High-fat Diet-induced Dyslipidemia Research Articles

Limonin alleviates high-fat diet-induced dyslipidemia by regulating the intestinal barrier via the microbiota-related ILC3-IL22-IL22R pathway.

High-fat diet (HFD)-induced dyslipidemia is frequently accompanied by gut microbiota dysbiosis and a compromised gut barrier. Enhancing the intestinal barrier function emerges as a potential therapeutic approach for dyslipidemia. The ILC3-IL22-IL22R pathway, which responds to dietary and microbial signals, has not only attracted attention for its crucial role in maintaining the intestinal barrier, but recent reports have also suggested its potential in regulating lipid metabolism. Limonin is derived from the Chinese herb Evodiae fructus, which has shown potential in ameliorating dysbiosis of serum lipids. However, its underlying mechanisms remain elusive. Consequently, targeting the ILC3-IL22-IL22R pathway to enhance intestinal barrier function holds promise as a therapeutic approach for dyslipidemia. In this study, male C57BL/6 mice were subjected to a 16-week HFD to induce dyslipidemia and concurrently administered oral limonin. We discovered that limonin supplementation dramatically reduced serum lipid profiles in HFD-fed mice, significantly curbing HFD-induced weight gain and epididymal fat accumulation. Ileal histopathological evaluation indicated limonin's ameliorative effects on HFD-induced intestinal barrier impairment. Limonin also moderated the intestinal microbiota dysbiosis, which is characterized by the elevation of Firmicutes in HFD mice, and notably amplified the abundance of probiotic Lactobacillus. In addition, supported by flow cytometry and other analyses, we observed that limonin upregulated the ILC3-IL22-IL22R pathway, enhancing phosphorylated STAT3 (pSTAT3) in intestinal epithelial cells (IECs), thereby reducing lipid transporter expression. In conclusion, our study revealed that limonin exerted a promising preventive effect against HFD-induced dyslipidemia by the mitigation of the intestinal barrier function and intestinal microbiota, and its mechanism was related to the upregulation of the ILC3-IL22-IL22R pathway.

Fu Brick Tea as a Staple Food Supplement Attenuates High Fat Diet Induced Obesity in Mice.

Fu brick tea (FBT), a product of microbial fermentation from primary dark tea, also known as raw material tea (RMT), has been extensively studied for its functional properties. However, its potential as a staple food supplement for weight loss remains poorly understood. This study compared the weight loss effects of orlistat, traditional plain noodles (NN), and noodles supplemented with varying amounts of RMT (RMTN) and FBT (FBTN), with the aim to elucidate their lipid-reducing effects and underlying mechanisms. Experimental trials on high fat diet fed mice revealed significant weight loss, lipid-lowering, and hypoglycemic effects upon supplementation with orlistat, RMTN, and FBTN. Moreover, supplementation with orlistat, RMTN, and FBTN effectively restored serum and liver-related index levels, mitigating high-fat diet-induced dyslipidemia. Additionally, these supplements ameliorated liver and kidney damage by inhibiting oxidative stress and inflammatory responses. Furthermore, orlistat, RMTN, and FBTN exert their anti-obesity effects primarily by modulating genes associated with lipid metabolism and inflammatory responses and through regulation of the composition and structure of the gut microbiota. Importantly, FBTN demonstrated a significantly stronger lipid-lowering effect compared to RMTN, particularly at higher tea addition ratios. In contrast, NN supplementation exhibited minimal to no weight loss effects. Based on these findings, it could be inferred that FBT holds promise as a staple food supplement to ameliorate high-fat diet-induced obesity and its associated health conditions.

