Duyun compound green tea (DCGT) is a healthy beverage with lipid-lowering effect commonly consumed by local people, but its mechanism is not very clear. We evaluated the effect of DCGT treatment on bile acids (BA) metabolism of mice with high-fat diet (HFD) – induced hyperlipidaemia by biochemical indexes and metabolomics and preliminarily determined the potential biomarkers and metabolic pathways of hyperlipidaemia mice treated with DCGT as well as investigated its lipid-lowering mechanism. The results showed that DCGT treatment could reduce HFD – induced gain in weight and improve dyslipidaemia. In addition, a total of ten types of BA were detected, of which seven changed BA metabolites were observed in HFD group mice. After DCGT treatment, glycocholic acid, tauroursodeoxycholic acid and taurochenodeoxycholic acid were significantly down-regulated, while hyodeoxycholic acid, deoxycholic acid and chenodeoxycholic acid were markedly up-regulated. These results demonstrated that DCGT treatment was able to make the BA metabolites in the liver of hyperlipidaemia mice normal and alleviate hyperlipidaemia by regulating the metabolites such as glycocholic acid, tauroursodeoxycholic acid and taurochenodeoxycholic, as well as the BA metabolic pathway and cholesterol metabolic pathway involved.

The association between a dietary pattern characterised by high alcohol intake and dyslipidaemia has not been fully investigated. Therefore, the present study aimed to investigate the association between alcohol dietary patterns and the prevalence of dyslipidaemia and its components. This cross-sectional study enrolled 2171 men and women aged ≥40 years who were alumni of a Japanese university. To identify dietary patterns, a principal component analysis was performed based on the energy-adjusted food intake estimated by a brief-type self-administered diet history questionnaire. Three dietary patterns were identified, the second of which was named the alcohol dietary pattern and was characterised by a high intake of alcoholic beverages, liver, chicken and fish. This alcohol dietary pattern was associated with reduced LDL-cholesterol levels. The fully adjusted OR (95 % CI) of high LDL-cholesterol for the lowest through highest quartile of alcohol dietary pattern score were 1·00 (reference), 0·83 (0·64, 1·08), 0·84 (0·64, 1·10) and 0·68 (0·49, 0·94), respectively. Subgroup analysis showed that the alcohol dietary pattern was inversely associated with the prevalence of dyslipidaemia in women, whereas it was positively associated with high TAG levels in men. In conclusion, the alcohol dietary pattern, characterised by a high intake of alcoholic beverages, liver, chicken and fish, was associated with the prevalence of dyslipidaemia and its components. This finding provides useful information for the prevention and treatment of dyslipidaemia by modifying the diet.

Hyperlipidaemia and cognitive dysfunction (CD) are the two public health concerns. Though hyperlipidaemia has been comprehensively studied in respect to CVD, its role on CD needs to be explored. Hence, we evaluated hyperlipidaemia as a risk factor for CD and the efficacy of EPA (20 : 5n-3) + DHA (22 : 6n-3) and zerumbone (Z) in modulating CD under hyperlipidaemic conditions. Male Wistar rats (Rattus norvegicus) were fed control, high-fat (HF), high-fat + fish oil (HF + F), high-fat + zerumbone (HF+Z) and high-fat + fish oil + zerumbone (HF+F+Z) containing diets. After a 30 d feeding trial, memory parameters (Morris water maze, elevated plus maze (transfer latency) and T-maze (spontaneous alteration)) and locomotor skills (open field test and rotarod test) were assessed. Hyperlipidaemia significantly (P < 0·05) reduced memory and motor coordination skills compared with control. However, the administration of EPA + DHA and zerumbone significantly (P < 0·05) restored the hyperlipidaemia-induced loss of memory and motor coordination skills. Collectively, our data imply that hyperlipidaemia causes CD by decreasing memory and motor coordination skills, and administration of EPA + DHA and zerumbone prevents hyperlipidaemia-induced CD. The augmented effect of EPA + DHA, together with zerumbone, discloses a promising strategy for lowering the severity of CD in hyperlipidaemic conditions.

