Cholesterol-lowering Mechanism Research Articles

Enhancement of Intracellular Cholesterol Efflux in Chondrocytes Leading to Alleviation of Osteoarthritis Progression.

Osteoarthritis (OA) is the most common degenerative disease worldwide, with no practical means of prevention and limited treatment options. Recently, our group unveiled a novel mechanism contributing to OA pathogenesis in association with abnormal cholesterol metabolism in chondrocytes. In this study, we aimed to establish a clinical link between lipid profiles and OA in humans, assess the effectiveness of cholesterol-lowering drugs in suppressing OA development in mice, and uncover the cholesterol-lowering mechanisms that effectively impede OA progression. Five clinically approved cholesterol-lowering drugs (fenofibrate, atorvastatin, ezetimibe, niacin, and lomitapide) were injected into the knee joints or administered with diet to mice with OA who underwent destabilization of the medial meniscus induction and were fed a 2% high-cholesterol diet. Gene expression linked to cholesterol metabolism was determined using microarray analysis. Furthermore, the in vivo functions of these genes were explored through intra-articular injection of either its inhibitor or adenovirus. Logistic regression analysis confirmed a close relationship between the diagnostic criteria of hyperlipidemia based on serum lipid levels and OA incidence. Among the cholesterol-lowering drugs examined, fenofibrate exerted the most significant protective effect against cartilage destruction, which was attributed to elevated levels of high-density lipoprotein cholesterol that are crucial for cholesterol efflux. Notably, cholesterol efflux was suppressed during OA progression via down-regulation of apolipoprotein A1-binding protein (AIBP) expression. Overexpression of AIBP effectively inhibits OA progression. Our results suggest that restoration of cholesterol homeostasis to a normal state through administration of fenofibrate or AIBP overexpression, both of which induce cholesterol efflux, offers an effective therapeutic option for patients with OA.

β-Glucan content and in vitro bile-acid binding capacity of Agaricus bisporus and Pleurotus spp.

The cholesterol lowering properties of oats and barley, attributed to their high β-glucan content, are well established, but it remains unclear whether mushrooms, also rich in β-glucan, exhibit a similar functionality. We aimed to quantify the β-glucan content of commonly consumed Australian mushrooms and evaluated their bile acid binding capacity, the primary cholesterol lowering mechanism of β-glucan. Raw, boiled and fried Australian grown Agaricus bisporus (button, cup, flat and brown mushrooms) and Pleurotus spp. (shimeji and oyster) along with oats were freeze-dried and the β-glucan content was determined. The bile acid binding capacity of these samples was assessed using an in vitro digestion assay. The β-glucan content of freeze-dried raw A. bisporus mushrooms (4.5-8.1 g per 100 g) was similar to that of oats (7.6 g per 100 g, all p > 0.05), whereas Pleurotus mushrooms contained ∼5 times more β-glucan (32.5-37.4 g, p < 0.05). Boiling increased the β-glucan content of oyster, button, flat and brown mushrooms by 3-7% (p < 0.05), but did not affect the β-glucan content of shimeji or cup mushrooms. Frying had no effect on any mushroom type. The bile acid binding capacity of A. bisporus mushrooms (29-36%) was equivalent to that of raw oats (36%, p > 0.05), whereas the bile acid binding capacity of oyster mushrooms (22%) was lower than that of oats (p < 0.05). Both boiling and frying increased the bile acid binding capacity. The cholesterol lowering effects of A. bisporus mushrooms and the acceptability of consumption at the required levels need to be confirmed by clinical trials.

Cholesterol lowering in diet-induced hypercholesterolemic mice using Lactobacillus bile salt hydrolases with different substrate specificities.

