Microbial Fermentation Enhances the Effect of Black Tea on Hyperlipidemia by Mediating Bile Acid Metabolism and Remodeling Intestinal Microbes.

Black tea (BT), the most consumed tea worldwide, can alleviate hyperlipidemia which is a serious threat to human health. However, the quality of summer BT is poor. It was improved by microbial fermentation in a previous study, but whether it affects hypolipidemic activity is unknown. Therefore, we compared the hypolipidemic activity of BT and microbially fermented black tea (EFT). The results demonstrated that BT inhibited weight gain and improved lipid and total bile acid (TBA) levels, and microbial fermentation reinforced this activity. Mechanistically, both BT and EFT mediate bile acid circulation to relieve hyperlipidemia. In addition, BT and EFT improve dyslipidemia by modifying the gut microbiota. Specifically, the increase in Lactobacillus johnsonii by BT, and the increase in Mucispirillum and Colidextribacter by EFT may also be potential causes for alleviation of hyperlipidemia. In summary, we demonstrated that microbial fermentation strengthened the hypolipidemic activity of BT and increased the added value of BT.

Control de la hipercolesterolemia en España: una misma situación con diferentes realidades autonómicas / Hypercholesterolaemia control in Spain: The same situation with different regional realities

Introducción y objetivos: La estrategia de prevención cardiovascular en las comunidades autónomas (CCAA) puede ser variable, al estar transferidas las competencias en sanidad. El objetivo del estudio fue conocer el control de la dislipemia y la terapia hipolipemiante utilizada en pacientes de alto/muy alto riesgo cardiovascular (RCV) por CCAA. Métodos: Estudio descriptivo, transversal, multicéntrico no aleatorizado basado en una metodología de consenso. Se recogió información de práctica clínica en 145 áreas sanitarias de 17CCAA españolas mediante reuniones presenciales y cuestionarios realizados a los 435 médicos participantes. Se recopilaron datos agregados no identificables de 10 pacientes dislipémicos consecutivos que cada participante hubiera visitado recientemente. Resultados: De los 4.010 pacientes compilados, 649 (16%) eran de alto y 2.458 (61%) de muy alto RCV. La distribución de los 3.107 pacientes de alto/muy alto RCV fue equilibrada entre regiones, pero hubo diferencias interterritoriales (p<0,0001) en la consecución del objetivo de cLDL<70 e <55mg/dl, respectivamente. Las estatinas de alta intensidad en monoterapia o combinadas con ezetimiba y/o inhibidores PCSK9 se utilizaron en el 44, el 21 y el 4% de los pacientes de alto RCV, mientras que en los de muy alto RCV era del 38, del 45 y del 6%, respectivamente. El uso de estas terapias hipolipemiantes a nivel nacional fue significativamente diferente entre regiones (p=0,0079). Conclusiones: A pesar de que la distribución de los pacientes de alto/muy alto RCV fue similar entre CCAA, se identificaron diferencias interterritoriales en el grado de consecución del objetivo terapéutico en cLDL y de utilización de la terapia hipolipemiante. (AU)

Introduction and objective: The cardiovascular prevention strategy by autonomous communities can be variable since the competences in health are transferred. The objective of the study was to determine the degree of dyslipidaemia control and the lipid-lowering pharmacological therapy used in patients at high/very high cardiovascular risk (CVR) by autonomous communities. Methods: Observational, cross-sectional, descriptive study based on a consensus methodology. Information on the clinical practice of 145 health areas belonging to 17 Spanish autonomous communities was collected through face-to-face meetings and questionnaires administered to the 435 participating physicians. Furthermore, aggregate non-identifiable data were compiled from 10 consecutive dyslipidaemic patients that each participant had recently visited. Results: Of the 4010 patients collected, 649 (16%) had high and 2458 (61%) very high CVR. The distribution of the 3107 high/very high CVR patients was balanced across regions, but there were inter-regional differences (P<.0001) in the achievement of target LDL-C <70 and <55mg/dL, respectively. High-intensity statins in monotherapy or in combination with ezetimibe and/or PCSK9 inhibitors were used in 44, 21 and 4% of high CVR patients, while in those at very high CVR it rose to 38, 45 and 6%, respectively. The use of these lipid-lowering therapies at national level was significantly different between regions (P=.0079). Conclusions: Even though the distribution of patients at high/very high CVR was similar between autonomous communities, inter-territorial differences were identified in the degree of achievement of LDL cholesterol therapeutic goal and use of lipid-lowering therapy. (AU)