β-Glucan has been reported for its health benefits on blood lipids in hypercholesterolaemic individuals for years. However, people have paid little attention to the effects of β-glucan in populations with mild hypercholesterolaemia as well as the various delivering matrices. Our objective was to perform a meta-analysis to analyse the effects of β-glucan with different delivering matrices in mildly hypercholesterolaemic individuals. After conducting a comprehensive search in Web of Science, PubMed, Scopus and Cochrane Library, a total of twenty-one randomised controlled trials involving 1120 participants were identified to measure the pooled effect. The overall results indicated that consuming a dose of ≥3 g/d of β-glucan for at least 3 weeks could significantly reduce total cholesterol (TC) (−0·27 mmol/l, 95 % CI −0·33, −0·21, P < 0·001) and LDL-cholesterol (−0·26 mmol/l, 95% CI −0·32, −0·20, P < 0·001) compared with the control group in mildly hypercholesterolaemic individuals, while no significant difference was observed in TAG (−0·03 mmol/l, 95% CI −0·11, 0·06, P = 0·521) and HDL-cholesterol (0·01 mmol/l, 95% CI −0·03, 0·04, P = 0·777). There was evidence for modest unexplained heterogeneity in the meta-analysis. In conclusion, β-glucan can significantly reduce risk factors like TC and LDL-cholesterol for CVD in mildly hypercholesterolaemic individuals; furthermore, it appears that the effects of food matrices with both ‘solid products’ and ‘liquid products’ where β-glucan was incorporated into were ranked as the best way to exert its beneficial properties, while ‘liquid’ and ‘solid’ products were ranked as the second and third positions, respectively.

The in vivo effects of administering free and microencapsulated Lactobacillus plantarum LIP-1 cells (2·0×109 colony-forming units/d) were evaluated in high-fat-diet-induced hyperlipidaemic rats. Results from real-time quantitative PCR targeting to LIP-1 cells showed a higher colon colonisation count of LIP-1 in the rats receiving microencapsulated cells compared with free cells (P<0·05). Moreover, the microencapsulated LIP-1 treatment resulted in a more obvious lipid-lowering effect (P<0·05). Meanwhile, their faecal samples had significantly less lipopolysaccharide-producing bacteria (especially Bilophila, Sutterella and Oscillibacter) and mucosa-damaging bacteria (Bilophila and Akkermansia muciniphila), whereas significantly more SCFA-producing bacteria (P<0·05) (namely Lactobacillus, Alloprevotella, Coprococcus, Eubacterium and Ruminococcus) and bacteria that potentially possessed bile salt hydrolase activity (Bacteroides, Clostridium, Eubacterium and Lactobacillus), and other beneficial bacteria (Alistipes and Turicibacter). Further, Spearman’s correlation analysis showed significant correlations between some of the modulated gut bacteria and the serum lipid levels. These results together confirm that microcapsulation enhanced the colon colonisation of LIP-1 cells, which subsequently exhibited more pronounced effects in improving the gut microbiota composition of hyperlipidaemic rats and lipid reduction.

Hyperlipidaemia is a major cause of atherosclerosis and related CVD and can be prevented with natural substances. Previously, we reported that a novel Bacillus-fermented green tea (FGT) exerts anti-obesity and hypolipidaemic effects. This study further investigated the hypotriglyceridaemic and anti-obesogenic effects of FGT and its underlying mechanisms. FGT effectively inhibited pancreatic lipase activity in vitro (IC50, 0·48 mg/ml) and ameliorated postprandial lipaemia in rats (26 % reduction with 500 mg/kg FGT). In hypertriglyceridaemic hamsters, FGT administration significantly reduced plasma TAG levels. In mice, FGT administration (500 mg/kg) for 2 weeks augmented energy expenditure by 22 % through the induction of plasma serotonin, a neurotransmitter that modulates energy expenditure and mRNA expressions of lipid metabolism genes in peripheral tissues. Analysis of the gut microbiota showed that FGT reduced the proportion of the phylum Firmicutes in hamsters, which could further contribute to its anti-obesity effects. Collectively, these data demonstrate that FGT decreases plasma TAG levels via multiple mechanisms including inhibition of pancreatic lipase, augmentation of energy expenditure, induction of serotonin secretion and alteration of gut microbiota. These results suggest that FGT may be a useful natural agent for preventing hypertriglyceridaemia and obesity.

