and obesity.

Novel Synthesis of Phytosterol Ferulate Using Acidic Ionic Liquids as a Catalyst and Its Hypolipidemic Activity.

Phytosterol ferulate (PF) is quantitively low in rice, corn, wheat, oats, barley, and millet, but it is potentially effective in reducing plasma lipids. In this study, PF was synthesized for the first time using acidic ionic liquids as a catalyst. The product was purified, characterized using Fourier transform infrared, mass spectroscopy, and nuclear magnetic resonance, and ultimately confirmed as the desired PF compound. The conversion of phytosterol surpassed an impressive 99% within just 2 h, with a selectivity for PF exceeding 83%. Plasma lipid-lowering activity of PF was further investigated by using C57BL/6J mice fed a high-fat diet as a model. Supplementation of 0.5% PF into diet resulted in significant reductions in plasma total cholesterol, triacylglycerols, and nonhigh-density lipoprotein cholesterol by 13.7, 16.9, and 46.3%, respectively. This was accompanied by 55.8 and 36.3% reductions in hepatic cholesterol and total lipids, respectively, and a 22.9% increase in fecal cholesterol excretion. Interestingly, PF demonstrated a higher lipid-lowering activity than that of its substrates, a physical mixture of phytosterols and ferulic acid. In conclusion, an efficient synthesis of PF was achieved for the first time, and PF had the great potential to be developed as a lipid-lowering dietary supplement.

Immature carob pods extract and its fractions prevent lipid metabolism disorders and lipoprotein-rich plasma oxidation in mice: A phytochemical and pharmacological study

Ethnopharmacological relevance: In Morocco carob fruits are used traditionally to treat hypercholesterolemia, diabetes and related diseases. Aims: This study was designed to evaluate the hypolipidemic activity of Ceratonia siliqua green pods extract and its fractions in Triton WR-1339 and high fat/cholesterol diet (HFCD) induced hyperlipidemia mice, as well as their ability to prevent lipoproteins oxidation in vitro. Materials and methods: High performance liquid chromatography (HPLC) analysis was used to determine the phenolic composition of the immature carob pods extract (HWCE). Antioxidant activities were evaluated using the DPPH radical scavenging test as well as MDA measurement in oxidized lipoprotein rich plasma. Plasma lipids, glucose and biliary total cholesterol, as well as lipids level in liver and feces, were analyzed. The acute oral toxicity was performed in mice single dosed with the HWCE at 2000 and 5000 mg/kg body weight. Results: HPLC analysis shows that gallic acid is the main phenolic compound in the HWCE. The acute oral toxicity assessment revealed that the HWCE is not toxic (LD50 is greater than 5000 mg/kg body weight). In the acute hypolipidemic study, mice treated with the HWCE and its fractions exhibited a significant (P < 0.001) reduction in plasma total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) levels. Importantly, immature carob aqueous extract was more effective in lowering mice hypercholesterolemia than its fractions. Indeed, mice fed the HFCD for 12 weeks showed a significant raise in plasma TC, TG and LDL-C, as well as in hepatic and fecal TC and TG levels. The HWCE at 100 and 200 mg/kg body weight significantly (P < 0.001) reversed the plasmatic levels of these lipid parameters, increased plasma HDL-C level, reduced hepatic lipids accumulation, but increased cholesterol level in the bile and fecal lipids excretion. The HWCE decreased also the atherogenic index, the LDL-C/HDL-C ratio and plasma glucose level after 12 weeks’ experiment. On the other hand, the HWCE was more effective in preventing mice lipoprotein-rich plasma oxidation than its fractions, with a concentration-dependent manner. Conclusion: C. siliqua green fruits extract could be effective in preventing atherosclerosis and related cardiovascular complications through the inhibition of lipoprotein oxidation and cholesterol clearance.

Effect of endo-1,4-beta-xylanase supplementation to low-energy diets on performance, blood constituents, nutrient digestibility, and gene expressions related growth of broiler chickens.

