High-fat Diet-induced Hyperlipidemic Rats Research Articles

An Evaluation of Anti-hyperlipidemic Activity of Ethanolic Extract of Moringa oleifera on High Fat Induced Hyperlipidemic Rat Model

Background: The art or practice of herbal remedies refers to the use of herbs and herbal treatments for the purpose of maintaining health and preventing, treating, or curing sickness. In some areas, herbal treatments can also be referred to as herbal medicine.
 Aim: The present study was designed to investigate the antihyperlipidemic and antiatherogenic potentiality of ethanolic extract of Moringa oleifera extract in high fat diet-induced hyperlipidemic rats.
 Materials and Methods: Moringa oleifera ethanolic extract was prepared using Soxhlet apparatus. Male rats were made hyperlipidemic by giving high fat diet. M. oleifera was administered in a dose of 250, 500 and 750 mg/kg.b.w./day for 30 days in high fat diet-induced hyperlipidemic rats. The SGPT, SGOT, total cholesterol,triglyceride, LDL,HDL , Urea and creatinine levels were measured after the treatment.
 Results: For both the SGPT and the SGOT, it was seen that groups 5 and 6 exhibited statistically significant (p< 0.05) outcomes in the case of the SGPT. When conducting the renal function test, it was observed that the levels of creatinine and urea were statistically significant (p< 0.05) in the cases of groups 4, 5, and 6. In the case of high-density lipoprotein (HDL) and low-density lipoprotein (LDL), groups 4, 5, and 6 showed statistically significant findings (p< 0.05) in HDL levels, while groups 5 and 6 showed statistically significant LDL levels. The triglyceride levels in the group were found to be statistically significant (p< 0.05), while the findings obtained from groups 5 and 6 were also found to be statistically significant.
 Conclusion: The study revealed that M. oleifera has anti hyperlipidemic activity.

Antihyperlipidemic and Hepatoprotective Effect of Zingiber Cassumunar Rhizome Extract in High-Fat Diet-Induced Hyperlipidemic Rats: The Role of Antioxidant Activity

Hyperlipidemia and oxidative stress are major risk factors for the onset of cardiovascular diseases, and the oxidative stress caused by high level of lipids can cause liver damage. Zingiber cassumunar has been reported to contain a high antioxidant content that may provide therapeutic advantages. The present study was to evaluate the antihyperlipidemic and hepatoprotective effects of Z. cassumunar rhizome extract (ZCRE) in high-fat diet (HFD)-induced hyperlipidemicrats model and investigate the mechanism through its effect on the endogenous antioxidant enzymes. In this study, the rhizomes of Z. cassumunar was extracted using ethanol 96% (v/v) and evaporated to get the concentrated Z. cassumunar rhizome extract (ZCRE). Thin layer chromatography (TLC)-densitometry was performed to determine the curcumin content in the extract. High fat diet-induced hyperlipidemia model was used to evaluate the anti-hyperlipidemic and hepatoprotectiveactivities of ZCRE in rats. Male Wistar rats were randomly divided into five groups: normal control; High fat diet-induced hyperlipidemic rats (HFD); High Fat Diet and 100 mg/kgBW of ZCRE (HFD + 100 mg/kgBW); High Fat Diet and 200 mg/kgBW of ZCRE (HFD + 200 mg/kgBW); and High Fat Diet and 400 mg/kgBW of ZCRE (HFD + 400 mg/kgBW). The antihyperlipidemic and hepatoprotective potential of ZCRE were assessed through a series of analyses of body weight, blood biochemical parameters, which include total cholesterol (TC), triglycerides (TG), the serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT). The antioxidant activity of catalase (CAT) and glutation peroxidase (GSH-Px) were assessed on the liver homogenate. Data of the study were presented as mean ± SD and analyzed by using one way analysis of variance (ANOVA) followed by Least Significant Difference (LSD) test for multiple comparisons. The TLC analysis showed that ZCRE contained a significant amount of Curcumin. In addition, the study has also shown that ZRCE was able to significantly lower the levels of total cholesterol, triglyceride, SGPT, and SGOT as compared to hyperlipidemic rats (p <0.05). Concomitantly, the activity of CAT and GSH-Px was found significantly increased (p <0.05) when compared to hyperlipidemic control, with the dose of 400 mg/kg BW being the most effective. This study showed the significant antihyperlipidemic and hepatoprotective effects of ZCRE in HFD-induced hyperlipidemic rats, which mechanism might possibly connect to the increased antioxidant enzyme activities.