Obesity and hyperlipidaemia increase the risk of CVD. Some strains of probiotics have been suggested to have potential applications in cardiovascular health by lowering serum LDL-cholesterol. In this work, high-fat diet-induced hyperlipidaemia in hamsters was treated with different doses (5×108 and 2·5×109 cells/kg per d) of heat-killed Lactobacillus reuteri GMNL-263 (Lr263) by oral gavage for 8 weeks. The serum lipid profile analysis showed that LDL-cholesterol and plasma malondialdehyde (P-MDA) were reduced in the GMNL-263 5×108 cells/kg per d treatment group. Total cholesterol and P-MDA were reduced in the GMNL-263 2·5×109 cells/kg per d treatment group. In terms of heart function, the GMNL-263 2·5×109 cells/kg per d treatments improved the ejection fraction from 85·71 to 91·81 % and fractional shortening from 46·93 to 57·92 % in the high-fat diet-fed hamster hearts. Moreover, the GMNL-263-treated, high-fat diet-fed hamster hearts exhibited reduced Fas-induced myocardial apoptosis and a reactivated IGF1R/PI3K/Akt cell survival pathway. Interestingly, the GMNL-263 treatments also enhanced the heat-shock protein 27 expression in a dose-dependent manner, but the mechanism for this increase remains unclear. In conclusion, supplementary heat-killed L. reuteri GMNL-263 can slightly reduce serum cholesterol. The anti-hyperlipidaemia effects of GMNL-263 may reactivate the IGF1R/PI3K/Akt cell survival pathway and reduce Fas-induced myocardial apoptosis in high-fat diet-fed hamster hearts.

Obesity is associated with an increased risk of metabolic abnormalities, such as hyperlipidaemia and hyperglycaemia. We investigated whether polyphenol-rich blackcurrant extract (BCE) can prevent high fat/high cholesterol (HF/HC) diet-induced metabolic disturbances in mice. Male C57BL/6J mice were fed a modified AIN-93M diet containing HF/HC (16 % fat, 0·25 % cholesterol, w/w) or the same diet supplemented with 0·1 % BCE (w/w) for 12 weeks. There were no differences in total body weight and liver weight between groups. Plasma total cholesterol (TC) and glucose levels were significantly lower in BCE group than in controls, while plasma TAG levels were not significantly different. There was a decreasing trend in hepatic TAG levels, and histological evaluation of steatosis grade was markedly lower in the livers of mice fed BCE. Although the mRNA levels of major regulators of hepatic cholesterol metabolism, i.e. 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) and LDL receptor (LDLR), were not significantly altered by BCE supplementation, protein expression of mature sterol-regulatory element-binding protein and LDLR was significantly increased with no change in HMGR protein. The expression of proprotein convertase subtilisin/kexin type 9 that facilitates LDLR protein degradation, as well as one of its transcriptional regulators, i.e. hepatocyte nuclear factor 4α, was significantly decreased in the livers of mice fed BCE. Taken together, BCE supplementation decreased plasma TC and glucose, and inhibited liver steatosis, suggesting that this berry may be consumed to prevent metabolic dysfunctions induced by diets high in fat and cholesterol.