The presence of soluble and insoluble non-starch polysaccharides (NSP) was reported to reduce nutrient utilisation, and adversely impact the broilers' growth performance; accordingly, NSP-degrading enzymes are essential supplements to cereal-based diets. Therefore, the current trial was conducted to characterise the impacts of supplemental xylanase (Xyl) to diets with low-ME levels on performance, carcass traits, blood parameters, nutrient digestibility and some genes expressions in broiler chickens. A total of 600 1-day-old Ross 308 male broiler chicks were randomly assigned to 6 treatments with 10 replications of 10 birds each per group in a completely randomised design. The 6 treatments were as follow: (1) basal diets with balanced ME content served as control (positive control, PC), (2) low-energy diet (negative control 1 [NC1]; ME content reduced by 70 kcal/kg compared with PC), (3) low-energy diet (negative control 2 [NC2]; ME content reduced by 140 kcal/kg compared with PC), (4) NC1 + 100 g/ton xylanase (NC1 + 100Xyl), (5) NC2 + 100 g/ton xylanase (NC2 + 100Xyl), and (6) NC1 + 50 g/ton xylanase (NC1 + 50Xyl). At the end of the experiment (35 days of age), the reduction of energy in the NC diets yielded lower live body weight (BW) and total body weight gain (BWG) (p ˂ 0.001); however, it significantly increased feed intake (p ˂ 0.05), leading to worst feed conversion ratio (FCR) and European production efficiency factor (EPEF) (p ˂ 0.01) than PC. There was non-significant variation in final BW, BWG, FCR, or EPEF between the PC group and the NC groups supplemented with Xyl. Carcass yield, gizzard, liver and, muscle relative weights were not influenced by dietary treatments; while broilers fed diet with low-energy diets with or without Xyl addition had lower abdominal fat (p ˂ 0.01) than PC. Furthermore, broilers fed on low-ME diets supplemented with Xyl showed a reduction in plasma total cholesterol (p ˂ 0.05) and low density lipoprotein (p ˂ 0.01) levels. Greater antibody titre against Newcastle disease (p ˂ 0.05) was recorded in the NC1 + 100Xyl and NC2 + 100Xyl groups. The addition of Xyl to low-energy diets significantly improved (p ˂ 0.05) fibre digestibility compared to the PC group. Moreover, enzyme supplementation increased muscle total lipids content and decreased muscle thiobarbituric acid retroactive substance content. In addition, enzyme supplementation increased gene expression related to growth and gene expression related to fatty acid synthesis. It was concluded that a low-ME diet might diminish broiler performance, whereas Xyl supplementation to low-ME diets beneficially affected growth performance, abdominal fat percentage, nutrient digestibility and immunity for broilers, and gene expressions related to growth and fatty acid synthesis in broiler chickens fed low-energy diets.

Implications on growth performance, glucose metabolism, PI3K/AKT pathway, intestinal flora induced by dietary taurine in a high-carbohydrate diet for grass carp (Ctenopharyngodon idella).

An 8-week experiment was performed to investigate the influence on growth performance, plasma biochemistry, glucose metabolism and the insulin pathway of supplementation of dietary taurine to a high-carbohydrate diet for grass carp. In this study, fish were fed diets at one of two carbohydrate levels, 31·49 % (positive control) or 38·61 % (T00). The high-carbohydrate basal diet (T00), without taurine, was supplemented with 0·05 % (T05), 0·10 % (T10), 0·15 % (T15) or 0·20 % (T20) taurine, resulting in six isonitrogenous (30·37 %) and isolipidic (2·37 %) experimental diets. The experimental results showed that optimal taurine level improved significantly weight gain, specific growth rate (SGR), feed utilisation, reduced plasma total cholesterol levels, TAG and promoted insulin-like growth factor level. Glucokinase, pyruvate kinase and phosphoenolpyruvate carboxykinase activities showed a quadratic function model with increasing dietary taurine level, while hexokinase, fatty acid synthetase activities exhibited a positive linear trend. Optimal taurine supplementation in high-carbohydrate diet upregulated insulin receptor (Ir), insulin receptor substrate (Irs1), phosphatidylinositol 3-kinase (pi3k), protein kinase B (akt1), glycogen synthase kinase 3 β (gs3kβ) mRNA level and downregulated insulin-like growth factor (igf-1), insulin-like growth factor 1 receptor (igf-1R) and Fork head transcription factor 1 (foxo1) mRNA level. The above results suggested that optimal taurine level could improve growth performance, hepatic capacity for glycolipid metabolism and insulin sensitivity, thus enhancing the utilisation of carbohydrates in grass carp. Based on SGR, dietary optimal tributyrin taurine supplementation in grass carp was estimated to be 0·08 %.