Rice Bran Extract Suppresses High-Fat Diet-Induced Hyperlipidemia and Hepatosteatosis through Targeting AMPK and STAT3 Signaling.

Rice bran, a by-product of rice milling, is abundant in bioactive molecules and is highly recognized for its health-promoting properties, particularly in improving metabolic conditions. Building on this knowledge, we aimed to optimize the extraction conditions to maximize the functional efficacy of rice bran extract (RBE) and further validate its impact on lipid metabolism. We found that the optimized RBE (ORBE) significantly suppressed high-fat diet-induced weight gain, hyperlipidemia, and hepatosteatosis in mouse models. ORBE treatment not only suppressed lipid uptake in vivo, but also reduced lipid accumulation in HepG2 cells. Importantly, we discovered that ORBE administration resulted in activation of AMPK and inhibition of STAT3, which are both crucial players in lipid metabolism in the liver. Collectively, ORBE potentially offers promise as a dietary intervention strategy against hyperlipidemia and hepatosteatosis. This study underlines the value of optimized extraction conditions in enhancing the functional efficacy of rice bran.

Polyphenol-rich extract from loquat fruit peel prevents hyperlipidemia and hepato-nephrotoxicity in mice: in vivo study and in silico prediction of possible mechanisms involving identified polyphenols and/or their circulating metabolites.

Hyperlipidemia is the most well-known cause of metabolic complications and tissue toxicity such as liver steatosis, atherosclerosis and obesity. This study aims to evaluate the preventive effect of loquat fruit peel extract (PE) against tyloxapol-induced hyperlipidemia and related tissue lipotoxicity in mice. The in vivo study was conducted on mice injected daily with tyloxapol at 100 mg per kg B.W. and treated simultaneously with the PE at concentrations of 100 and 200 mg kg-1 or fenofibrate for 28 days. Plasma and tissue lipid biochemical analyses were undertaken using enzymatic methods. The antioxidative stress was revealed by measuring the malondialdehyde content and activities of superoxide dismutase and catalase as well as the scavenging activity against lipoperoxyl radicals. The PE significantly prevented oxidative stress and restored lipid metabolism, plasma glucose, body weight, organ relative mass and biomarkers of hepato-nephrotoxicity as well as the histological structure of the liver and kidneys. It contains five major polyphenols, namely, ferulic acid, caffeic acid, neochlorogenic acid, chlorogenic acid and quercetin. According to molecular docking analysis, these compounds and their circulating metabolites could interact with major proteins implicated in lipid metabolism and oxidative stress. Overall, the study suggests that PE could prevent hyperlipidemia and related toxic tissue complications.

Blood Microbiota Profile Is Associated with the Responsiveness of Postprandial Lipemia to Platycodi radix Beverage: A Randomized Controlled Trial in Healthy Subjects.

Prolonged postprandial hyperlipidemia may cause the development of cardiovascular diseases. This study explored whether postprandial triglyceride-rich lipoprotein (TRL) clearance responsiveness to Platycodi radix beverage (PR) is associated with changes in blood microbiota profiles. We conducted an 8-week randomized controlled clinical trial involving normolipidemic adults with low fruit and vegetable intakes. Participants underwent an oral fat tolerance test and 16S amplicon sequencing analysis of blood microbiota. Using the Qualitative Interaction Trees, we identified responders as those with higher baseline dietary fat intake (>38.5 g/day) and lipoprotein lipase levels (>150.6 ng/mL), who showed significant reductions in AUC for triglyceride (TG) and chylomicron-TG after the oral fat tolerance test. The LEfSe analysis showed differentially abundant blood microbiota between responders and non-responders. A penalized logistic regression algorithm was employed to predict the responsiveness to intervention on the TRL clearance based on the background characteristics, including the blood microbiome. Our findings suggest that PR intake can modulate postprandial TRL clearance in adults consuming higher fat intake over 38.5 g/day and low fruit and vegetable intake through shared links to systemic microbial signatures.