The cholesterol-lowering effect of lactic acid bacteria with high activity of bile salt hydrolase (BSH) is unclear. We believe that distinguishing BSH substrate specificity is necessary to study the effect of various BSH enzymes. We engineered a BSH mutant enzyme recombinant strain named F67A, which exclusively hydrolyzes taurocholic acid (TCA) using site-directed mutagenesis, and a previously lab-constructed BSH recombinant strain, YB81 that exclusively hydrolyzes glycocholic acid (GCA). We also constructed the recombinant strain named NB5462, which carries the empty pSIP411 plasmid and was used as a blank control strain. The intestinal flora in pseudo-germ-free (PGF) mice in which intestinal flora were eliminated via antibiotics, and F67A successfully reduced serum cholesterol levels in high-cholesterol diet-fed mice, whereas YB81 did not yield the same results. However, YB81 regained its cholesterol-lowering capacity in specific pathogen-free (SPF) mice with intact intestinal flora. The cholesterol-lowering mechanism of F67A involved modifying the bile acid pool through BSH enzyme activity. This adjustment regulated the expression of intestinal farnesoid X receptor and subsequently elevated hepatic cholesterol 7α-hydroxylase (CYP7A1), effectively reducing cholesterol levels. Conversely, GCA, the substrate of YB81, was found in minimal quantities in mice, preventing it from inducing changes in bile acid pools. In the presence of intestinal flora, the YB81 BSH enzyme induced notable alterations in bile acids by regulating changes in the intestinal flora and BSH within the flora, ultimately resulting in cholesterol reduction. This is the first study investigating the substrate specificity of BSH, demonstrating that different substrate-specific BSH enzymes exhibit cholesterol-lowering properties. Additionally, we elaborate on the mechanism of BSH-mediated enterohepatic axis regulation.

Regulation of Hepatocellular Cholesterol Metabolism By Lactobacillus Paracasei BY2 and Its Embedding Delivery.

In this study, five strains of lactic acid bacteria (LAB) with excellent cholesterol-lowering ability were screened from fermented foods. The gastrointestinal stress resistance, intestinal adhesion, and bacteriostasis abilities were evaluated to obtain the best LAB. And then, high-cholesterol HepG2 cell model was further prepared to explore the cholesterol-lowering mechanism of the LAB. Finally, pH-sensitive hydrogel prepared by Millettia speciosa Champ. carboxymethyl cellulose and Millettia speciosa Champ. cellulose was first applied to the microencapsulation of LAB. As a result, Lactobacillus paracasei BY2 (LP-BY2) exhibited higher cholesterol-lowering activity, intestinal adhesion, and bacteriostasis abilities compared with other LAB. Furthermore, it was found that LP-BY2 could reduce the cholesterol level by regulating the expression of key genes that involved in cholesterol synthesis (HMGCR and SREBP-2), uptake (LDLR), and outflow (LXR-α, ABCA1, ABCG5, ABCG8, and CYP7A1) in liver. At the same time, microencapsulation significantly enhanced the survival rate and cholesterol-lowering ability of LP-BY2 after gastrointestinal digestion. This study will provide an available reference for the application of Lactobacillus in prevention and treatment of hypercholesterolemia.

Inhibitory Effect of Isoliquiritigenin in Niemann-Pick C1-Like 1-Mediated Cholesterol Uptake.

Isoliquiritigenin (ISL) is a flavonoid with a chalcone structure extracted from the natural herb Glycyrrhiza glabra. Its anti-inflammatory, antibacterial, antioxidant, and anticancer activities have been extensively studied. Moreover, ISL also possess hypolipidemic and atherosclerosis-reducing effects. However, its cholesterol-lowering mechanisms have not been reported yet. Niemann Pick C1 Like 1 (NPC1L1) is a specific transporter of cholesterol uptake. In this study, we found for the first time that ISL downregulates NPC1L1 expression and competitively inhibits cellular cholesterol uptake by binding to NPC1L1 in a concentration-dependent manner in vitro. This study provides a theoretical basis for further investigation of the molecular mechanisms of its cholesterol-lowering effect in vivo and inspired emerging drug research for cholesterol-lowering purposes through NPC1L1 inhibition.

Levilactobacillus brevis from carnivores can ameliorate hypercholesterolemia: In vitro and in vivo mechanistic evidence.