Loquat fruit peel extract regulates lipid metabolism and liver oxidative stress in mice: In vivo and in silico approaches.

In Moroccan traditional medicine, fresh or dried loquat (Eriobotrya japonica (Thunb.) Lindl.) fruit peels infused in water and taken for 45 days are used as natural remedies against hypercholesterolemia, hyperglycemia and cardiovascular diseases. This is the first experimental study approving the folk medicinal use of loquat fruit peels originated from eastern Morocco. The study aims to investigate the effect of loquat fruit peel extract on lipid metabolism and liver oxidative status in mice as well as to predict the possible mechanisms. The study was carried out using high fat/fructose diet-induced hyperlipidemic mice model treated with the loquat peel extract for 45 days at two doses (100 and 200mg/kg/day) in comparison to fenofibrate drug. The plasma, tissue, fecal and biliary lipids and blood glucose were analyzed using enzymatic methods. The liver oxidative status was evaluated and the polyphenol profiling was conducted using the HPLC-DAD method. Possible mechanisms involved in the observed pharmacological effects were predicted by in silico method. The extract at a dose of 200mg/kg possessed higher effect than at 100mg/kg. It significantly reduced plasma total cholesterol (TC), triglycerides (TG), LDL-cholesterol, atherogenic index, LDL-C/HDL-C ratio and plasma glucose (-36%, -45%, -45%, -82%, -87%, 58%, respectively), while the HDL-cholesterol was increased (+172%). Moreover, the extract reduced TC and TG in the liver and adipose tissue by increasing their excretion in bile and fecal matter. It prevented the liver oxidative stress and decreased body weight and organ relative mass. The extract appears to be nontoxic (LD50>5000mg/kg) and contains five polyphenols including ferulic acid (32.74±0.71mg/g), caffeic acid (21.48±0.32mg/g), 5-O-Caffeoylquinic acid (112.15±1.86mg/g), chlorogenic acid (42.05±0.92mg/g) and quercetin (32.69±0.68mg/g). These phenolics and/or their circulating metabolites presented differential interaction capacities with the potential enzymes and transcription factors implicated in lipid homeostasis such as HMG-CoA reductase, lipoprotein lipase, fatty acid synthase, Cyp7a1, ABCG, PPARs, RXR, FXR and RAR. Our findings justify the traditional use of loquat fruit peels and suggest that their aqueous extract could be used as substrate to produce phytotherapeutic drugs or dietary supplements to prevent hyperlipidemia, hyperglycemia and related cardiovascular diseases.

Angiopoietin-like proteins inhibitors: New horizons in the treatment of atherogenic dyslipidemia and familial hypercholesterolemia.

Angiopoietin-like proteins (ANGPTL) are involved in the regulation of numerous physiological and biochemical processes. ANGPTL3, 4 and 8, which are involved in the regulation of lipoprotein metabolism, are particularly important. ANGPTL3, 4 and 8 have been shown to regulate triglyceride availability depending on the nutritional status of the body. In addition, a deficiency of these proteins has been found to cause hypolipidemia (reduction of all lipid fractions). Increases in ANGPTL3, 4 and 8 appear to be associated with cardiovascular risk. Animal studies indicate that the use of ANGPTL3 (evinacumab) inhibitors significantly reduces plasma total cholesterol, triglycerides and low-density lipoprotein concentrations. The use of evinacumab in clinical trials also led to the normalization of plasma lipid concentrations in patients with atherogenic dyslipidemia and homozygous familial hypercholesterolemia. The results of these studies indicate that evinacumab may in the future be used in the treatment of lipid disorders, especially those with hypertriglyceridemia.