Ligustilide covalently binds to Cys129 of HMGCS1 to ameliorate dyslipidemia

Dyslipidemia is characterized by elevated levels of total cholesterol and triglycerides in serum, and has become the primary human health killer because of the major risk factors for cardiovascular diseases. Although there exist plenty of drugs for dyslipidemia, the number of patients who could benefit from lipid-lowering drugs still remains a concern. Ligustilide (Lig), a natural phthalide derivative, was reported to regulate lipid metabolic disorders. However, its specific targets and underlying molecular mechanism are still unclear. In this study, we found that Lig alleviated high fat diet-induced dyslipidemia by inhibiting cholesterol biosynthesis. Furthermore, a series of chemical biological analysis methods were used to identify its target protein for regulating lipid metabolism. Collectively, 3-hydroxy-3-methylglutaryl coenzyme A synthetase 1 (HMGCS1) of hepatic cells was identified as a target for Lig to regulate lipid metabolism. The mechanistic study confirmed that Lig irreversibly binds to Cys129 of HMGCS1 via its metabolic intermediate 6,7-epoxyligustilide, thereby reducing cholesterol synthesis and improving lipid metabolism disorders. These findings not only systematically elucidated the lipid-lowering mechanism of Lig, but also provided a new structural compound for the treatment of dyslipidemia.

Ganoderma lucidum polysaccharides improve lipid metabolism against high-fat diet-induced dyslipidemia.

As a kind of traditional medicinal fungi, Ganoderma lucidum has been employed as folk medicine in China against multiple metabolic diseases on account of its superior bioactivities. Recently, accumulated reports have investigated the protective effects of G. lucidum polysaccharides (GLP) on ameliorating dyslipidemia. However, the specific mechanism by which GLP improves dyslipidemia is not completely clear. This study aimed to investigate the protective effects of GLP on high-fatdiet-induced hyperlipidemia and exploring its underlying mechanism. The GLP was successfully obtained from G. lucidum mycelium. The mice were conducted with high-fatdiet to establish the hyperlipidemia model. Biochemical determination, histological analysis, immunofluorescence, western blot and real-time qPCR were used to assess the alterations in high-fatdiet-treated mice after the GLP intervention. It was found that GLP administration significantly decreased body weight gain and the excessive lipid levels, and partly alleviated tissue injury. Oxidative stress and inflammations were efficiently ameliorated after the treatment of GLP by activing Nrf2-Keap1 and inhibiting NF-κB signal pathways. GLP promoted cholesterol reverse transport by LXRα-ABCA1/ABCG1 signaling, increased the expressions of CYP7A1 and CYP27A1 responsible for bile acids production, accompanied by inhibition of intestinal FXR-FGF15 levels. Besides, multiple target proteins involved in lipid metabolism were also significantly modulated under the intervention of GLP. Taken together, our results suggested that GLP showed potential lipid-lowering effects and its possible mechanism was involved in improving oxidative stress and inflammation response, modulating bile acids synthesis and lipid regulatory factors, and promoting reverse cholesterol transport, thereby suggesting that GLP may possibly used as a dietary supplement or medication for the adjuvant therapy for hyperlipidemia.

Atorvastatin Inhibits High-Fat Diet-Induced Lipid Metabolism Disorders in Rats by Inhibiting Bacteroides Reduction and Improving Metabolism.

The prevalence of hyperlipidemia and related illnesses is on its rise, and atorvastatin is the frequently used hypolipidemic agent. However, there is still uncertainty about the mechanisms, especially the relationship between the lipid-lowering effect, intestinal microbiome, and metabolic profiles. We aim to intensively explain the mechanism of the hypolipidemic effect of atorvastatin through multi-omics perspective of intestinal microbiome and metabolomics. Multi-omics methods play an increasingly important role in the analysis of intestinal triggers and evaluation of metabolic disorders such as obesity, hyperlipidemia, and diabetes. Therefore, we were prompted to explore intestinal triggers, underlying biomarkers, and potential intervention targets of atorvastatin in the treatment of dyslipidemia through multi-omics. To achieve this, SPF Wistar rats were fed a high-fat diet or normal diet for 8 weeks. Atorvastatin was then administered to high-fat diet-fed rats. By altering intestinal microbiome, a high-fat diet can affect feces and plasma metabolic profiles. Treatment with atorvastatin possibly increases the abundance of Bacteroides, thereby improving "propanoate metabolism" and "glycine, serine and threonine metabolism" in feces and plasma, and contributing to blood lipid reduction. Our study elucidated the intestinal triggers and metabolites of high-fat diet-induced dyslipidemia from the perspective of intestinal microbiome and metabolomics. It equally identified potential intervention targets of atorvastatin. This further explains the mechanism of the hypolipidemic effect of atorvastatin from a multi-omics perspective.