The aim was to explore the probiotic and hypocholesterolaemic potential of two Levilactobacillus brevis strains of carnivore origin along with selected underlying mechanisms. Levilactobacillus brevis MT950194 and L. brevis MW365351 were analysed in vitro for oro-gastro-intestinal stress tolerance, cholesterol reduction, cholesterol adsorption (through scanning electron microscopy) and bile salt hydrolase (BSH) activity. Strains could survive (>80%) in oro-gastro-intestinal conditions and reduce high amount of cholesterol (35% and 54%) from media containing bile salts (0.3%) as compared with Lactobacillus acidophilus ATCC 4356 and presented the least pathogenicity towards mammalian cells. Exopolysaccharide production, cell surface cholesterol adherence and BSH activity were witnessed as possible cholesterol-lowering mechanisms. In in vivo experiment, the treatments of hypercholesterolaemic rats with L. brevis MT950194, L. brevis MW365351 and their mixture led to significant (p< 0.05) reduction in serum and hepatic cholesterol, low-density lipids, cholesterol ratio, liver steatosis and size of adipocytes. It further ameliorated diet-induced changes in hepatic enzymes. Levilactobacillus brevis MT950194 and L. brevis MW365351 from carnivores have probiotic pharmacological potential and can reduce serum cholesterol through surface adherence and BSH production. These strains may be utilized in treating hypercholesterolaemia and production of low-fat functional foods.

Production, Characterization, Delivery, and Cholesterol-Lowering Mechanism of Phytosterols: A Review.

Phytosterols are natural plant-based bioactive compounds that can lower blood cholesterol levels and help prevent cardiovascular diseases. Consequently, they are being utilized in functional foods, supplements, and pharmaceutical products designed to improve human health. This paper summarizes different approaches to isolate, purify, and characterize phytosterols. It also discusses the hypolipidemic mechanisms of phytosterols and their impact on cholesterol transportation. Phytosterols have a low water-solubility, poor chemical stability, and limited bioavailability, which limits their utilization and efficacy in functional foods. Strategies are therefore being developed to overcome these shortcomings. Colloidal delivery systems, such as emulsions, oleogels, liposomes, and nanoparticles, have been shown to be effective at improving the water-dispersibility, stability, and bioavailability of phytosterols. These delivery systems can be used to incorporate phytosterols into a broader range of cholesterol-lowering functional foods and beverages. We also discuses several issues that need to be addressed before these phytosterol delivery systems can find widespread commercial utilization.

Hypoxia inducible factor 1α inhibitor PX-478 reduces atherosclerosis in mice

Background and aimsHypoxia inducible factor 1α (HIF1α) plays a critical role in atherosclerosis as demonstrated in endothelial-targeted HIF1α -deficient mice. However, it has not been shown if specific pharmacological inhibitors of HIF1α can be used as potential drugs for atherosclerosis. PX-478 is a selective inhibitor of HIF1α, which was used to reduce cancer and obesity in animal models. Here, we tested whether PX-478 can be used to inhibit atherosclerosis. MethodsWe first tested PX-478 in human aortic endothelial cells (HAEC) and found that it significantly inhibited expression of HIF1α and its targets, including Collagen I. Next, two independent atherosclerosis models, C57BL/6 mice treated with AAV-PCSK9 and ApoE−/− mice, were used to test the efficacy of PX-478. Both mouse models were fed a Western diet for 3 months with bi-weekly treatment with PX-478 (40 mg/kg) or saline. ResultsPX-478 treatment reduced atherosclerotic plaque burden in the aortic trees in both mouse models, while plaque burden in the aortic sinus was reduced in the AAV-PCSK9 mouse model, but not in the ApoE−/− mice. Russell-Movat's Pentachrome and Picrosirius Red staining showed a significant reduction in extracellular matrix remodeling and collagen maturation, respectively, in the PX-478-treated mice. As expected, PX-478 treatment reduced diet-induced weight-gain and abdominal adipocyte hypertrophy. Interestingly, PX-478 reduced plasma LDL cholesterol by 69% and 30% in AAV-PCSK9 and ApoE−/− mice, respectively. To explore the cholesterol-lowering mechanisms, we carried out an RNA sequencing study using the liver tissues from the ApoE−/− mouse study. We found 450 genes upregulated and 381 genes downregulated by PX-478 treatment in the liver. Further, gene ontology analysis showed that PX-478 treatment upregulated fatty acid and lipid catabolic pathways, while downregulating lipid biosynthesis and plasma lipoprotein particle remodeling processes. Of interest, Cfd, Elovl3, and Insig2 were some of the most downregulated genes by PX-478, and have been implicated in fat storage, fatty acid elongation, and cholesterol metabolism. The downregulation of Cfd, Elovl3, and Insig2 was further validated by qPCR in the liver tissues of ApoE−/− mice treated with PX-478. ConclusionsThese results suggest that PX-478 is a potential anti-atherogenic drug, which targets vascular endothelium and hepatic cholesterol pathways.