Hypolipidemic Activity of a Polyherbal Formulation in Triton WR-1339 and High Fat Diet-induced Hyperlipidemic Rats

In hyperlipidemic wistar albino rat models produced by triton and diet, the efficacy of polyherbal formulations containing four different plants was assessed. Rats exposed to Triton WR 1339 had their blood cholesterol and triglyceride levels raised. However, this was reversed when the rats were given syrup or a comparable formulation. Both formulations better lipid outlines in rats with high-fat diet-induced hyperlipidemia. Effects were marginally better with the usual medication Atrovastatin. Liver sinusoidal capillary dilations, cytoplasmic fatty infiltration, and granular degeneration were considerably reduced in polyherbal formulation-treated group II animals related with other groups. As per results, polyherbal formulations in dyslipidaemic circumstances reduce lipid levels by blocking the production of cholesterol and reducing lipid utilization.

Onosma hispidum L. extract reverses hyperlipidemia, hypertension, and associated vascular dysfunction in rats

Onosma hispidum.L (O. hispidum) belongs to the family Boregineacea. A preliminary study and its medicinal use suggested its role in the management of hyperlipidemia. The present study aimed to assess the effect of methanolic root extract of O. hispidum in hyperlipidemia and associated vascular dysfunction. Oral administration of O. hispidum crude extract (Oh. Cr) to tyloxopol and high fat diet-induced hyperlipidemic Sprague-Dawley rats for 10 and 28 days significantly reduced total triglycerides and cholesterol (p < 0.001), compared to hyperlipidemic rats. Oh. Cr 250 mg/kg orally treated rats significantly (p < 0.001) reduced both the total body weight and atherogenic index in tylaxopol and HFD rats. In HMG-CoA assay, the inhibition of the enzyme was significant in Oh.Cr (250 mg/kg) treated group. Histopathological studies indicated that the group treated with Oh.Cr 250 mg/kg/day showed regular morphology of aortic intima, media and adventitia, and improved the endothelial damage. To investigate the vascular dysfunction, isolated rat aorta rings from all groups were pre-contracted with 1 µM phenylephrine (PE), and the effect of acetylcholine (Ach) was monitored. In the aorta isolated from Oh.Cr (50 mg/kg) treated group, Ach completely relaxed the PE-induced contraction with EC50 value of 0.05 µg/mL 0.015 (0.01–0.2) compared to the hyperlipidemic control group (<30% relaxation). In atorvastatin (10 mg/kg) treated rat aorta, Ach showed 50% relaxation. The Oh.Cr extract also reduced (105.92 ± 1.14 to 66.63 ± 0.85 mmHg) mean arterial pressure in hyperlipidemic hypertensive rats. These findings suggest that extract of O. hispidum is an effective remedy for hypercholesterolemia, and hypertriglyceridemia, which acts through inhibition of HMG-CoA and improving vascular dysfunction.

Bacteroides vulgatus Ameliorates Lipid Metabolic Disorders and Modulates Gut Microbial Composition in Hyperlipidemic Rats.