Black rice regulates lipid metabolism, liver injury, oxidative stress and adipose accumulation in high-fat/cholesterol diet mice based on gut microbiota and untargeted metabonomics.

Black rice displays a series of properties including regulating lipid metabolism and attenuating liver injury. Our study aimed to investigate the effect of Zixiangnuo black rice (ZG), peeled rice (ZPG), rice bran (ZBG) on lipid metabolism, liver inflammation, gut microbiota and metabolite profiles in high-fat/cholesterol (HFCD) diet mice. A total of five treatment groups were fed a normal control diet or a HFCD with or without Highland barley (HB) supplementation for 10 weeks. The results showed that ZBG significantly improved lipid parameters, liver function and injury and blood glucose indexes related to hyperlipidemia compared with HFCD group. ZBG recovered the disorder of gut microbiota by increasing Bacteroidetes/Firmicutes ratio and Lactobacillus abundance, and decreasing Proteobacteria abundance. ZBG enhanced the levels of six short chain fatty acids. Fecal metabolomics analysis showed that the important differential metabolites between ZBG and HFCD group were Deoxycholic acid and Myclobutanil, and metabolic pathways were Arachidonic acid metabolism and ABC transporters. Results suggested that BR or bran were effective dietary candidates to ameliorate hyperlipidemia.

Multiple time-dependent pathophysiological changes in a rabbit model of high-fat diet-induced hyperlipidemia.

High-fat diets (HFD) adversely affect organ systems. Several studies have examined HFD-related disorders in animals but only in a few organs and time points. Herein, we evaluated disease development with time-dependent HFD-induced pathological, cardiovascular, and morphological changes in rabbits with lipid metabolism similar to that in humans for 9 weeks. The body weights and waist ratio of the HFD group were higher than those in the control group. HFD significantly increased the total cholesterol, low-density lipoprotein, high-density lipoprotein, and phospholipid levels after 3 weeks. Liver enzyme levels increased with hepatomegaly, steatosis, and fibrosis after 3 or 6 weeks. RBCs and hemoglobin decreased, while platelets increased in the HFD group with atherosclerosis and inflammatory cell infiltration in the aorta after 6 weeks. Ejection fraction and fractional shortening values decreased in the HFD group after 9 weeks. Creatinine increased with glomerulosclerosis in the kidneys of the HFD groups after 3 weeks, indicating renal dysfunction. Lipid accumulation was found in the pancreas after 9 weeks. Lipid accumulation and hypertrophy were observed in the adrenal glands after 3 weeks. Overall, our findings provide global reference data on the time-dependent effects of HFD on the body and may serve as a guide for future HFD risk prevention.

Probiotic-fermented blueberry pomace alleviates obesity and hyperlipidemia in high-fat diet C57BL/6J mice.

This study investigated the effect of FBP (fermented blueberry pomace by the mixture of Lactobacillus rhamnosus GG and Lactobacillus plantarum-1) on hyperlipidemia in high-fat diet (HFD)-induced C57BL/6J obese mice. The results indicated that FBP significantly reduced the weight gain, liver and fat indexes, and hyperlipidemia of HFD mice. Serum TC, TG, and LDL-C in HFD mice were significantly decreased through supplementation with FBP, and serum SOD, GSH-Px, CAT, and T-AOC in H-FBP group were increased by 28.25%, 26.84%, 23.30%, and 19.79%, respectively. Furthermore, FBP reduced the activity of ALT, AST, and LPS; down-regulated the expression of inflammation-related cytokines (TNF-α, IL-1ß, and IL-6); and improved lipid metabolism by up-regulating PPAR-α and down-regulating SREBP-1 and FAS. Thus, FBP alleviated obesity, liver injury, and inflammation caused by a HFD by increasing antioxidant capacity and reducing leptin production, indicating that FBP is a nutrient-rich beverage with the potential to relieve obesity. Generally, this study highlightsed a new use of blueberry pomace.