Ormona® SI and Ormona® RC—New Nutraceuticals with Geranylgeraniol, Tocotrienols, Anthocyanins, and Isoflavones—Decrease High-Fat Diet-Induced Dyslipidemia in Wistar Rats

Dyslipidemia is a metabolic condition linked to increased morbidity. This study aimed to evaluate the effect of two new nutraceuticals derived from annatto (Bixa orellana), açaí (Euterpe oleracea), and soybean germ or red clover isoflavones (Trifolium pratense) against high-fat-induced dyslipidemia in female Wistar rats. The formulations were assessed through GC-MS and HPLC-UV/Vis. Next, female Wistar rats received daily administrations of coconut oil and were treated with Ormona® SI (OSI), Ormona® RC (ORC), soybean germ (SG), simvastatin (simv.), simvastatin + Ormona® SI (simv. + OSI), or only distilled water (control). Biochemical tests were performed using the animals’ blood, and their arteries were screened for atheroma formation. The results show abnormal TC, TG, LDL, and HDL levels caused by the high-fat diet, increased glucose levels, hepatotoxicity, nephrotoxicity, and atherogenesis. The nutraceuticals significantly ameliorated all conditions, with results that are similar to the group treated with simvastatin. Notably, the groups treated with either Ormona® or simvastatin + Ormona® had better liver protection than those treated only with SG or simvastatin; additionally, the nutraceuticals could prevent atherogenesis, unlike SG. The results indicate a high efficacy of the nutraceuticals in preventing dyslipidemia and its complications.

Ameliorating mechanism of nuciferine on high-fat diet-induced dyslipidemia and hepatic steatosis by regulating intestinal absorption and serum extracellular vesicles in rats

We investigated the effects of nuciferine rich in Lotus leaf on the amelioration of hepatic steatosis and dyslipidemia of hyperlipidemic rats, and explored the underlying mechanism on miRNAs and genes expression. Serum extracellular vesicles (EVs) from rats were prepared and characterized, and interactions between miRNAs and target mRNAs were validated in 293T cell line with the double luciferase reporter gene assay. Results showed that nuciferine significantly induced the expression of PPARα, ABCA1, CYP7A1, LXRα in liver and ABCG5 in intestine, while NPC1L1 expression was markedly reduced. In vitro, double luciferase reporter assays showed that miRNA-764-5p, miRNA-758-3p, and miRNA-126-5p interacted with the target mRNAs of PPARα, ABCA1, and CYP7A1, respectively. And the effect of nuciferine on lipid metabolism in rats was related to regulate intestinal absorption and serum EVs miRNAs. These miRNAs were able to reduce lipid levels by targeting lipid metabolism genes and up-regulating PPARα-LXRα-ABCA1 pathway and CYP7A1 expression.

Evaluation of the anti-hyperlipidemic effects of Triphala in high fat diet fed rats