High-protein (HP) diets are effective anti-steatotic treatment options for patients with non-alcoholic fatty liver disease, but whether these diets also decrease steatosis in hyperlipidaemic conditions is not known. The aim of the present study was to determine the effects of a HP diet on hepatic steatosis and inflammation in hyperlipidaemic mice. Hyperlipidaemic male and female APOE2 knock-in (APOE2ki) mice were fed a semi-synthetic low-protein (LP) or HP diet in combination with a low-fat diet or a high-fat diet for 3 weeks. The HP diets reduced hepatic fat and cholesterol concentrations to 40–55 % of those induced by the corresponding LP diets and attenuated hepatic inflammation mildly. The VLDL-associated plasma cholesterol concentrations decreased to 60–80 %, but those of TAG increased 3–4-fold. APOE2-mediated restriction of fat import into the liver did not modify the effects of a HP diet previously observed in wild-type mice. Female APOE2ki mice exhibited a higher expression of lipogenic, cholesterol-synthesising, inflammatory and cell-stress genes than wild-type female or male APOE2ki mice, but a similar response to HP diets. Low Apob expression and unchanged plasma APOB100 concentrations suggest that HP diets increase the plasma concentrations of TAG by slowing their clearance. The decrease in plasma leptin and hepatic fat and glycogen concentrations and the increase in fatty acid-oxidising gene and phosphoenolpyruvate carboxykinase 1 protein expression suggest a HP diet-mediated increase in mitochondrial metabolism. In conclusion, a HP diet reduces hepatic lipid content in dyslipidaemic mice and lowers the activation status of inflammatory cells in the liver.

Essential oil components from turmeric (Curcuma longa L.) are documented for neuroprotective, anti-cancer, anti-thrombotic and antioxidant effects. The present study aimed to investigate the disease-modifying potential of curcuma oil (C. oil), a lipophilic component from C. longa L., in hyperlipidaemic hamsters. Male golden Syrian hamsters were fed a chow or high-cholesterol (HC) and fat-rich diet with or without C. oil (30, 100 and 300 mg/kg) for 28 d. In HC diet-fed hamsters, C. oil significantly reduced plasma total cholesterol, LDL-cholesterol and TAG, and increased HDL-cholesterol when compared with the HC group. Similar group comparisons showed that C. oil treatment reduced hepatic cholesterol and oxidative stress, and improved liver function. Hyperlipidaemia-induced platelet activation, vascular dysfunction and repressed eNOS mRNA expression were restored by the C. oil treatment. Furthermore, aortic cholesterol accumulation and CD68 expression were also reduced in the C. oil-treated group. The effect of C. oil at 300 mg/kg was comparable with the standard drug ezetimibe. Delving into the probable anti-hyperlipidaemic mechanism at the transcript level, the C. oil-treated groups fed the chow and HC diets were compared with the chow diet-fed group. The C. oil treatment significantly increased the hepatic expression of PPARα, LXRα, CYP7A1, ABCA1, ABCG5, ABCG8 and LPL accompanied by reduced SREBP-2 and HMGCR expression. C. oil also enhanced ABCA1, ABCG5 and ABCG8 expression and suppressed NPC1L1 expression in the jejunum. In the present study, C. oil demonstrated an anti-hyperlipidaemic effect and reduced lipid-induced oxidative stress, platelet activation and vascular dysfunction. The anti-hyperlipidaemic effect exhibited by C. oil seems to be mediated by the modulation of PPARα, LXRα and associated genes involved in lipid metabolism and transport.