Exercise to Lower Postprandial Lipemia: Why, When, What and How.

We review recent findings on the ability of exercise to lower postprandial lipemia (PPL). Specifically, we answer why exercise is important in lowering PPL, when it is most effective to exercise to achieve this, what the preferred exercise is and how exercise reduces PPL. Most findings confirm the power of exercise to lower PPL, which is an independent risk factor for cardiovascular disease. Exercise is most effective when performed on the day preceding a high- or moderate-fat meal. This effect lasts up to approximately two days; therefore, one should exercise frequently to maintain this benefit. However, the time of exercise relative to a meal is not that important in real-life conditions, since one consumes several meals during the day; thus, an exercise bout will inevitably exert its lowering effect on PPL in one or more of the subsequent meals. Although moderate-intensity continuous exercise, high-intensity intermittent exercise, resistance exercise and accumulation of short bouts of exercise throughout the day are all effective in lowering PPL, submaximal, high-volume interval exercise seems to be superior, provided it is tolerable. Finally, exercise reduces PPL by both lowering the rate of appearance and increasing the clearance of triacylglycerol-rich lipoproteins from the circulation.

Prior arm-crank exercise has no effect on postprandial lipaemia in nondisabled adults.

A single bout of cycling or running performed in the evening can reduce postprandial lipaemia (PPL) the following morning, although this is currently unknown for upper-body exercise. The aim of this study was to determine if a bout of arm-crank exercise (high-intensity interval [HIIE] or moderate-intensity continuous [MICE]), can attenuate PPL in noninjured individuals. Eleven healthy and recreationally active participants (eight males, three females; age: 27 ± 7 years; body mass index: 23.5 ± 2.5 kg·m-2) volunteered to participate in three trials: HIIE (10 × 60 s at 80% peak power output), MICE (50% peak power output of isocaloric duration), and a no-exercise control condition. Each exercise bout was performed at 18:00, and participants consumed a standardised evening meal at 20:00. Following an overnight fast, a 5-h mixed-macronutrient tolerance test was performed at 08:00. There were no significant differences in triglyceride incremental area under the curve between HIIE (192 ± 94 mmol·L-1 per 300 min), MICE (184 ± 111 mmol·L-1 per 300 min), and the no-exercise condition (175 ± 90 mmol·L-1 per 300 min) (P = 0.46). There were no significant differences in incremental area under the curve for glucose (P = 0.91) or insulin (P = 0.59) between conditions. Upper-body MICE and HIIE performed in the evening do not influence PPL the following morning, in normotriglyceridemic individuals. Clinical Trials Registration: NCT04277091. Novelty: Arm-crank exercise has no effect on PPL when performed the evening prior to a mixed-macronutrient meal test. Upper-body sprint interval exercise should be investigated as a potential solution to reduce PPL.

Nobiletin Prevents High-Fat Diet-Induced Dysregulation of Intestinal Lipid Metabolism and Attenuates Postprandial Lipemia.