Abstract Background: Hyperlipidemia is one of the major risk factors for coronary heart disease and stroke. Triphala, a polyherbal Ayurvedic formulation made from dried fruits of Haritaki (Terminalia chebula Retz.), Bibhitaki (Terminalia bellirica Roxb.), and Amalaki (Phyllanthus emblica Gaertn.) has been suggested to be useful in mitigating hyperlipidemia. In the Ayurveda texts, depending on the patient’s condition and body type, Triphala is formulated and used in one of the two combination (1:1:1 and 1:2:4 of individual constituents) forms. Aims: The present study aimed at evaluating the efficacy of two combinations (1:1:1 and 1:2:4 of individual constituents) of Triphala against high fat diet induced-hyperlipidemia in rats. Materials and method: Hyperlipidemia was induced in Spraque−Dawley albino rats by feeding them with high fat diet. The animals were concomitantly administered with graded dose of one of the two combination (combination of Haritaki, Bibhitaki, and Amalaki in ratio of 1:1:1 or 1:2:4, respectively) of Triphala (250, 500, or 1000 mg/kg body wt.) or atorvastatin. The animals were sacrificed on day 22 and serum was processed for lipid profile and the liver for lipid peroxidation. The statistical analysis was performed by the mean analysis of variance followed by Dunnet’s test. Results: The results indicated that when compared to placebo group, levels of serum total cholesterol, and triglyceride were significantly lower, while high-density lipoprotein cholesterol increased in both the Triphala combination and atorvastatin groups. Of the two groups of Triphala, the formulation having 1:2:4 ratio was better than the 1:1:1. The group having highest drug dose (1000 mg/kg body wt.) of 1:2:4 formulation was better than atorvastatin in rectifying high fat diet-induced dyslipidemia and the atherogenic index was equal to that of atorvastatin. Conclusions: The results of the study indicate that of the two Triphala formulations, the 1:2:4 ratio was better than the 1:1:1 ratio for anti-hyper-lipidemic effects.

Metabonomic Study on the Plasma of High-Fat Diet-Induced Dyslipidemia Rats Treated with Ge Gen Qin Lian Decoction by Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry.

Gegen Qinlian decoction (GGQLD) has a definite effect on T2DM in clinic, and it has the effect of lowering blood sugar, improving insulin resistance, and improving the blood lipid level of rats with dyslipidemia, but the intervention mechanism of GGQLD on dyslipidemia has not been clarified. The changes in endogenous metabolites in the plasma of high-fat diet-induced dyslipidemia rats treated with Ge Gen Qin Lian Decoction (GGQLD) were studied to elucidate the therapeutic effects and mechanism of action of GGQLD in dyslipidemia. Based on ultrahigh-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS), the metabolic profiles of rat serum samples were collected. The rat model of dyslipidemia was induced by a 60% fat-fed high-fat diet. After feeding the rats with a high-fat diet for 4 weeks, dyslipidemia appeared. After 5 weeks of GGQLD (14.85 g kg−1) administration, the metabonomics of rats' plasma samples in the normal group, model group, and administration group were analyzed. Mass profiler professional (MPP), SIMCA-P 14.1, and Graphpad prism 6.0 software were used combined with METLIN biological database and human metabolite database HMDB to screen and identify endogenous biomarkers. Metaboanalyst 4.0 software was used by combining with HMDB and KEGG databases; the enrichment and metabolic pathway of biomarkers were analyzed to explore the metabolic mechanism of dyslipidemia rats induced by high-fat diet and the intervention mechanism of Gegen Qinlian decoction. After 5 weeks of administration of GGQLD, the levels of serum TC and TG were significantly decreased (P < 0.05, P < 0.01), while HDL-C and LDL-C were not significantly affected. After administration, the food intake of rats in the administration group decreased gradually, and the change trend of body weight gradually slowed down. The metabonomics of rat plasma samples results showed that 23 potential biomarkers including α-linolenic acid, arachidonic acid, and lysophosphatidylcholine were significantly changed in positive ion mode. Studies have shown that GGQLD has a significant lipid-lowering effect on dyslipidemia rats induced by a high-fat diet, and its preventive mechanism is related to tryptophan metabolism, fatty acid biosynthesis, α-linolenic acid metabolism, arachidonic acid, and glycerophosphatidyl metabolism pathway.

Procyanidin B2 prevents dyslipidemia via modulation of gut microbiome and related metabolites in high-fat diet fed mice