Cholesterol-lowering effect of bile salt hydrolase from a Lactobacillus johnsonii strain mediated by FXR pathway regulation.

Hypercholesterolemia is a major risk factor for cardiovascular diseases worldwide. Healthy intestinal microbiota can contribute to reducing the high cholesterol symptoms by producing bile salt hydrolase (BSH). In this study, recombinant BSH from the strain L. johnsonii 334 with high cholesterol reduction ability was selected to study the cholesterol-lowering mechanism mediated by farnesoid X receptor (FXR) regulation in mice. In the presence of recombinant BSH, mice had a larger bile acid pool. Analysis of individual bile acids revealed that bile acid composition was affected not only by recombinant BSH but also by the modulated gut microbiota. We confirmed a marked reduction in the transcription of FXR and its molecular targets in the ileum and a significant increase in the transcription of cholesterol 7a-hydroxylase (CYP7A1), which resulted in the increased bile acid synthesis and cholesterol-lowering effects. Notably, our work reveals the importance of BSH substrate specificity.

The Effects of a High-Fat/Cholesterol Diet on the Intestine of Rats Were Attenuated by Sparassis latifolia Polysaccharides.

Sparassis latifolia polysaccharides can regulate lipids and cholesterol in serum and liver. However, little is known about the regulation mechanism of the polysaccharides on cholesterol metabolism and especially the causal relationship with gut microbiota regulation. This study will provide a theoretical basis for the cholesterol-lowering mechanism of S. latifolia polysaccharides and further development of functional foods. In this study, we investigated how the regulation mechanism of Sparassis latifolia polysaccharides affects intestinal cholesterol metabolism in high-fat and high-cholesterol diet-fed rats. Briefly, enzymatic colorimetric microplate assay was used to determine the concentration of faecal bile acid. Gas chromatography-mass spectrometry was used to detect the content of cholesterol and alcohol in faeces. Haematoxylin and eosin staining method was applied to observe the changes in the structure of the small intestine tissue. The related gene expressions in jejunum and ileum were detected by real-time fluorescent quantitative polymerase chain reaction. The related protein expressions in jejunum were studied by using Western blot. High-throughput sequencing was used to detect the intestinal flora changes of the caecal contents. Gas chromatography-mass spectrometry was applied to detect the concentration of short-chain fatty acids in the caecal content. The results showed that Sparassis latifolia polysaccharides could improve the intestinal morphological structure and physiological indices in rats fed high-fat and high-cholesterol diet. Moreover, it could improve intestinal cholesterol metabolism disorder induced by high-fat and high-cholesterol diets via the reduction of the expression of HMGCR, NPC1L1, ACAT2, MTP, ASBT and IBABP mRNA or protein, increasing ABCG8 mRNA expression. In addition, it could also increase the relative abundance of Bacteroides, Butyricicoccus, Parabacteroides, Parasutteerella and Alloprevotella and the short-chain fatty acid concentration, to comprehensively regulate the intestinal cholesterol metabolism. The metabolomics analysis found that Sparassis latifolia polysaccharides could affect lipid, carbohydrate and other related metabolites. Some biomarkers associated with cholesterol metabolism correlated significantly with the abundance of specific intestinal microbiota. These findings indicate that Sparassis latifolia polysaccharides could attenuate intestinal cholesterol metabolism disorder, correlating with modulating gut microbiota and improving host metabolism. They provide theoretical support for the development of Sparassis latifolia as a new food resource.

Dietary Phospholipids Prepared From Scallop Internal Organs Attenuate the Serum and Liver Cholesterol Contents by Enhancing the Expression of Cholesterol Hydroxylase in the Liver of Mice.