The effects of Ginger (Zingiber officinale) roots on the reproductive aspects in male Japanese Quails (Coturnix coturnix japonica)

BackgroundThe Japanese quail is considered one of the most significant species in the poultry industry. However, the high male-to-female ratio results in the aggressive behavior of males. Dietary strategies that improve the properties of semen could reduce the number of males required to maintain optimal fertility and reduce aggressive behavior. Therefore, this study aims to provide insight into the possible improving efm fect of ginger roots on the reproductive aspects of Japanese male quails.ResultsTo achieve this objective, powder of Ginger roots was administrated to 2 groups of quails (10, and 15 g/Kg feed) from 7 days until 70 days of age. Some males were reared singly in cages (n = 40 for each group) to assess sperm quality and other males (n = 32 for each group) were raised with females to assess fertility and sperm-egg penetration. Additionally, biochemical tests and histological examination were also performed. When compared to the control group, dietary inclusion of Ginger at a dose of 15 g caused more improvement in ejaculate volume, sperm concentration, motility, viability and sperm-egg penetration. Whereas, the motility and fertility percentages of sperms were equipotent in both doses. Dose-dependent increases were found in the cloacal gland area and volume, as well as foam production and weight. Both doses resulted in a significant reduction in plasma total cholesterol along with an elevation cin plasma testosterone and lipid peroxides. The comparison between all groups concerning nitric oxide, catalase, superoxide dismutase, and total antioxidant capacity revealed the absence of significant difference. Morphologically, the diameter of the seminiferous tubules and the height of germinal epithelium significantly increased especially in the higher dose of Ginger.ConclusionsGinger roots especially at a dose of 15 gm/kg feed was effective in improving male reproductive performance. These findings are of utmost importance in encouraging the addition of Ginger roots in ration formulation in male quails.

Comparison of protective effects of hesperetin and pectolinarigenin on high-fat diet-induced hyperlipidemia and hepatic steatosis in Golden Syrian hamsters.

A comparative study was conducted to determine whether hesperetin and pectolinarigenin could lower total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) in a high-fat diet (HFD)-induced high lipid model in Golden Syrian hamsters. 48 Golden Syrian hamsters (8 weeks old) were fed with a HFD for 15 days. HFD induced significant increases in plasma TC, TG, LDL, and HDL. Then, these high lipid hamsters were divided into four groups and were administered with 0.5% sodium carboxymethyl cellulose (CMC-Na), hesperetin (100 mg/kg/day), pectolinarigenin (100 mg/kg/day) or atorvastatin (1.0 mg/kg/day), for 7 weeks. It was found that pectolinarigenin treatment resulted in significant reductions in body weight, adiposity index, serum levels of TC, TG and hepatic TC, TG and free fatty acid compared to those in control hamsters with hyperlipidemia (P<0.05). However, hesperetin treatment only caused reductions in plasma TC and hepatic TG levels. Besides, the hamsters treated with pectolinarigenin showed a relatively normal hepatic architecture compared to the hepatic steatosis shown in the control group. Moreover, the expressions of fatty-acid synthase (Fasn) and solute carrier family 27 member 1 (Slc27a1) involved in lipid biosynthesis, were suppressed in the pectolinarigenin-treated groups, and the expression of carnitine palmitoyltransferase 1A (Cpt1a) involved in fatty acid oxidation was increased in the pectolinarigenin-treated group. Taken together, these results suggest pectolinarigenin exerts stronger protective effects against hyperlipidemia and hepatic steatosis than hesperetin, which may involve the inhibition of lipid uptake and biosynthesis.

Plasma Cholesterol- and Body Fat-Lowering Effects of Chicken Protein Hydrolysate and Oil in High-Fat Fed Male Wistar Rats.

Rest raw materials provide a new source of bioactive dietary ingredients, and this study aimed to determine the health effects of diets with chicken protein hydrolysate (CPH) and chicken oil (CO) generated from deboned chicken meat. Male Wistar rats (n = 56) were divided into seven groups in three predefined sub-experiments to study the effects of protein source (casein, chicken fillet, pork fillet, and CPH), the dose-effect of CPH (50% and 100% CPH), and the effects of combining CPH and CO. Rats were fed high-fat diets for 12 weeks, and casein and chicken fillet were used as controls in all sub-experiments. While casein, chicken-, or pork fillet diets resulted in similar weight gain and plasma lipid levels, the CPH diet reduced plasma total cholesterol. This effect was dose dependent and accompanied with the reduced hepatic activities of acetyl-CoA carboxylase and fatty acid synthase. Further, rats fed combined CPH and CO showed lower weight gain, and higher hepatic mitochondrial fatty acid oxidation, plasma L-carnitine, short-chain acylcarnitines, TMAO, and acetylcarnitine/palmitoylcarnitine. Thus, in male Wistar rats, CPH and CO lowered plasma cholesterol and increased hepatic fatty acid oxidation compared to whole protein diets, pointing to potential health-beneficial bioactive properties of these processed chicken rest raw materials.