Hyperlipidemia is a risk factor and key indicator for cardiovascular diseases, and the gut microbiota is highly associated with hyperlipidemia. Bacteroides vulgatus is a prevalent mutualist across human populations and confers multiple health benefits such as immunoregulation, antiobesity, and coronary artery disease intervention. However, its role in antihyperlipidemia has not been systematically characterized. This study sought to identify the effect of B. vulgatus Bv46 on hyperlipidemia. Hyperlipidemic rats were modeled by feeding them a high-fat diet for 6 weeks. The effect of B. vulgatus Bv46 supplementation was evaluated by measuring anthropometric parameters, lipid and inflammation markers, and the liver pathology. Multi-omics was used to explore the underlying mechanisms. The ability of B. vulgatus Bv46 to produce bile salt hydrolase was confirmed by gene annotation and in vitro experiments. Oral administration of B. vulgatus Bv46 in hyperlipidemic rats significantly reduced the body weight gain, food efficiency, and liver index, improved the serum lipid profile, lowered the levels of serum inflammatory cytokines, promoted the loss of fecal bile acids (BAs), and extended the fecal pool of short-chain fatty acids (SCFAs), especially propionate and butyrate. B. vulgatus Bv46 induced compositional shifts of the gut microbial community of hyperlipidemic rats, characterized by a lower ratio of Firmicutes to Bacteroidetes with an increase of genera Bacteroides and Parabacteroides. After intervention, serum metabolite profiling exhibited an adaptation in amino acids and glycerophospholipid metabolism. Transcriptomics further detected altered biological processes, including primary bile acid biosynthesis and fatty acid metabolic process. Taken together, the findings suggest that B. vulgatus Bv46 could be a promising candidate for interventions against hyperlipidemia. IMPORTANCE As a core microbe of the human gut ecosystem, Bacteroides vulgatus has been linked to multiple aspects of metabolic disorders in a collection of associative studies, which, while indicative, warrants more direct experimental evidence to verify. In this study, we experimentally demonstrated that oral administration of B. vulgatus Bv46 ameliorated the serum lipid profile and systemic inflammation of high-fat diet-induced hyperlipidemic rats in a microbiome-regulated manner, which appears to be associated with changes of bile acid metabolism, short-chain fatty acid biosynthesis, and serum metabolomic profile. This finding supports the causal contribution of B. vulgatus in host metabolism and helps to form the basis of novel therapies for the treatment of hyperlipidemia.

Supplementation with the Traditional Thai Polyherbal Medicine NawaTab Ameliorates Lipid Profiles in High-Fat Diet-Induced Hyperlipidemic Rats.

A tablet formulation developed from Nawametho decoction (NawaTab), a traditional Thai herbal mixture described in the Worayokasan scripture, has been used clinically for several years in the management of borderline hyperlipidemic individuals. Nevertheless, scientific evidence supporting its claims has never been identified. This study aimed to describe the antihyperlipidemic properties of NawaTab in a well-described model of high-fat diet (HFD)-induced hyperlipidemic rats. Decoction of Nawametho containing equal quantities of Aegle marmelos (L.), Carthamus tinctorius L., Hibiscus sabdariffa Linn., Phyllanthus emblica L., Piper longum L., Piper nigrum L., Terminalia bellirica (Gaertn.) Roxb., Terminalia chebula Retz., and Zingiber officinale Roscoe were prepared. The HFD-fed rats were administered NawaTab for 4 consecutive weeks starting from the ninth week of HFD treatment at a dose of 125 mg/kg (p.o.). Anthropometric parameters, serum lipid profiles, lipase activity, and liver and renal functional markers were measured. Histopathological examination of the liver and any steatosis was carried out at the end of this study. Consecutive treatment with NawaTab (125 mg/kg/day) in HFD-induced hyperlipidemic rats caused a significant reduction in serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels. However, at the tested dose, NawaTab failed to prevent the onset of hepatic steatosis and adipose tissue accumulation. No adverse events due to the consumption of NawaTab on liver and kidney function markers were noted. These findings are the first suggestive evidence for the lipid-lowering capability of NawaTab. However, to promote the use of this formulation in the management of borderline hyperlipidemic patients, elucidation of the underlying mechanisms of action, quantification of biological markers, and clinical trials of NawaTab are urgently needed.

The Hypolipidemic Effect of Hawthorn Leaf Flavonoids through Modulating Lipid Metabolism and Gut Microbiota in Hyperlipidemic Rats.