In vitro and in vivo studies have shown that punicic acid, a type of conjugated fatty acid and the main constituent of pomegranate seed oil (PSO), has anti-atherogenic effects. The present study aimed at determining the effect of PSO treatment on serum lipid profiles. This double-blind placebo-controlled randomised clinical trial included fifty-one hyperlipidaemic subjects, diagnosed according to National Cholesterol Education Program definition, and randomly assigned to the PSO and the control groups. The PSO and placebo groups received 400 mg PSO and placebo twice daily, respectively and were followed up for 4 weeks. Serum concentrations of lipids and lipoproteins were measured before and 4 weeks after intervention. Mean concentration of TAG and the TAG:HDL cholesterol (HDL-C) ratio were significantly decreased after 4 weeks in the PSO group as compared with baseline values (2·75 (sd 1·40) v. 3·45 (sd 1·56) mmol/l, P = 0·009 and 5·7 (sd 4·6) v. 7·5 (sd 5·0), P = 0·031, respectively). The treatment effect was statistically significant in the PSO group as compared with controls in diminution of cholesterol:HDL-C ratio (5·4 (sd 1·5) v. 5·9 (sd 1·4), P < 0·05) adjusted for baseline values. We found a mean difference for PSO v. placebo in HDL-C concentration (0·13 v. − 0·02 mmol/l) and cholesterol:HDL-C ratio ( − 0·42 v. 0·01, P < 0·05). Serum cholesterol, LDL cholesterol and glucose concentrations and body composition variables remained unchanged. It is concluded that administration of PSO for 4 weeks in hyperlipidaemic subjects had favourable effects on lipid profiles including TAG and TAG:HDL-C ratio.

The slow digestible disaccharide isomaltulose (iso; Palatinose™) is available as novel functional carbohydrate ingredient for manufacturing of low glycaemic foods and beverages. Although basically characterised, various information on physiological effects of iso are still lacking. Thus, the objective of the present study was to expand scientific knowledge of physiological characteristics of iso by a set of three human intervention trials. Using an ileostomy model, iso was found to be essentially absorbed, irrespective of the nature of food (beverage and solid food). Apparent digestibility of 50 g iso from two different meals was 95·5 and 98·8 %; apparent absorption was 93·6 and 96·1 %, respectively. In healthy volunteers, a single dose intake of iso resulted in lower postprandial blood glucose and insulin responses than did sucrose (suc), while showing prolonged blood glucose delivery over 3 h test. In a 4-week trial with hyperlipidaemic individuals, regular consumption of 50 g/d iso within a Western-type diet was well tolerated and did not affect blood lipids. Fasting blood glucose and insulin resistance were lower after the 4-week iso intervention compared with baseline. This would be consistent with possible beneficial metabolic effects as a consequence of the lower and prolonged glycaemic response and lower insulinaemic burden. However, there was no significant difference at 4 weeks after iso compared with suc. In conclusion, the study shows that iso is completely available from the small intestine, irrespective of food matrix, leading to a prolonged delivery of blood glucose. Regular iso consumption is well tolerated also in subjects with increased risk for vascular diseases.

The diet consumed by urban residents in modern China has become rich in saturated fats and cholesterol. In addition, the diet is high in carbohydrates from white rice and processed wheat starch. The aim of the present study was to determine the effects of replacing white rice and processed wheat starch with wild rice (WR) as the chief source of dietary carbohydrates. Rats fed with the diet patterned after the diet consumed by city residents of modern China showed elevated serum lipid levels comparable with rats consuming a high fat/cholesterol diet known to induce hyperlipidaemia in this species. Meanwhile, rats consuming the city diet with WR as the carbohydrate source suppressed the increase in serum TAG and total cholesterol, and the decrease in HDL cholesterol level. In addition, the rats fed the WR diet suppressed the build-up of oxidative stress by improving antioxidant capacity, increasing superoxide dismutase activity and reducing malondialdehyde concentration, both in the serum and liver. These findings illustrate that WR is effective in suppressing hyperlipidaemia and oxidative stress in rats even when the diet consumed is high in fat and cholesterol.