Short- and long-term complications after living donor ileal resection

Intestinal transplantation from deceased donors is the established procedure for patients with irreversible intestinal failure. However, a living-donor intestinal transplant has not been routinely performed yet because of undefined surgical risks to the donor. In this report, we reviewed our experience with living-donor ileal resection from May 1999 to December 2021. A total of 40 living-donor ileal resections were performed for 40 intestinal transplant recipients. Clinical data were prospectively collected and analyzed for postoperative complications after ileal procurement. None of the donors experienced life-threatening complications or mortality. Six (15%) of 40 donors experienced minor operative complications. Transit intestinal graft inadequacy including weight loss, diarrhea, and vitamin B12 deficiency was common early following surgery, but was manageable and disappeared in most cases within a year. All donors had significant reductions in total plasma cholesterol and low-density lipoprotein cholesterol concentrations after donation as compared with the baseline levels. With an average follow-up of 67.8months, bilateral kidney stones occurred in one donor and gallstones in the other. All the donors have regained their normal capacity for work. Living-donor ileal resection is associated with minimal short- and long-term morbidity and remains an attractive alternative for potential recipients when suitable deceased donors are unavailable.

Pulse Supplementation Improves Gut Health and Lowers Total Cholesterol in Postmenopausal Women

ObjectivesMenopause is associated with many physiological changes as well as increased risk of obesity, cardiovascular disease, type 2 diabetes, and gut-related diseases (i.e. irritable bowel syndrome, inflammatory bowel disease, colon cancer). Data regarding the use of pulse crops in alleviating health risks associated with menopause are limited. This study investigated the effects of pulse supplementation on markers of gut health and metabolic outcomes in postmenopausal women. MethodsThirty-five postmenopausal (≥1 year without menstruation) women, ages 45–70 years old, who were not on hormone replacement therapy, probiotics, antibiotics, multiple supplements, or medications that affect lipids or glucose, were recruited for this clinical study. Study participants were asked to consume 100 g of pulses (alternate between chickpeas, kidney beans, pinto beans, black-eyed peas, and lentils) daily for 12 wks, and to maintain their normal diet and lifestyle. Anthropometric measures including body composition by dual-energy X-ray absorptiometry, plasma lipids and glucose, fecal short chain fatty acids (SCFAs), and stool characteristics (Bristol Stool Chart and the Cleveland Clinic Constipation Scoring System) were assessed before and at the end of 12-wk supplementation. P < 0.05 was considered statistically significant. ResultsThere were no differences in anthropometric measures and plasma glucose at the end of the 12-wk supplementation compared to baseline. However, a reduction in plasma total cholesterol (p = 0.039) and LDL-C (p = 0.026), but an increase in both VLDL-C (p = 0.031) and triglycerides (p = 0.033) were observed with pulse supplementation. Constipation score significantly improved (p = 0.003) but no change in stool quality were observed with pulse supplementation. Fecal acetic acid (p< 0.001), n-butyric (p = 0.038), n-caproic (p = 0.004) and total SCFAs (p = 0.001) were also significantly increased with pulse supplementation. ConclusionsOur findings demonstrate that 12 wks of pulse supplementation improved markers of gut health and lowers total- and LDL-cholesterol in postmenopausal women. This population who are at an increased risk for cardiovascular and gut-related diseases can benefit from regularly consuming pulses. Funding SourcesUSDA Award Pulse Crop Health Initiative (#58-3060-0-048) and the Jim and Lynn Williams Professorship

The Effects of Exercise on Plaque Volume and Composition in a Mouse Model of Early and Late Life Atherosclerosis.