OBJECTIVE: Nobiletin is a dietary flavonoid that improves insulin resistance and atherosclerosis in mice with metabolic dysfunction. Dysregulation of intestinal lipoprotein metabolism contributes to atherogenesis. The objective of the study was to determine if nobiletin targets the intestine to improve metabolic dysregulation in both male and female mice. Approach and Results: Triglyceride-rich lipoprotein (TRL) secretion, intracellular triglyceride kinetics, and intestinal morphology were determined in male and female LDL (low-density lipoprotein) receptor knockout (Ldlr-/-), and male wild-type mice fed a standard laboratory diet or high-fat, high-cholesterol (HFHC) diet ± nobiletin using an olive oil gavage, radiotracers, and electron microscopy. Nobiletin attenuated postprandial TRL levels in plasma and enhanced TRL clearance. Nobiletin reduced fasting jejunal triglyceride accumulation through accelerated TRL secretion and lower jejunal fatty acid synthesis with no impact on fatty acid oxidation. Fasting-refeeding experiments revealed that nobiletin led to higher levels of phosphorylated AKT (protein kinase B) and FoxO1 (forkhead box O1) and normal Srebf1c expression indicating increased insulin sensitivity. Intestinal length and weight were diminished by HFHC feeding and restored by nobiletin. Both fasting and postprandial plasma GLP-1 (glucagon-like peptide-1; and likely GLP-2) were elevated in response to nobiletin. Treatment with a GLP-2 receptor antagonist, GLP-2(3-33), reduced villus length in HFHC-fed mice but did not impact TRL secretion in any diet group. In contrast to males, nobiletin did not improve postprandial lipid parameters in female mice. CONCLUSIONS: Nobiletin opposed the effects of the HFHC diet by normalizing intestinal de novo lipogenesis through improved insulin sensitivity. Nobiletin prevents postprandial lipemia because the enhanced TRL clearance more than compensates for increased TRL secretion.

Deficiency of inactive rhomboid protein 2 (iRhom2) attenuates diet-induced hyperlipidaemia and early atherogenesis.

AIMS: Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall and anti-inflammatory treatment strategies are currently pursued to lower cardiovascular disease burden. Modulation of recently discovered inactive rhomboid protein 2 (iRhom2) attenuates shedding of tumour necrosis factor-alpha (TNF-α) selectively from immune cells. The present study aims at investigating the impact of iRhom2 deficiency on the development of atherosclerosis. METHODS AND RESULTS: Low-density lipoprotein receptor (LDLR)-deficient mice with additional deficiency of iRhom2 (LDLR-/-iRhom2-/-) and control (LDLR-/-) mice were fed a Western-type diet (WD) for 8 or 20 weeks to induce early or advanced atherosclerosis. Deficiency of iRhom2 resulted in a significant decrease in the size of early atherosclerotic plaques as determined in aortic root cross-sections. LDLR-/-iRhom2-/- mice exhibited significantly lower serum levels of TNF-α and lower circulating and hepatic levels of cholesterol and triglycerides compared to LDLR-/- mice at 8 weeks of WD. Analyses of hepatic bile acid concentration and gene expression at 8 weeks of WD revealed that iRhom2 deficiency prevented WD-induced repression of hepatic bile acid synthesis in LDLR-/- mice. In contrast, at 20 weeks of WD, plaque size, plaque composition, and serum levels of TNF-α or cholesterol were not different between genotypes. CONCLUSION: Modulation of inflammation by iRhom2 deficiency attenuated diet-induced hyperlipidaemia and early atherogenesis in LDLR-/- mice. iRhom2 deficiency did not affect diet-induced plaque burden and composition in advanced atherosclerosis in LDLR-/- mice.

The Association between Treatment Modality, Lipid Profile, Metabolic Control in Children with Type 1 Diabetes and Celiac Disease-Data from the International Sweet Registry.