The purpose of this study was to explore the potential mechanisms of the lipid-regulating effects and the effect on modulating the gut microbiota of hawthorn leaf flavonoids (HLF) in the high-fat diet-induced hyperlipidemic rats. The hypolipidemic effect of HLF was investigated in the high-fat diet-induced hyperlipidemic rats. The action targets of HLF in the treatment of hyperlipidemia were predicted by network pharmacology and KEGG enrichment bubble diagram, which were verified by the test of western blotting. Meanwhile, we used 16S rRNA sequencing to evaluate the effects of HLF on the microbes. The results of animal experiments showed that HLF could reduce the body weight and regulate the levels of serum lipid in high-fat diet (HFD) rats. Meanwhile, for the related targets of cholesterol metabolism, HLF could significantly upregulate the expression of LDLR, NR1H3, and ABCG5/ABCG8; reduce the expression of PCSK9; and increase the level of CYP7A1 in the intestinal tissue, whereas cholesterol biosynthetic protein expressions including HMGCR and SCAP were lowered by HLF. In addition, HLF increased the activities of plasma SOD, CAT, and GSH-Px and decreased the levels of Casp 1, NLRP3, IL-1β, IL-18, and TNF-α, improving the degree of hepatocyte steatosis and inflammatory infiltration of rats. Notably, HLF significantly regulated the relative abundance of major bacteria such as g_Lactobacillus, g_Anaerostipes, g_[Eubacterium]_hallii_group, g_Fusicatenibacter, g_Akkermansia, and g_Collinsella. Synchronously, we found that HLF could regulate the disorder of plasma HEPC and TFR levels caused by HFD. This study demonstrates that HLF can regulate metabolic hyperlipidemia syndromes and modulate the relative abundance of major bacteria, which illustrated that it might be associated with the modulation of gut microbiota composition and metabolites.

Pharmacological effects of Artocarpus lakoocha methanol extract on inhibition of squalene synthase and other downstream enzymes of the cholesterol synthesis pathway

Context Artocarpus lakoocha Roxb. (Moraceae) is reported to possess antioxidant, anti-inflammatory, and anti-skin ageing agents. Objective This study evaluates the pharmacological effects of A. lakoocha leaves methanol extract on enzymes involved in the cholesterol synthesis pathway in high-fat diet-induced hyperlipidemic rats. Materials and methods Twenty-four male Wistar rats, weighing approximately 180–220 g, were divided into four groups: control, diseased (hyperlipidemic), A. lakoocha leaves extract treated, and simvastatin treated. The rats were fed with high-fat diet for 2 months to induce hyperlipidaemia, afterward, experimental groups received A. lakoocha leaves methanol extract (250 mg/kg) and simvastatin (10 mg/kg) orally until the 89th day of the experiment, while the diseased group continued to receive high-fat diet along with normal saline. Results It was found that A. lakoocha extract significantly lowered the serum total cholesterol, triglycerides, and low-density lipoprotein (LDL) levels, while effectively increasing serum high-density lipoprotein (HDL) levels as compared to the diseased group (p ≤ 0.05). The mRNA expression levels of squalene synthase and HMG-CoA reductase were found to be effectively down-regulated after the treatment with A. lakoocha leaves extract (17.45 ± 2.48 vs. 31.91 ± 5.292 and 5.85 ± 3.164 vs. 37.37 ± 6.492) and simvastatin (7.148 ± 0.76 vs. 31.91 ± 5.292, and 3.098 ± 2.09 vs. 37.37 ± 6.492) as compared to the diseased group. Discussion and Conclusions The results suggested that A. lakoocha leaves extract have observable beneficial effects on inhibition of enzymes involved in cholesterol synthesis pathway and improve lipid profile analogous to simvastatin.