BackgroundExercise is associated with a less atherogenic lipid profile; however, there is limited research on the effect of exercise on atherosclerotic plaque composition and markers of plaque stability.MethodsA total of 110 apolipoprotein (apo)E−/− mice were placed on a chow diet and randomly assigned to control or exercise for a period of 10 weeks, commencing either at 12 weeks of age (the early-stage atherosclerosis, EA group) or at 40 weeks of age (the late-stage atherosclerosis, LA group). At the end of the exercise period, blood was assayed for lipids. Histologic analysis of the aortic sinus was undertaken to assess plaque size and composition that includes macrophage content, monocyte chemoattractant protein (MCP)-1, matrix metalloproteinase-2 (MMP-2), and tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and 2).ResultsA total of 103 mice (38 EA, 65 LA) completed the protocol. In the EA group, exercise reduced plasma total cholesterol (TC) (−16%), free cholesterol (−13%), triglyceride (TG) (−35%), and phospholipid (−27%) levels, when compared to sedentary control mice (p < 0.01). In the EA group, exercise also significantly reduced plaque stenosis (−25%, p < 0.01), and there were higher levels of elastin (3-fold increase, p < 0.0001) and collagen (11-fold increase, p < 0.0001) in plaques, compared to control mice. There was an increase in plaque MMP-2 content in the exercise group (13% increase, p < 0.05) but no significant difference in macrophage or MCP-1 content. In the LA group, exercise reduced plaque stenosis (−18%, p < 0.05), but there was no significant difference in plaque composition. There was no difference in macrophage, MCP-1, or MMP-2 content in the LA groups. TIMP-1 was lower with exercise in both the EA and LA groups (−59%, p < 0.01 and −51%, p < 0.01 respectively); however, there was no difference in TIMP-2 levels.ConclusionA 10-week exercise period reduces atherosclerotic plaque stenosis when commenced at both early- and late-stage atherosclerosis. Intervening earlier with exercise had a greater beneficial effect on lipids and plaque composition than when starting exercise at a later disease stage.

Effects of replacing fishmeal with methanotroph (Methylococcus capsulatus, Bath) bacteria meal (FeedKind®) on growth and intestinal health status of juvenile largemouth bass (Micropterus salmoides)

A ten-week feeding trial evaluated the feasibility of methanotroph (Methylococcus capsulatus) bacteria meal (FeedKind®, FK) as a fishmeal substitute in largemouth bass (Micropterus salmoides) diets. Six isonitrogenous and isoenergetic diets with different inclusion levels of FK (0 (fishmeal group), 43, 86, 129, 172 and 215 g/kg) were formulated to replace 0, 50, 100, 150, 200 and 250 g/kg fishmeal, respectively. The results showed that FK inclusion level could reach 129 g/kg without significantly affecting growth or feed coefficient rate (P > 0.05), while growth performance was decreased and feed coefficient rate increased when FK inclusion levels exceeded 129 g/kg (P < 0.05). Increase in FK inclusion levels tended to reduce plasma total cholesterol and total triglyceride whilst plasma total protein, albumin, alanine aminotransferase and aspartate aminotransferase in FK treatment groups were unchanged compared with fishmeal group (P > 0.05). FK inclusion levels at 43 g/kg and 86 g/kg were not detrimental to intestinal morphology whilst it was unfavourable when FK inclusion levels exceeded 86 g/kg as the total length of intestinal wall thickness and villus height, villus height were obviously decreased compared with fishmeal group (P < 0.05). As regards to inflammatory cytokine genes, FK instead of fishmeal increased the expression levels of TLR2, RelA, TNF-α, IL-1β, IL-10 and TGF-β, 43 g/kg and 86 g/kg FK decreased the expression level of Caspase-3 (P < 0.05). In conclusion, 129 g/kg FK can replace 150 g/kg fishmeal without negative effects on the growth performance, and replacing 100 g/kg fishmeal with 86 g/kg FK is more beneficial to intestinal health.

Peony seed oil decreases plasma cholesterol and favorably modulates gut microbiota in hypercholesterolemic hamsters.

Peony (Paeonia spp.) seed oil (PSO) contains a high amount of α-linolenic acid. The effects of PSO on hypercholesterolemia and gut microbiota remains unclear. The present study was to investigate effects of PSO supplementation on cholesterol metabolism and modulation of the gut microbiota. Male Golden Syrian hamsters (n = 40) were randomly divided into five groups (n = 8, each) fed one of the following diets namely low-cholesterol diet (LCD); high cholesterol diet (HCD); HCD with PSO substituting 50% lard (LPSO), PSO substituting 100% lard (HPSO) and HCD with addition of 0.5% cholestyramine (PCD), respectively, for 6weeks. PSO supplementation dose-dependently reduced plasma total cholesterol (TC) by 9-14%, non-high-density lipoprotein cholesterol (non-HDL-C) by 7-18% and triacylglycerols (TG) by 14-34% (p < 0.05). In addition, feeding PSO diets reduced the formation of plaque lesions by 49-61% and hepatic lipids by 9-19% compared with feeding HCD diet (p < 0.01). PSO also altered relative genus abundance of unclassified_f__Coriobacteriaceae, unclassified_f__Erysipelotrichaceae, Peptococcus, unclassified_f__Ruminococcaceae, norank_o__Mollicutes_RF9 and Christensenellaceae_R-7_group. It was concluded that PSO was effective in reducing plasma cholesterol and hepatic lipids and favorably modulating gut microbiota associated with cholesterol metabolism.