• Procyanidin B 2 (PB 2 ) prevents high-fat diet-induced dyslipidemia and LPL activity. • PB 2 regulates gut microbiota and increase SCFAs content in dyslipidemia. • PB 2 modulates twenty lipid metabolism biomarkers. • PB 2 prevents dyslipidemia by reducing the abundance of Bilophila and Proteus. This study aimed to elucidate the underlying mechanisms for the preventive effect of procyanidin B 2 (PB 2 ) on a high-fat diet (HFD)-induced dyslipidemia in C57BL/6 mice through a comprehensive analysis of fecal gut microbiome and plasma metabolomics. PB 2 significantly reduced the levels of lipid metabolism biomarkers and increased the antioxidant abilities and lipoprotein lipase activity in mice fed with HFD ( P < 0.05). Furthermore, the abundance of Blautia genus was increased, and that of Lachnoclostridium , Clostridium , Bilophila , Proteus genera were decreased in the PB 2 group of mice compared to the HFD group of mice. Additionally, purine, unsaturated fatty acids, glycerophospholipids, and bile acids were up-regulated in the HFD fed mice plus PB 2 , and phenylglucuronide was down-regulated. The correlation analysis indicated that the gut microbiome, particularly Bilophila and Proteus genera, were strongly associated with the metabolic pathway modulation, which might have led to the preventive effect of PB 2 on dyslipidemia.

Effects of lycopene on skeletal muscle-fiber type and high-fat diet-induced oxidative stress

Increasing studies report that many natural products can participate in formation of muscle fibers. This study aimed to investigate the effect of lycopene on skeletal muscle-fiber type in vivo and in vitro. C2C12 myoblasts were used in vitro study, and the concentration of lycopene was 10 µM. In vivo, 8-week-old male C57/BL6 mice were used and divided into four groups (n=8): (1) ND: normal-fat diet; (2) ND+Lyc: normal-fat diet mixed with 0.33% w/w lycopene; (3) HFD: high-fat diet; and (4) HFD+Lyc: high-fat diet mixed with 0.33% w/w lycopene. The mice tissue samples were collected after 8 weeks feeding.We found that lycopene supplementation enhanced the protein expression of slow-twitch fiber, succinate dehydrogenase, and malic dehydrogenase enzyme activities, whereas lycopene reduced the protein expression of fast-twitch fibers, lactate dehydrogenase, pyruvate kinase enzyme activities. Moreover, lycopene can promote skeletal muscle triglyceride deposition, enhanced the mRNA expression of genes related to lipid synthesis, reduced the mRNA expression of genes related to lipolysis. And high-fat diet-induced dyslipidemia and oxidative stress were attenuated after lycopene supplementation. Additionally, lycopene supplementation reduced the glycolytic reserve but enhanced mitochondrial ATP production in C2C12 cells.These results demonstrated that lycopene affects the activities of metabolic enzymes in muscle fibers, promotes the expression of slow-twitch fibers, and enhanced mitochondrial respiratory capacity. We speculated that lycopene affects the muscle-fiber type through aerobic oxidation, suggesting that lycopene exerts potential beneficial effects on skeletal muscle metabolism.

Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK-mTORC1 pathway.

Adipogenesis, a critical process that converts adipocyte precursors into adipocytes, is considered a potential therapeutic target for the treatment of obesity. Ezetimibe, a drug approved by the United States Food and Drug Administration, is used for the treatment of hypercholesterolemia. Recently, it was reported to ameliorate high fat diet-induced dyslipidemia in mice and reduce lipid accumulation in hepatocytes through the activation of AMPK. However, the anti-adipogenic effects of ezetimibe and the underlying molecular mechanism have not yet been elucidated. Here, we found that ezetimibe reduced lipid accumulation via activating AMPK during the early phase of adipogenesis. We also observed that ezetimibe inhibited peroxisome proliferator-activated receptor γ, which is a major transcription factor of adipogenesis. Furthermore, ezetimibe-mediated AMPK activation reduced lipid accumulation by inhibiting mTORC1 signaling, leading to the downregulation of lipogenesis-related genes. Mitotic clonal expansion, required for adipogenesis, accelerates cell cycle progression and cell proliferation. We additionally observed that ezetimibe prevented the progression of mitotic clonal expansion by arresting the cell cycle at the G0/G1 phase, which was followed by the inhibition of cell proliferation. Collectively, ezetimibe-mediated inhibition of adipogenesis is dependent on the AMPK-mTORC1 pathway. Thus, we suggest that ezetimibe might be a promising drug for the treatment of obesity.