Integrative analysis of fecal metabolome and gut microbiota in high-fat diet-induced hyperlipidemic rats treated with Rosa Roxburghii Tratt juice

The 12 weeks of treatment with Rosa Roxburghii Tratt Juice can regulate Dyslipidemia by improving intestinal microbiota disorders and related metabolomics disorders, and their related metabolites might inhibit glycolytic and regulate energy metabolism disorder to improve the states of Dyslipidemia. • Rosa Roxburghii Tratt juice can regulate dyslipidemia by improving intestinal microbiota disorders and related metabolites disorders. • Rosa Roxburghii Tratt juice partially improved dyslipidemia and obesity induced by HFD by increasing Roseburia, Bifidobacterium and reducing Coprobacillus, Dorea levels, as well as reductions in cystine, glyceric acid, palmitoleic acid, propionic acid, and succinic acid-related levels. The fruit of Rosa Roxburghii Tratt (RRT) is edible and has been considered as a medicinal fruit with a lipid-lowering effect, but the mechanism is still unclear. In this study, we integrated the results of 16S rRNA gene sequence and fecal metabolome to explore the potential mechanisms of RRTJ treatment in hyperlipidemia. The result suggests the useful effects of RRT juice (RRTJ) in hyperlipidemic rats. The 12 weeks of RRT juice (RRTJ) treatment decreased serum lipids, fat accumulation, body weight and liver weight. RRTJ treatment reversed the HFD-induced gut dysbiosis by lowering Dorea, Coprobacillus abundance and enriching Bifidobacterium, Roseburia abundance. Also, we conducted a targeted metabolic profile analysis of 160 metabolites in feces and 19 feces metabolites have significant changes. Correlation analyses suggest that the reductions in serum lipids by RRTJ are associated with the gut microbial community (Dorea, Coprobacillus and Roseburia, Bifidobacterium) and their associated metabolites (palmitoleic acid, succinic acid, propionic acid, Glyceric acid). In conclusion, the 12 weeks of treatment with RRT juice (RRTJ) can regulate dyslipidemia by improving intestinal microbiota disorders and related metabolites disorders.

Effects of Gongronema latifolium Benth and Celosia argentea Linn supplemented diet on the hepatic and cardiac functions of high-fat diet-induced hyperlipidemic rats

PurposeThe purpose of this study is to assess the effects of two green leafy vegetables (Gongronema latifolium and Celosia argentea) on the hepatic biomarkers [Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)], cardiac biomarkers [Creatine Kinase (CK) and Lactate Dehydrogenase (LDH)] and histopathology of the heart of high-fat diet-induced hyperlipidemic rats, with the aim of evaluating the vegetables as functional foods.Design/methodology/approachExperimental diets consisted of Control Diet (CD), High-Fat Diet (HFD), High-Fat Diet with Blanched Celosia argentea (HCB), High-Fat Diet with Unblanched Celosia argentea (HCU), High-Fat diet with Blanched Gongronema latifolium (HGB) and High-Fat Diet with Unblanched Gongronema latifolium (HGU). Seventy-five albino male rats (weighing 180–200 g) were used. The animals were divided into 15 groups of five albino rats each. Animals in Groups 1, 2 and 3 were fed with CD, HFD only and HFD with Atorvastin (5 mg/kg b.w), respectively. Animals in Groups 4, 5 and 6 were fed with 5, 10 and 15% HCB, respectively. Animals in Groups 7, 8 and 9 were fed with 5, 10 and 15% HCU, respectively, whereas animals in Groups 10, 11 and 12 were fed with 5, 10 and 15% HGB, respectively, and animals in Groups 13, 14 and 15 were fed with 5, 10 and 15% diet-inclusion of HGU, respectively.FindingsThe incorporation of the vegetal matter into the diet brought about a significant reduction (p = 0.05) in the activities of ALT, AST, CK and LDH when compared with HFD. However, the histological examination showed no pathological lesion, only at 15% inclusion of the vegetables.Originality/valueThe paper established that the incorporation of Celosia argentea and Gongronema latifolium into diet, most especially at 15% inclusion, may serve as functional food in the management of hyperlipidemia and associated complications.