BACKGROUND AND AIMS: A higher frequency of dyslipidemia is reported in children with type 1 diabetes (T1D) and celiac disease (CD). Recently, continuous subcutaneous insulin infusion (CSII) has been associated with better lipid profiles in patients with T1D. The aim of this study was to investigate the association between treatment modality and lipid profile, metabolic control, and body mass index (BMI)-SDS in children with both T1D and CD. METHODS: Cross-sectional study in children registered in the international SWEET database in November 2020. Inclusion criteria were children (2-18 years) with T1D and CD with available data on treatment modality (CSII and injections therapy, IT), triglyceride, total cholesterol, HDL, LDL, dyslipidemia, HbA1c, and BMI-SDS. Overweight/obesity was defined as > +1 BMI-SDS for age. Data were analyzed by linear and logistical regression models with adjustment for age, gender, and diabetes duration. RESULTS: In total 1009 children with T1D and CD (female 54%, CSII 54%, age 13.9 years ±3.6, diabetes duration 7.2 years ±4.1, HbA1c 7.9% ±1.4) were included. Significant differences between children treated with CSII vs. IT were respectively found; HDL 60.0 mg/dL vs. 57.8 mg/dL, LDL 89.4 mg/dL vs. 94.2 mg/dL, HbA1c 7.7 vs. 8.1%, BMI-SDS 0.4 vs. 0.6, overweight and obesity 17% vs. 26% (all p < 0.05). CONCLUSIONS: CSII is associated with higher HDL and lower LDL, HbA1c, BMI-SDS, and percentage of overweight and obesity compared with IT in this study. Further prospective studies are required to determine whether CSII improves lipid profile, metabolic control and normalize body weight in children with both T1D and CD.

Total Sesquiterpene Glycosides from Loquat Leaves Ameliorate HFD-Induced Insulin Resistance by Modulating IRS-1/GLUT4, TRPV1, and SIRT6/Nrf2 Signaling Pathways.

Loquat (Eriobotrya japonica Lindl.), a subtropical fruit tree native to Asia, is not only known to be nutritive but also beneficial for the treatment of diabetes in the south of China. To expand its development, this study was undertaken concerning the potential therapeutic role of total sesquiterpene glycosides (TSGs) from loquat leaves in insulin resistance (IR), the major causative factor of type 2 diabetes mellitus (T2DM). Male C57BL/6 mice were fed on high-fat diet (HFD) to induce IR and then were given TSG by oral administration at 25 and 100 mg/kg/day, respectively. TSG notably improved metabolic parameters including body weight, serum glucose, and insulin levels and prevented hepatic injury. Moreover, inflammatory response and oxidative stress were found to be remarkably alleviated in IR mice with TSG supplement. Further research in liver of IR mice demonstrated that TSG repaired the signalings of insulin receptor substrate-1 (IRS-1)/glucose transporter member 4 (GLUT4) and AMP-activated protein kinase (AMPK), which improved glucose and lipid metabolism and prevented lipid accumulation in liver. It was also observed that TSG suppressed the expression of transient receptor potential vanilloid 1 (TRPV1), whereas the signaling pathway of sirtuin-6 (SIRT6)/nuclear factor erythroid 2-related factor 2 (Nrf2) was significantly promoted. Based on the results, the current study demonstrated that TSG from loquat leaves potentially ameliorated IR in vivo by enhancing IRS-1/GLUT4 signaling and AMPK activation and modulating TRPV1 and SIRT6/Nrf2 signaling pathways.

Functional Profiling and Future Research Direction of Rice Bran Oil in Bangladesh.

Rice bran oil (RBO) has been demonstrated to affect complex malfunctioned conditions such as oxidative stress, hyperlipidemia, hyperglycemia, hypertension, inflammation, abnormal cell growth (cancer), ulceration, immune and cognitive modulation. This unique effect of RBO is due to the presence of well-balanced fatty acid composition and several bioactive compounds, γ- oryzanol (cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, campesterol ferulate, and ß-sitosteryl ferulate), vitamin E (tocopherol and tocotrienol), phytosterols (ß-sitosterol, campesterol and stigmasterol) and other nutrients. The RBO composition of bioactive compounds varied geographically, thus the clear-cut mechanisms of action on complex disease cascades are still required. This review article summarized the RBO compositional profiling and compared it with other edible oils. This article also summarized Bangladesh RBO profiling and their proposed mechanism of action as well as the first line of defense in the prevention, management, and control of complex disease conditions. This review indicates how Bangladesh RBO increase their opportunity to be functional food for 21st century's ailment.