Fucoidan and galactooligosaccharides ameliorate high-fat diet-induced dyslipidemia in rats by modulating the gut microbiota and bile acid metabolism.

Dyslipidemia is an important risk factor for cardiovascular diseases. Fucoidan (FUC) is a polysaccharide extracted from brown marine algae with various biological activities. Galactooligosaccharides (GOS) are important prebiotics that exert benefits on the intestinal microbiota. The aim of this study was to investigate the effects of FUC and GOS on dyslipidemia in rats by modulating the gut microbiota and bile acid metabolism. Twenty-four male inbred Sprague-Dawley (SD) rats aged 8 wk were fed a normal or high-fat diet (HFD) for 8 wk. During the feeding period, rats were gavaged with normal saline solution, FUC solution (100 mg/kg),or GOS solution (800 mg/kg), or a combination of both once daily. Serum biochemical parameters were determined, and the gut microbiota were analyzed via 16S rRNA gene sequencing. Bile salt hydrolase (BSH) activity in the small intestinal contents was also analyzed. The effects of FUC and GOS on Lactobacillus casei DM8121 were analyzed in vitro. In rats, GOS and FUC supplementation significantly improved serum total cholesterol, low-density lipoprotein cholesterol, lipopolysaccharide, serum total bile acid, hepatic tissue steatosis, aortic arch injury, gut microbiota, serum high-density lipoprotein cholesterol, cholesterol 7-alpha hydroxylase expression in the liver, and BSH activity in the small intestinal contents. In an in vitro experiment, GOS and FUC supplementation significantly increased L. casei DM8121's BSH activity. In rats, FUC and GOS supplementation improved serum dyslipidemia, gut microbiota, BSH activity, and bile acid metabolism-related pathways. In vitro, GOS and FUC supplementation increased L. casei DM8121's BSH activity.

Fucoidan alleviates high-fat diet-induced dyslipidemia and atherosclerosis in ApoEshl mice deficient in apolipoprotein E expression

Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, possesses many biological activities including anti-inflammatory and antioxidant activities. We aimed to investigate the protective effects of fucoidan on dyslipidemia and atherosclerosis in apolipoprotein E-deficient mice (ApoEshl mice) and to elucidate its molecular targets in the liver by using a transcriptomic approach. For 12weeks, ApoEshl mice were fed a high-fat diet (HFD) supplemented with either 1% or 5% fucoidan. Fucoidan supplementation significantly reduced tissue weight (liver and white adipose tissue), blood lipid, total cholesterol (TC), triglyceride (TG), non-high-density lipoprotein cholesterol (non-HDL-C) and glucose levels in HFD-fed ApoEshl mice but increased plasma lipoprotein lipase (LPL) activity and HDL-C levels. Fucoidan also reduced hepatic steatosis levels (liver size, TC and TG levels, and lipid peroxidation) and increased white adipose tissue LPL activity. DNA microarray analysis and quantitative reverse transcription-polymerase chain reaction demonstrated differential expression of genes encoding proteins involved in lipid metabolism, energy homeostasis and insulin sensitivity, by activating Ppara and inactivating Srebf1. Fucoidan supplementation markedly reduced the thickness of the lipid-rich plaque, lipid peroxidation and foaming macrophage accumulation in the aorta in HFD-fed ApoEshl mice. Thus, fucoidan supplementation appears to have anti-dyslipidemic and anti-atherosclerotic effects by inducing LPL activity and inhibiting the effects of inflammation and oxidative stress in HFD-fed ApoEshl mice.

Ameliorative potential of Artemisia Capillaris Formula on nonalcoholic fatty liver disease in rats through regulation of fat metabolism