Hypolipidemic effect of prepared Polyherbal formulations in Wistar albino rats

Lipid lowering effect of polyherbal formulations using eight different plants was evaluated in triton and diet induced hyperlipidemic models of wistar albino rats. Formulations such as Tablet, Syrup and Suspension inhibited the elevation in serum cholesterol and triglyceride levels on Triton WR 1339 administration rats. The formulations at the same dose level significantly attenuated the elevated serum total cholesterol and triglycerides with an increase in high-density lipoprotein cholesterol in high-fat diet-induced hyperlipidemic rats. The standard drug Niacin showed slightly better effects. The treatment with herbal formulations produced 30-35 percentage improvement in oral glucose tolerance. Similarly all the formulations also reduced the elevated C-reactive protein which is a marker of Hyperlipidemia. In histopathological study it was found that treatment of polyherbal formulation significantly reduced the plaque size in aorta compared with HFD treated control group. The outcome of the study reveals the lipid lowering activity of polyherbal formulations in dyslipidaemic conditions by interfering with the biosynthesis of cholesterol and utilization of lipids.

Preclinical Pharmacokinetics and Pharmacodynamics of Coptidis Preparation in Combination with Lovastatin in High-Fat Diet-Induced Hyperlipidemic Rats.

Lovastatin is a standard therapy for dyslipidemia. Alternatively, some ethnomedicines, such as Coptidis preparation, have been used for the treatment of dyslipidemia. Statins and complementary and alternative medicines may possess individual mechanisms of action against dyslipidemia. We hypothesize that the combination of Coptidis preparation and lovastatin may have synergistic effects for the treatment of dyslipidemia. To investigate this hypothesis, we developed a validated ultra-high-performance liquid chromatography-tandem mass spectrometry method to monitor lovastatin and its metabolites for pharmacokinetic studies in rats. This study was divided into four groups: lovastatin (10 mg/kg, p.o.) alone and lovastatin (10 mg/kg, p.o.) + Coptidis preparation (0.3, 1, or 3 g/kg, p.o.) for five consecutive days. In pharmacodynamic studies, a high-fat diet (HFD) was used to induce dyslipidemia in experimental rat models. The HFD rats were divided into four groups: treatment with HFD, HFD + lovastatin (100 mg/kg, p.o.), HFD + Coptidis preparation (1 g/kg, p.o.), and HFD + lovastatin (50 mg/kg, p.o.) + Coptidis preparation (1 g/kg, p.o.) for 28 consecutive days. The pharmacokinetic results demonstrated that Coptidis preparation significantly augmented the conversion of lovastatin into its main metabolite lovastatin acid in vivo. The pharmacodynamic results revealed that the Coptidis preparation and half-dose lovastatin group reduced the body weight, liver weight, and visceral fat in HFD rats. These findings provide constructive preclinical pharmacokinetic and pharmacodynamic applications of Coptidis preparation on the benefit of hyperlipidemia.

Antioxidant activities of Celosia argentea Linn and Gongronema latifolium Benth and the antihyperlipidemic effect of the vegetable supplemented diets on fat induced hyperlipidemic rats

The present study investigated the antioxidant activities and antihyperlipidemic effects of varying levels of inclusion of processed green leafy vegetables (Celosia argentea and Gongronema latifolium) on high fat diet-induced hyperlipidemic rats. The antioxidant assay revealed that the unblanched C. argentea had higher total phenolic content, total flavonoid content, DPPH·, ABTS·+, OH· and NO· radical scavenging activities than the blanched Celosia argentea. Conversely, the blanched G. latifolium had higher antioxidant activities than the unblanched G. latifolium. Seventy-five (75) male albino rats of average weight 180 ± 20 g were divided into fifteen (15) groups of five (5) animals each. The rats were fed for 4 weeks on diets specially formulated to contain 5%, 10% and 15% by weight of the leaves of the blanched and unblanched vegetables. lipid profile (TC: total cholesterol, TG: triglycerides, LDL: low density lipoproteins, VLDL: very low density lipoproteins and HDL: high density lipoproteins) and oxidative stress indicators were evaluated. The serum TC, TG, LDL and VLDL which significantly increased (p < 0.0001) in hyperlipidemic control group were significantly decreased (p < 0.05, 0.0001) at all levels of inclusion of the vegetal diets. HDL also increased significantly (p < 0.0001) in groups fed with the vegetal diets. In addition, glutathione peroxidase, reduced glutathione, catalase and superoxide dismutase activities significantly increased (p < 0.05, 0.0001); while TBARS significantly decreased at all levels of inclusion of the vegetal diets. These results suggested that incorporation of C. argentea and G. latifolium into the diet most especially blanched C. argentea and unblanched G. latifolium may have therapeutic potentials in the management of hyperlipidemia and associated complications.