In this study, we successfully prepared scallop oil (SCO), which contains high levels of phospholipids (PL) and eicosapentaenoic acid (EPA), from the internal organs of the Japanese giant scallop (Patinopecten yessoensis), one of the most important underutilized fishery resources in Japan. The intake of SCO lowers the serum and liver cholesterol contents in mice; however, whether the fatty acids (FA) composition or PL of SCO exhibits any cholesterol-lowering effect remains unknown. To elucidate whether the cholesterol-lowering function is due to FA composition or PL of SCO, and investigate the cholesterol-lowering mechanism by SCO, in the present study, mice were fed SCO's PL fraction (SCO-PL), triglyceride (TG)-type oil with almost the same FA composition as SCO-PL, called SCO's TG fraction (SCO-TG), soybean oil (SOY-TG), and soybean's PL fraction (SOY-PL). Male C57BL/6J mice (5-week-old) were fed high-fat and cholesterol diets containing 3% (w/w) experimental oils (SOY-TG, SOY-PL, SCO-TG, and SCO-PL) for 28 days. The SCO-PL diet significantly decreased the serum and liver cholesterol contents compared with the SOY-TG diet, but the intake of SOY-PL and SCO-TG did not show this effect. This result indicated that the serum and liver cholesterol-lowering effect observed in the SCO intake group was due to the effect of SCO-PL. The cholesterol-lowering effect of SCO-PL was in part related to the promotion of liver cholesterol 7α-hydroxylase (CYP7A1) expression, which is the rate-limiting enzyme for bile acid synthesis. In contrast, the expression levels of the ileum farnesoid X receptor (Fxr) and fibroblast growth factor 15 (Fgf15), which inhibit the expression of liver CYP7A1, were significantly reduced in the SCO-PL group than the SOY-TG group. From these results, the increase in the liver CYP7A1 expression by dietary SCO-PL was in part through the reduction of the ileum Fxr/Fgf15 regulatory pathway. Therefore, this study showed that SCO-PL may be a health-promoting component as it lowers the serum and liver cholesterol contents by increasing the liver CYP7A1 expression, which is not seen in SOY-PL and SCO-TG.

Evaluation of the Cholesterol-Lowering Mechanism of Enterococcus faecium Strain 132 and Lactobacillus paracasei Strain 201 in Hypercholesterolemia Rats.

Hypercholesterolemia can cause many diseases, but it can effectively regulated by Lactobacillus. This study aimed to evaluate the cholesterol-lowering mechanism of Enterococcus faecium strain 132 and Lactobacillus paracasei strain 201. These results showed that both the strains decreased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), liver TC and TG and increased fecal TC, TG and total bile acid (TBA) levels. Additionally, both strains also reduced glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST) and levels of tissue inflammation levels to improve the lipid profile, and they reduced fat accumulation partially by alleviating inflammatory responses. Furthermore, both strains regulated the expression of the CYP8B1, CYP7A1, SREBP-1, SCD1 and LDL-R gene to promote cholesterol metabolism and reduce TG accumulation. Interventions with both strains also altered the gut microbiota, and decreasing the abundance of Veillonellaceae, Erysipelotrichaceae and Prevotella. Furthermore, fecal acetic acid and propionic acid were increased by this intervention. Overall, the results suggested that E. faecium strain 132 and L. paracasei strain 201 can alleviate hypercholesterolemia in rats and might be applied as a new type of hypercholesterolemia agent in functional foods.

Lactobacillus delbrueckii Interfere With Bile Acid Enterohepatic Circulation to Regulate Cholesterol Metabolism of Growing-Finishing Pigs via Its Bile Salt Hydrolase Activity.

Microbiota-targeted therapies for hypercholesterolemia get more and more attention and are recognized as an effective strategy for preventing and treating cardiovascular disease. The experiment was conducted to investigate the cholesterol-lowering mechanism of Lactobacillus delbrueckii in a pig model. Twelve barrows (38.70 ± 5.33 kg) were randomly allocated to two groups and fed corn–soybean meal diets with either 0% (Con) or 0.1% Lactobacillus delbrueckii (Con + LD) for 28 days. L. delbrueckii–fed pigs had lower serum contents of total cholesterol (TC), total bile acids (TBAs), and triglyceride, but higher fecal TC and TBA excretion. L. delbrueckii treatment increased ileal Lactobacillus abundance and bile acid (BA) deconjugation and affected serum and hepatic BA composition. Dietary L. delbrueckii downregulated the gene expression of ileal apical sodium-dependent bile acid transporter (ASBT) and ileal bile acid binding protein (IBABP), and hepatic farnesoid X receptor (FXR), fibroblast growth factor (FGF19), and small heterodimer partner (SHP), but upregulated hepatic high-density lipoprotein receptor (HDLR), low-density lipoprotein receptor (LDLR), sterol regulatory element binding protein-2 (SREBP-2), and cholesterol-7α hydroxylase (CYP7A1) expression. Our results provided in vivo evidence that L. delbrueckii promote ileal BA deconjugation with subsequent fecal TC and TBA extraction by modifying ileal microbiota composition and induce hepatic BA neosynthesis via regulating gut–liver FXR–FGF19 axis.