Background: Artemisia Capillaris Formula (ACF), a traditional Chinese medicinal therapy, has been used clinically in China to treat Nonalcoholic Fatty Liver Disease (NAFLD) for many years. However, the mechanism of action of this treatment on NAFLD is still unknown. The goal of the present study is to test whether Artemisia Capillaris Formula protects against NAFLD through regulation of lipid metabolism. Methods: Rat models of NAFLD were established through consumption of a high-fat diet (HFD) for 8 weeks. 60 rats were randomly divided into 6 groups (10 rats per group): the control (standard diet) group, the model (HFD) group, the polyene phosphatidylcholine treated HFD group, and the ACF-treated HFD groups (high-, medium- and low-dose). During weeks 5−8 of the HFD regimen, drugs were intra-gastrically administrated to selected groups for a total of 4 weeks. Hepatic changes were observed through pathological examination of Hematoxylin and eosin-stained tissues, quantification of lipid metabolites from sera (ALT, AST, ALP activity and TG, TC, HDL-C, LDL-C), and quantification of related gene and protein expression levels by RT-PCR and Western blotting. Results: A high-fat diet promoted obesity and the development of hepatomegaly, hepatosteatosis and dyslipidemia in rats after 8 weeks. Treatment with ACF alleviated hepatosteatosis and also protected against high fat diet-induced dyslipidemia. We found that ACF reduced ALT, AST, ALP, TG, TC, and LDL-C and increased HDL-C levels in sera from treated NAFLD rats. In addition, gene and protein expression levels of FAS and ACC were down-regulated following ACF treatment, whereas expression levels of CPT were up-regulated. Conclusion: ACF ameliorates high-fat diet-induced hepatosteatosis and dyslipidemia in rats by altering lipid metabolism-related gene expression, specifically of FAS, ACC, and CPT.

High-salt in addition to high-fat diet may enhance inflammation and fibrosis in liver steatosis induced by oxidative stress and dyslipidemia in mice.

BackgroundIt is widely known that salt is an accelerating factor for the progression of metabolic syndrome and causes cardiovascular diseases, most likely due to its pro-oxidant properties. We hypothesized that excessive salt intake also facilitates the development of nonalcoholic steatohepatitis (NASH), which is frequently associated with metabolic syndrome.MethodsWe examined the exacerbating effect of high-salt diet on high-fat diet-induced liver injury in a susceptible model to oxidative stress, apoE knockout and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transgenic mice.ResultsHigh-salt diet led to NASH in high-fat diet-fed LOX-1 transgenic/apoE knockout mice without affecting high-fat diet-induced dyslipidemia or hepatic triglyceride accumulation. Additionally, a high-salt and high-fat diet stimulated oxidative stress production and inflammatory reaction to a greater extent than did a high-fat diet in the liver of LOX-1 transgenic/apoE knockout mice.ConclusionsWe demonstrated that high-salt diet exacerbated NASH in high-fat diet-fed LOX-1 transgenic /apoE knockout mice and that this effect was associated with the stimulation of oxidative and inflammatory processes; this is the first study to suggest the important role of excessive salt intake in the development of NASH.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-015-0002-9) contains supplementary material, which is available to authorized users.

Pharmacological Basis for the Medicinal Use of Wrightia tinctoria in Hypertension and Dyslipidemia

This study was aimed to offer a possible pharmacological basis regarding the remedial utilization of Wrightia tinctoria in hypertension and dyslipidemia in certain South Asian traditional systems of medicine, using in vivo and in vitro assays. The aqueous methanolic extract of W. tinctoria seeds (Wt.Cr) caused a dose-dependent (1-10 mg/kg) decrease in arterial pressure in anesthetized rats. In the right atria of isolated guinea pigs, Wt.Cr equally inhibited force and rate of spontaneous atrial contractions. When tested on phenylephrine-, high K(+)-, and low K(+)-induced vasoconstrictions in isolated rat aorta, Wt.Cr produced a concentration-dependent vasorelaxation, the most potent being against low K(+)-induced contraction. It also created a rightward shift in the Ca(++) concentration-response curves and suppressed phenylephrine control peaks in a Ca(++)-free environment. In the rat model of tyloxapol-induced dyslipidemia, Wt.Cr produced a decline in the serum levels of total cholesterol and triglycerides. In high fat diet-induced dyslipidemia, it decreased serum total cholesterol and low-density lipoprotein cholesterol, improved high-density lipoprotein cholesterol, and prevented the increase in average body weights by causing a decrease in diet consumption. These data suggest that Wt.Cr(++) lowers blood pressure through a combination of K(+)-channel opening and Ca(++)-channel blocking effects along with antidyslipidemic and weight-reducing properties.