Plasma lathosterol measures rates of cholesterol synthesis and efficiency of dietary phytosterols in reducing the plasma cholesterol concentration

Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol, the authors investigated whether the plasma Phytosterols (PS) relate to the body's cholesterol synthesis rate measured as non-cholesterol sterol precursors (lathosterol). The authors studied38non-obese volunteers (58±12years; Low-Density Lipoprotein Cholesterol ‒ LDL-C≥ 130mg/dL) randomly assigned to consume 400mL/day of soy milk (Control phase) or soy milk+PS (1.6 g/day) forfourweeks in a double-blind, cross-over study. PS and lathosterol were measured in plasma by gas chromatography coupled to mass spectrophotometry. PS treatment reduced plasma total cholesterol concentration (-5.5%, p<0.001), LDL-C (-7.6%, p<0.001), triglycerides (-13.6%, p<0.0085), and apolipoprotein B (apoB) (-6.3%, p<0.008), without changing high density lipoprotein cholesterol (HDL-C concentration), but plasma lathosterol, campesterol and sitosterol expressed per plasma cholesterol increased. The lathosterol-to-cholesterol plasma ratio predicted the plasma cholesterol response to PS feeding. The highest plasma lathosterol concentration during the control phase was associated with a lack of response of plasma cholesterol during the PS treatment period. Consequently, cholesterol synthesis in non-responders to dietary PS being elevated in the control phase indicates these cases resist to further synthesis rise, whereas responders to dietary PS, having in the control phase synthesis values lower than non-responders, expand synthesis on alimentary PS. Responders absorb more PS than non-responders, likely resulting from responders delivering into the intestinal lumen less endogenous cholesterol than non-responders do, thus facilitating greater intestinal absorption of PS shown as increased plasma PS concentration.

Supplementation of omega-3 and dietary factors can influence the cholesterolemia and triglyceridemia in hyperlipidemic Schnauzer dogs: A preliminary report.

Primary hyperlipidaemia in Schnauzer is characterized by increased plasma triglycerides (TG) and/or total cholesterol (TC) concentration and is associated with an increased risk of developing pancreatitis, insulin resistance and seizures. In humans, omega-3 fatty acids in addition to a low-fat diet can be used to reduce TG and TC. This study evaluated the therapeutic efficacy of omega-3 fatty acids associated to a diet management with two different fat content in Schnauzer with primary hyperlipidaemia. Eighteen dogs with primary hyperlipidaemia were divided into two groups: group 1, n = 10, 8 females, 2 males, age (mean ± standard deviation) of 7.13 ± 2.70 years and body weight (BW) (mean ± standard deviation) of 7.25 ± 1.22 kg were treated with fish oil (approximately 730 mg/day of omega-3) associated with a low-fat and low-calorie diet (approximately 24g of fat/1000 kcal) for 90 days (T90); and group 2, n = 8 dogs, 6 females, 2 males, with 7.0 ± 1.77 years old and average BW of 8.36 ± 1.51 kg, treated with fish oil (approximately 730 mg/day of omega-3) and maintenance diet with moderate amount of fat (approximately 33g of fat/1000 kcal) for 90 days. Plasma TG and TC concentrations and lipoprotein (LP) profile (VLDL, LDL, HDL) were evaluated before and after treatment. TG and TC serum concentrations, expressed in mg/dL (mean ± standard deviation), before and after treatment in group 1 were: TG = 391.30 ± 487.86 (T0) and 118.7 ± 135.21 (T90); TC = 308.2 ± 63.06 (T0) and 139 ± 36.91 (T90). As for group 2, TG = 391.63 ± 336.89 (T0) and 250.75 ± 211.56 (T90); TC = 257.25 ± 92.88 (T0) and 207.25 ± 63.79 (T90). A reduction (p<0.05) of TG and TC was observed in both groups. The distribution of TG and TC among LP was not different between the pre (T0) and post treatment (T90) periods. After 90 days of treatment, the administration of omega-3 fatty acids, associated with a low-fat or maintenance diet reduced triglyceridemia and cholesterolemia without altering LP profile. The current investigation shows that both therapies were effective in reducing plasma TC and TG concentrations without altering LP profile.