Transcriptional analysis for cholesterol-lowering effects of marine Lactobacillus plantarum Lp10 isolated from kelp

Lactobacillus plantarum, which exerts a variety of probiotic functions, has been recognized as a supplement for human foods with a widespread application. In this work, the cholesterol-lowering mechanisms of marine L. plantarum Lp10 were investigated by combining the analyses of transcriptome and quantitative real-time PCR. Results indicated that bile salt hydrolase (BSH) activity and extracellular polysaccharides (EPSs) adsorption were both responsible for cholesterol reduction. In this process, 11.1 million clean reads and 384 differentially expressed genes, including 79 up-regulated genes and 225 down-regulated genes, were obtained by transcriptome analysis. It was considered that EPS adsorption was mainly responsible for the cholesterol reduction without the influence of bile salt. Further analysis showed that the co-precipitation of cholesterol and deconjugated bile acids induced by BSH1 and BSH2 may play important role in the tolerance and reduction of cholesterol of strain under the stress condition with bile salt, in which, interestingly, the expressions of bsh3 and bsh4 were suppressed. In conclusion, the cholesterol-lowering mechanisms of marine L. plantarum Lp10 was investigated and it was considered as a potential strain for the application in cholesterol reduction.

In-vivo evaluation of tissue scaffolds containing simvastatin loaded nanostructured lipid carriers and mesenchymal stem cells in diabetic wound healing

Efficacy of simvastatin on wound healing and stem cell treatment, in addition to the cholesterol lowering mechanism, has been investigated in recent studies. In this study we have focused on formulation of tissue scaffolds comprised of mesenchymal stem cells and simvastatin loaded nanostructured lipid carriers (NLCs) dispersed in a polymeric matrix. These three dimensional and biodegradable systems were designed to bring a new perspective in treatment of diabetic wound. Therefore, NLC formulations containing simvastatin at the concentrations of 10% or 20% of lipid phase were prepared by high pressure homogenization technique. Simvastatin loaded NLC formulations were characterized with mean particle size of 158.15 ± 1.229 nm, PDI values lower than 0.17 and encapsulation efficiency above 99%. In-vitro release studies of simvastatin loaded NLC formulations were characterized by a high burst-release followed by sustained up to 12–24 h. Tissue scaffold formulations containing simvastatin loaded NLCs were prepared by freeze drying method. Cross-linked tissue scaffold formulations were prepared with 2:1 chitosan:collagen polymer ratio and 2-fold concentrated NLC formulation, having a three-dimensional structure with porosity value of 74.38%, pore size distribution within 20–200 μm, 710.88% high water absorption capacity, 57.7% weight loss and suitable mechanical strength for in-vivo studies. Incorporation of NLCs into tissue scaffolds decreased the initial simvastatin burst release ratio and provided controlled release profile. Tissue scaffolds containing simvastatin lipid nanoparticles increased wound closure rate, promoted vascularization of injured tissue and enhanced viability and proliferation of stem cells. Thereupon, tissue scaffold formulation containing simvastatin lipid nanoparticles and stem cells together provided effective wound healing with increased epithelialization, proliferation and vascularization.