Engineered red blood cells carrying PCSK9 inhibitors persistently lower LDL and prevent obesity.

Low plasma levels of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) are associated with decreased low-density lipoprotein (LDL) cholesterol and a reduced risk of cardiovascular disease. PCSK9 binds to the epidermal growth factor-like repeat A (EGFA) domain of LDL receptors (LDLR), very low-density lipoprotein receptors (VLDLR), apolipoprotein E receptor 2 (ApoER2), and lipoprotein receptor-related protein 1 (LRP1) and accelerates their degradation, thus acting as a key regulator of lipid metabolism. Antibody and RNAi-based PCSK9 inhibitor treatments lower cholesterol and prevent cardiovascular incidents in patients, but their high-cost hampers market penetration. We sought to develop a safe, long-term and one-time solution to treat hyperlipidemia. We created a cDNA encoding a chimeric protein in which the extracellular N- terminus of red blood cells (RBCs) specific glycophorin A was fused to the LDLR EGFA domain and introduced this gene into mouse bone marrow hematopoietic stem and progenitor cells (HSPCs). Following transplantation into irradiated mice, the animals produced RBCs with the EGFA domain (EGFA-GPA RBCs) displayed on their surface. These animals showed significantly reduced plasma PCSK9 (66.5% decrease) and reduced LDL levels (40% decrease) for as long as 12 months post-transplantation. Furthermore, the EGFA- GPA mice remained lean for life and maintained normal body weight under a high-fat diet. Hematopoietic stem cell gene therapy can generate red blood cells expressing an EGFA-glycophorin A chimeric protein as a practical and long-term strategy for treating chronic hyperlipidemia and obesity.

Zeolite Improves High-Fat Diet-Induced Hyperglycemia, Hyperlipidemia and Obesity in Mice.

Zeolite, an abundant mineral in the Earth's crust, is utilized in a wide range of fields because of its well-known adsorption properties. Its application as a functional food ingredient resembling dietary fiber is expected, but it has not yet been investigated in the context of prevention of lifestyle-related diseases. The present study was designed to evaluate the availability and safety of a natural zeolite preparation for this purpose. Acute oral toxicity testing showed that the lowest lethal dose of zeolite was more than 2,000 mg/kg body weight for both male and female mice. In a prolonged feeding test for 18 wk using model mice with high-fat-induced obesity and type 2 diabetes mellitus, intake of a 10% zeolite-containing diet suppressed body weight gain, as well as liver and visceral fat weights, without any changes in food and energy intake. Moreover, plasma lipid (triacylglycerol, total cholesterol and high-density-lipoprotein cholesterol) levels and fasting blood glucose levels decreased in parallel with zeolite intake. No changes in the glycated hemoglobin level were found. However, in an oral glucose tolerance test at week 12, increased postprandial blood glucose levels were suppressed in accordance with zeolite intake, and then insulin secretion was also decreased. On the other hand, a decrease of plasma amylase activity and increases in total bilirubin and urea nitrogen suggested the need for further investigation of safety.

Preventive role of propolis against hyperglycemia and hyperlipidemia in Sprague dawley rats (Rattus norvegicus) animal modelling system.