The present study involved a comparative analysis of the effects of purified flaxseed lignans, secoisolariciresinol diglucoside (SDG) and its aglycone metabolite (SECO), in hyperlipidaemic rats. For hypercholesterolaemia, female Wistars (six rats per group) were fed a standard or 1 % cholesterol diet and orally administered 0, 3 or 6 mg SDG/kg or 0, 1·6 or 3·2 mg SECO/kg body weight once daily for 4 weeks. Hypertriacylglycerolaemia was induced in male Sprague–Dawley rats (ten rats per group) by supplementing tap water with 10 % fructose. These rats were orally administered 0, 3 or 6 mg SDG/kg body weight once daily for 2 weeks. Fasting blood samples (12 h) were collected predose and at the end of the dosing period for serum lipid analyses. Rats were killed and livers rapidly excised and sectioned for lipid, mRNA and histological analyses. Chronic administration of equimolar amounts of SDG and SECO caused similar dose-dependent reductions in rate of body-weight gain and in serum total and LDL-cholesterol levels and hepatic lipid accumulation. SDG and SECO failed to alter hepatic gene expression of commonly reported regulatory targets of lipid homeostasis. SDG had no effect on serum TAG, NEFA, phospholipids and rate of weight gain in 10 % fructose-supplemented rats. In conclusion, our data suggest that the lignan component of flaxseed contributes to the hypocholesterolaemic effects of flaxseed consumption observed in humans. Future studies plan to identify the biochemical mechanism(s) through which flaxseed lignans exert their beneficial effects and the lignan form(s) responsible.

We investigated whether the hypolipidaemic effect of fenofibrate and fasting observed in most omnivorous mammals may also apply to herbivorous fish. Grass carp (Ctenopharyngodon idella) fed a high-fat (8 %) diet exhibited a marked increase in blood lipids and body fat after 6 weeks. They were then treated with fenofibrate (100 mg/kg body weight) in the same high-fat diet for 2 weeks, followed by fasting for 1 week. Plasma lipid concentration, body fat amount, fatty acid composition, plasma thiobarbituric acid-reactive substances and some parameters related to hepatic fatty acid oxidation were measured, and liver samples were stained for histological examination. Fenofibrate treatment decreased TAG and cholesterol concentrations in plasma, total lipids of the whole body and liver, and EPA and DHA contents in tissues. Further, a mobilisation of mesenteric fat concomitant with an increase in hepatic peroxisomal fatty acid oxidation and lipid peroxidation was observed. Compared with fenofibrate treatment, fasting decreased body weight and plasma TAG, but not plasma cholesterol. It also reduced the fat content of the whole body and increased the EPA and DHA contents in the liver and other tissues. Fatty acid oxidation was stimulated by fasting in mitochondria, but not in peroxisomes. These data suggest that fenofibrate and fasting regulate the lipid metabolism in grass carp through different metabolic pathways. The grass carp is moderately responsive to a fibrate derivative in comparison with the well-known excess responsiveness of the rat model, and so it could be used for the study of lipid abnormalities as a herbivorous model.

Aqueous extracts or juice from unripened fruit of Momordica charantia (bitter melon) has traditionally been used in the treatment of diabetes and its complications. Insulin resistance is characterized by significant down-regulation of hepatic insulin signalling as documented by attenuated phosphorylation of insulin receptor (IR), IR substrates 1 and 2, phosphoinositide-3 kinase, protein kinase B, and over-expression of phosphotyrosine phosphatase 1B. We recently demonstrated that bitter melon juice (BMJ) is a potent inhibitor of apoB secretion and TAG synthesis and secretion in human hepatoma cells, HepG2, that may be involved in plasma lipid- and VLDL-lowering effects observed in animal studies. The aim of this study was to evaluate the effects of BMJ on plasma apoB levels and hepatic insulin signalling cascade in mice fed high-fat diet (HFD). Female C57BL/6 mice (4–6 weeks old) were randomized into three groups receiving regular rodent chow, HFD and HFD+BMJ. The data indicate that BMJ not only improves glucose and insulin tolerance but also lowers plasma apoB-100 and apoB-48 in HFD-fed mice as well as modulates the phosphorylation status of IR and its downstream signalling molecules. Investigating the biochemical and molecular mechanisms involved in amelioration of diabetic dyslipidaemia by BMJ may lead to identification of new molecular targets for dietary/alternative therapies.