Chlorella modulates insulin signaling pathway and prevents high-fat diet-induced insulin resistance in mice

AimsThe search for natural agents that minimize obesity-associated disorders is receiving special attention. In this regard, the present study aimed to evaluate the prophylactic effect of Chlorella vulgaris (CV) on body weight, lipid profile, blood glucose and insulin signaling in liver, skeletal muscle and adipose tissue of diet-induced obese mice. Main methodsBalb/C mice were fed either with standard rodent chow diet or high-fat diet (HFD) and received concomitant treatment with CV for 12 consecutive weeks. Triglyceride, free fatty acid, total cholesterol and fractions of cholesterol were measured using commercial assay. Insulin and leptin levels were determined by enzyme-linked immunosorbent assay (ELISA). Insulin and glucose tolerance tests were performed. The expression and phosphorylation of IRβ, IRS-1 and Akt were determined by Western blot analyses. Key findingsHerein we demonstrate for the first time in the literature that prevention by CV of high-fat diet-induced insulin resistance in obese mice, as shown by increased glucose and insulin tolerance, is in part due to the improvement in the insulin signaling pathway at its main target tissues, by increasing the phosphorylation levels of proteins such as IR, IRS-1 and Akt. In parallel, the lower phosphorylation levels of IRS-1ser307 were observed in obese mice. We also found that CV administration prevents high-fat diet-induced dyslipidemia by reducing triglyceride, cholesterol and free fatty acid levels. SignificanceWe propose that the modulatory effect of CV treatment preventing the deleterious effects induced by high-fat diet is a good indicator for its use as a prophylactic–therapeutic agent against obesity-related complications.

Studies on two polyherbal formulations (ZPTO and ZTO) for comparison of their antidyslipidemic, antihypertensive and endothelial modulating activities

BackgroundCardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs.MethodsTo assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and O: Orchis mascula, different animal models including, tyloxapol and high fat diet-induced dyslipidemia and spontaneously hypertensive rats (SHR) were used. Effect on endothelial function was studied using isolated tissue bath set up coupled with PowerLab data acquisition system. The antioxidant activity was carried out using DPPH radical-scavenging assay.ResultsBased on preliminary screening of the ingredients of POL-10 in tyloxapol-induced hyperlipidemic rats, ZPTO and ZTO containing four active ingredients namely; Z, P, T and O were identified for further studies and comparison. In tyloxapol-induced hyperlipidemic rats, both ZPTO and ZTO caused significant reduction in serum triglyceride (TG) and total cholesterol (TC). In high fat diet-fed rats, ZPTO decreased TC, low-density lipoproteins cholesterol (LDL-C) and atherogenic index (AI). ZTO also showed similar effects to those of ZPTO with additional merits being more effective in reducing AI, body weight and more importantly raising high-density lipoproteins. In SHR, both formulations markedly reduced systolic blood pressure, AI and TG levels, ZTO being more potent in reversing endothelial dysfunction while was devoid of cardiac stimulatory effect. In addition, ZTO also reduced LDL-C and improved glucose levels in SHR. In DPPH radical-scavenging activity test, ZTO was also more potent than ZPTO.ConclusionThe modified formulation, ZTO was not only found more effective in correcting cardiovascular abnormalities than ZPTO or POL-10 but also it was free from tachycardiac side-effect, which might be observed because of the presence of Piper nigrum in ZPTO.

Improvement in the High-Fat Diet-Induced Dyslipidemia and Adiponectin Levels by Fish Oil Feeding Combined with Food Restriction in Obese KKAy Mice

The effect on weight reduction of fish oil combined with food restriction in comparison with that of beef tallow was investigated in high-fat diet-induced obese KKAy mice. Although the reduction of body and white adipose tissue weight was similar in the two groups, fish oil increased adiponectin levels in the plasma, improved dyslipidemia accompanied by suppression of lipid synthesis in the liver when compared with beef tallow.