Human diets with functional ingredients showed promising role in management of diseases of modern age like hyperglycemia and hyperlipidemia and even cancer. The study designed to elucidate role of honeybee propolis for management of hyperglycemia and hyperlipidemia states through animal modeling system. Hydroalcoholic extract of propolis was used for development of functional drink with standard recipe and addition of specified dose of extracts (400mg/500mL). Animals were grouped into three studies including study-I fed on regular diet, study-II fed on sucrose enrich diet and study-III fed on diet enriched with cholesterol and monitored to evaluate the results. Various parameters like feed consumption, liquid intake of animals measured regularly whereas body weight recorded at the end of each week of study. At the end of the study animals were analyzed for different blood indicators like blood lipid indices (cholesterol, LDL, HDL concentration and triglyceride contents)), glucose concentration and insulin contents as well. The maximum feed and drink intake were examined in animals, fed with control diet whereas a non substantial mode of intake was recorded in rest of two groups of animals. The consumption of honeybee propolis based drink reduced cholesterol (6.63% to 10.25%) and LDL (9.96% to 11.23%), whilst a sharp increase in HDL level was ranged as 4.12 to 4.49% among animal groups fed with high cholesterol and high sucrose diet. Blood glucose level was decreased by 10.25% and 6.98% however 6.99% and 4.51% increase were observed in plasma insulin level in both studies, study-II and study-III correspondingly. The overall findings of the study showed that drinks prepared using propolis of propolis found effective for management of hyperglycemia and hypercholesterolemia in present animal modelling system.

Rosmarinic Acid Exhibits a Lipid-Lowering Effect by Modulating the Expression of Reverse Cholesterol Transporters and Lipid Metabolism in High-Fat Diet-Fed Mice.

Hyperlipidemia is a potent risk factor for the development of cardiovascular diseases. The reverse cholesterol transport (RCT) process has been shown to alleviate hyperlipidemia and protect against cardiovascular diseases. Recently, rosmarinic acid was reported to exhibit lipid-lowering effects. However, the underlying mechanism is still unclear. This study aims to investigate whether rosmarinic acid lowers lipids by modulating the RCT process in high-fat diet (HFD)-induced hyperlipidemic C57BL/6J mice. Our results indicated that rosmarinic acid treatment significantly decreased body weight, blood glucose, and plasma total cholesterol and triglyceride levels in HFD-fed mice. Rosmarinic acid increased the expression levels of cholesterol uptake-associated receptors in liver tissues, including scavenger receptor B type 1 (SR-B1) and low-density lipoprotein receptor (LDL-R). Furthermore, rosmarinic acid treatment notably increased the expression of cholesterol excretion molecules, ATP-binding cassette G5 (ABCG5) and G8 (ABCG8) transporters, and cholesterol 7 alpha-hydroxylase A1 (CYP7A1) as well as markedly reduced cholesterol and triglyceride levels in liver tissues. In addition, rosmarinic acid facilitated fatty acid oxidation through AMP-activated protein kinase (AMPK)-mediated carnitine palmitoyltransferase 1A (CPT1A) induction. In conclusion, rosmarinic acid exhibited a lipid-lowering effect by modulating the expression of RCT-related proteins and lipid metabolism-associated molecules, confirming its potential for the prevention or treatment of hyperlipidemia-derived diseases.

Deficiency of intestinal Bmal1 prevents obesity induced by high-fat feeding.

The role of intestine clock in energy homeostasis remains elusive. Here we show that mice with Bmal1 specifically deleted in the intestine (Bmal1iKO mice) have a normal phenotype on a chow diet. However, on a high-fat diet (HFD), Bmal1iKO mice are protected against development of obesity and related abnormalities such as hyperlipidemia and fatty livers. These metabolic phenotypes are attributed to impaired lipid resynthesis in the intestine and reduced fat secretion. Consistently, wild-type mice fed a HFD during nighttime (with a lower BMAL1 expression) show alleviated obesity compared to mice fed ad libitum. Mechanistic studies uncover that BMAL1 transactivates the Dgat2 gene (encoding the triacylglycerol synthesis enzyme DGAT2) via direct binding to an E-box in the promoter, thereby promoting dietary fat absorption. Supporting these findings, intestinal deficiency of Rev-erbα, a known BMAL1 repressor, enhances dietary fat absorption and exacerbates HFD-induced obesity and comorbidities. Moreover, small-molecule targeting of REV-ERBα/BMAL1 by SR9009 ameliorates HFD-induced obesity in mice. Altogether, intestine clock functions as an accelerator in dietary fat absorption and targeting intestinal BMAL1 may be a promising approach for management of metabolic diseases induced by excess fat intake.