Oatmeal induced gut microbiota alteration and its relationship with improved lipid profiles: a secondary analysis of a randomized clinical trial

BackgroundIn vitro and animal experiments reported a microbiota-regulating ability of oatmeal, however, related in vivo evidences remained limited. Thus, we conducted this study aiming to investigate the oatmeal-induced alteration of gut microbiota and its potential relationship with the improvements of lipid profiles.Methods and study designData of anthropometric measurements and biochemical parameters were extracted from a randomized, controlled clinical trial, in which 62 hypercholesterolemic men and women (18–65 years old) were provided with either treatment of 80 g/day oatmeal or 80 g/day refined white rice for 45 days. Fasting blood samples and fecal samples were collected both at baseline and endpoint of the study for lipid profiling and microbiota 16S rRNA amplicon sequencing, respectively.ResultsTotally 28 participants (56 fecal samples) qualified with the new criteria and were thus included in this secondary analysis. The results of microbiota analysis showed that no significant difference was observed in the alteration of its overall α or β diversity between two groups throughout the study. Nor did any notable between-group difference was found in the relative abundance changes of microorganism at different taxonomies. However, results from linear discriminant analysis effect size in the oatmeal group indicated a significant positive response of Firmicutes phylum following oatmeal consumption. Further Procrustes analysis suggested a concordance trend between microorganism alteration and alleviation of hypercholesterolemia phenotypes throughout the study (P = 0.05). The results of within-group comparison from Spearman’s correlation in the oatmeal group demonstrated a significant association between the enrichment of Blautia genus and the reduction of serum total cholesterol (P < 0.05), low-density lipoprotein cholesterol (P < 0.01), and apolipoprotein B (P < 0.05).ConclusionsPositive response of Firmicutes phylum might be a critical characteristic of oatmeal-induced alteration of microbiota, whereas, one of the underlying cholesterol-lowering mechanism of oatmeal consumption might be its microbiota-manipulating ability, in which the enrichment of Blautia genus played a potentially significant role. Current results should be taken cautiously and more studies were needed for further verification.Trial registration: ChiCTR, ChiCTR180001864. Registered 30 September 2018, http://www.chictr.org.cn/showproj.aspx?proj=31469.

Interactions of bile salts with a dietary fibre, methylcellulose, and impact on lipolysis

Methylcellulose (MC) has a demonstrated capacity to reduce fat absorption, hypothetically through bile salt (BS) activity inhibition. We investigated MC cholesterol-lowering mechanism, and compared the influence of two BS, sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), which differ slightly by their architecture and exhibit contrasting functions during lipolysis.BS/MC bulk interactions were investigated by rheology, and BS behaviour at the MC/water interface studied with surface pressure and ellipsometry measurements. In vitro lipolysis studies were performed to evaluate the effect of BS on MC-stabilised emulsion droplets microstructure, with confocal microscopy, and free fatty acids release, with the pH-stat method.Our results demonstrate that BS structure dictates their interactions with MC, which, in turn, impact lipolysis. Compared to NaTC, NaTDC alters MC viscoelasticity more significantly, which may correlate with its weaker ability to promote lipolysis, and desorbs from the interface at lower concentrations, which may explain its higher propensity to destabilise emulsions.

Screening for Cholesterol-Lowering Probiotics from Lactic Acid Bacteria Isolated from Corn Silage Based on Three Hypothesized Pathways.

A total of 85 strains of lactic acid bacteria were isolated from corn silage in this study and analyzed in vitro for their cholesterol removal, NPC1L1 protein down-regulation and bile salt deconjugation ability, respectively. Nineteen strains were selected for further analysis for their probiotic potential. Finally, 3 strains showing better probiotic potential were evaluated for their cholesterol-lowering activity in hamsters. The strains showing the greater cholesterol removal and NPC1L1 protein down-regulation activity had no significant effects on serum and hepatic cholesterol levels in hamsters (p > 0.05). However, Lactobacillus plantarum CAAS 18008 (1 × 109 CFU/d) showing the greater bile salt deconjugation ability significantly reduced serum low-density lipoprotein cholesterol, total cholesterol, and hepatic total cholesterol levels by 28.8%, 21.7%, and 30.9%, respectively (p < 0.05). The cholesterol-lowering mechanism was attributed to its bile salt hydrolase activity, which enhanced daily fecal bile acid excretion levels and thereby accelerated new bile acid synthesis from cholesterol in liver. This study demonstrated that the strains showing greater cholesterol removal and NPC1L1 protein down-regulation activity in vitro hardly reveal cholesterol-lowering activity in vivo, whereas the strains showing greater bile salt deconjugation ability in vitro has large potential to decrease serum cholesterol levels in vivo.