Sweet Potato Leaf Feeding Decreases Cholesterol, Oxidative Stress and Thrombosis Formation in Syrian Hamsters with a High-Cholesterol Diet

Nutritional strategies to reduce hyperlipidemia and the risk of cardiovascular disease are gaining more public favor and medical professionals’ attention. The authors of this study explored the effect of sweet potato leaf powder (SPLP) feeding on the parameters of plasma lipids, reactive oxygen species, and time to thrombosis formation in Syrian hamsters fed with high-cholesterol diets. The animals were separated into six groups: a feeding control diet, a control diet containing 0.1% cholesterol, a control diet containing 0.2% cholesterol, a control diet containing 0.1% cholesterol plus 2.5% SPLP, a control diet containing 0.1% cholesterol plus 5% SPLP, and a control diet containing 0.2% cholesterol plus 5% SPLP for six weeks. The levels of serum total cholesterol (51% increase), low-density lipoprotein cholesterol (70.6% increase), very-low-density lipoprotein cholesterol (51.3% increase), and the triglyceride and atherogenic index (LDL-C/HDL-C) significantly increased in the high-cholesterol diet groups. Concomitant 5% sweet potato leaf powder ingestion significantly decreased the lipid profiles, with a 20.6% total cholesterol reduction in the 0.1% cholesterol diet groups, a 17.2% reduction in the 0.2% group, a 48.7% LDL reduction in the 0.1% cholesterol group, and a 30.3% reduction in the 0.2% group, with a consequent decrease in the atherogenic index. SPLP feeding was found to be associated with increased fecal sterol contents, with a 188.6% increase in the 0.1% cholesterol-fed group and a 177.3% increase in the 0.2% group. The SPLP-fed groups had depressed ROS levels, elongated FeCl3-induced times to thrombosis formation, and increased liver superoxide dismutase contents and SREBP-1 protein expression. Sweet potato leaf intake could reduce plasma total cholesterol, LDL, and oxidative stress. We suggest sweet potato leaf intake as a choice of nutritional strategy for hyperlipidemia and cardiovascular disease prevention.

Effect of phytosterols in the treatment of hypercholesterolemia in adults – systematic review with meta-analysis / Efeitos dos fitoesteróis no tratamento da hipercolesterolemia em adultos – revisão sistemática com metanálise

Increased plasma total cholesterol (TC) and LDL-cholesterol (low-density lipoprotein) are considered risk factors for coronary disease. Phytosterols are among the dietary options for decreasing serum concentrations of TC and LDL-c by up to 15%.To evaluate the scientific evidence on the use of phytosterols in the treatment of hypercholesterolemia in adults.A systematic meta-analysis of the Medline, Embase, Web of Service, VHL, PUBMED, Scopus, Cochrane Library and LILACS databases was performed between November and December 2016. The PICO strategy was used. Inclusion criteria were randomized clinical trials with adults of both sexes using phytosterols longer than 4 weeks intervention. Exclusion criteria were animal and in vitro studies, humans less than 18 years old and individuals with other diseases (cancer, metabolic syndromes, diabetes mellitus, hypertension, renal disease, liver diseases). The risk of bias was assessed by two reviewers. The primary outcomes investigated were TC and LDL-cholesterol. Statistical analyses were conducted using the RevMan 5.3. The standardized effect size was used to estimate the standardized mean difference and 95% CI of TC and LDL-c.Twenty-seven randomized controlled trials were included in this systematic review and 26 studies in the meta-analysis of TC and LDL-cholesterol. The meta-analyzes showed an association with the reduction in plasma TC (-2.54 [-3.04; -2.03]) and LDL-c (-2.8 [-2.63; -1.53]) after intervention with the vegetable esters.The consumption of 1.5 to 2.0 g/day of phytosterols promotes reduction of TC and LDL-c in hypercholesterolemic individuals, regardless of the way they are consumed.