Cholesterol-lowering potentials of Lactobacillus strain overexpression of bile salt hydrolase on high cholesterol diet-induced hypercholesterolemic mice.

Hypercholesterolemia is closely associated with cardiovascular disease. Supplementation with probiotics has been shown to contribute to improving lipid metabolism. The probiotic mechanisms of cholesterol reduction are complicated and remain unclear. One of the potential probiotic mechanisms for cholesterol reduction is the deconjugation of bile salts. We previously found a high bile salt hydrolase (BSH) activity of Lactobacillus casei pWQH01 (overexpression of bsh1) and Lactobacillus plantarum AR113, but found no BSH activity for Lactobacillus casei LC2W in vitro. Therefore, we decided to investigate whether the high BSH activity of L. plantarum AR113 and L. casei pWQH01 could exert a cholesterol-reducing effect in vivo. Compared to the high-cholesterol diet (HCD) group, AR113 and pWQH01 groups had a significantly lower body weight (BW), serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels and atherogenic index (AI), whereas the LC2W group had a poor capability to mitigate the blood lipid levels in the hypercholesterolemic mice. In addition, the AR113 and pWQH01 groups decreased the hepatic levels of TC and LDL-C and improved hepatic steatosis compared with the HCD group. To explore their cholesterol-lowering mechanisms of action, we determined the expression levels of these genes on the cholesterol metabolic pathways. AR113 and pWQH01 groups downregulated the expression of farnesoid X receptor (FXR) and small heterodimer partner (SHP) genes, but upregulated the expression of the cholesterol 7α-hydroxylase (CYP7A1) gene in the liver. Simultaneously, the expression of cholesterol liver X receptor (LXR) and low density lipoprotein receptor (LDLR) genes was upregulated in the liver. These results indicated that L. plantarum AR113 and L. casei pWQH01 could inhibit the cholesterol absorption and accelerate the cholesterol transportation. Taken together, these findings suggest that Lactobacillus strain overexpression of bile salt hydrolase has beneficial effects against hypercholesterolemia by reducing cholesterol absorption and increasing cholesterol catabolism.

Lipid profile improvement of food products containing bioactive compounds from unsaponifiable matters of palm fatty acid distillate in hypercholesterolemia rats

BACKGROUND: Unsaponifiable matters (USM) from palm fatty acid distillate (PFAD) contains vitamin E (mainly tocotrienols), phytosterols, and squalene that have ability to reduce blood cholesterol. Fortification of USM into food products is a way for hypercholesterolemia management. OBJECTIVE: This study evaluated effects of fortification of USM from PFAD into instant noodle, bread, and biscuit on lipid profile improvement of hypercholesterolemia rats. It was also aimed to compare the effects of different type of foods as USM carrier that represented different processing steps and nutritional composition. METHODS: Rats were divided into control-standard diet and atherogenic diet fed groups, and 6 hypercholesterolemia groups fed by instant noodle, plain bread, and biscuit with 1% USM fortification and without fortification for 8 weeks. Lipid profile (total cholesterol, triglyceride, LDL cholesterol, and HDL cholesterol) was analysed at week 0, 4, and 8. Hepatic and fecal cholesterol and bile acid were also examined at the end of experiment to elucidate some mechanism of cholesterol lowering due to USM fortified foods administration. RESULTS: Some bioactive compounds lost during USM fortified food preparation and the highest retention was found in biscuit. Lipid profile improvement was indicated by reduction of total cholesterol, triglyceride, and LDL cholesterol, meanwhile HDL cholesterol increased. Type of fortified foods affected the level of alteration of lipid profile. Degree of lipid profile improvement was affected by nutritional composition of fortified foods, food intake of the rats, and level of bioactive content. Bioactive compounds in USM fortified foods inhibited cholesterol absorption that indicated by higher fecal cholesterol and bile acid compared to atherogenic diet fed group. Modulation of cholesterol synthesis was likely to occur that indicated by lower hepatic cholesterol and higher bile acids. CONCLUSIONS: Feeding of USM fortified food products improved lipid profile of hypercholesterolemia rats.