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet.

The objective of this study was to investigate the effects of simvastatin (SIM) on lipid metabolism disorders and gut microbiota in high-fat diet-induced hyperlipidemic rats. The obtained results revealed that feeding rats with SIM (20 mg/kg/day) significantly decreased serum lipid level and inhibited hepatic lipid accumulation and steatosis. Histological analysis further indicated that SIM reduced lipid deposition in adipocytes and hepatocytes in comparison with that of the HFD group. The underlying mechanisms of SIM administration against HFD-induced hyperlipidemia were also studied by UPLC-Q-TOF/MS-based liver metabonomics coupled with pathway analysis. Metabolic pathway enrichment analysis of liver metabolites with significant difference in abundance indicated that fatty acids metabolism and amino acid metabolism were the main metabolic pathways altered by SIM administration. Meanwhile, operational taxonomic units (OTUs) analysis revealed that oral administration of SIM altered the composition of gut microbiota, including Ruminococcaceae (OTU960) and Lactobacillus (OTU152), and so on. Furthermore, SIM treatment also regulated the mRNA levels of the genes involved in lipid and cholesterol metabolism. Immunohistochemistry (IHC) analysis of the liver-related proteins (CD36, CYP7A1 and SREBP-1C) showed that oral administration of SIM could regulate the levels of the protein expression related to hepatic lipid metabolism.

Effects of metformin on high-fat diet-induced hyperlipidemic rats

Metformin as insulin sensitizer is now often associated with a significant decrease in plasma triglycerides, plasma total cholesterol, LDL cholesterol, and a significant increase in plasma HDL cholesterol without causing hypoglycemia. Current research aim are to determine the effects of metformin on high-fat diet-induced hyperlipidemic rats. To this end, a total of 30 Sprague-Dawley rats were divided into six groups (N = 5). Normal control was not treated, the negative group was given 0.5% CMC, the positive group used simvastatin dose of 1.8 mg/kg BW/day orally and three variation dose groups of metformin were given at a dose of 225; 450; and 900 mg/kg BW rat/day orally. Induction was carried out for 28 days and continued for 14 days treated with an administration orally. Lipid profile was measured by the colorimetric enzymatic method. As a result, all doses of metformin significantly decreased total cholesterol and LDL (p <0.05) compared to normal and negative controls. The highest dose significantly decreased triglyceride levels (p <0.05) and increased HDL levels (p <0.05) compared to normal and negative controls. Based on these results, metformin has a potential effect of antihyperlipidemic at a dose of 225 mg/kg BW rat.

Antihyperlipidemic effects of apple peel extract in high-fat diet-induced hyperlipidemic rats

Hyperlipidemia is generally managed with statin-based drugs. Simvastatin serves as a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitor, with prolonged use proven to cause side effects. In the present study, antihyperlipidemic material is tested for its effect in lowering lipid in animals and its proven ability to bind to HMGR. Hyperlipidemia rats were divided into four groups, with different doses of 0, 57, and 114 mg/kg BW of apple peel extract (APE) and simvastatin (3.6 mg/kg BW). The total cholesterol (TC), total triglyceride (TG), low-density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol (HDLc) serum were measured. In silico inhibition test of HMGR activity was conducted by molecular docking using PyRx software. This process places HMGR as a receptor and active compound of apple peels as a ligand. APE treatment with a dose of 114 mg/kg BW could significantly reduce LDLc and increase serum HDLc levels. Docking tests confirmed that quercetin, chlorogenic acid, epicatechin, and catechins depicted HMGR inhibition. Quercetin could bind to HMGR at a similar location to amino acid residues as simvastatin. These material extracts have inhibited cholesterol synthesis through a stronger HMGR inhibition than simvastatin.

The protective mechanisms of macroalgae Laminaria japonica consumption against lipid metabolism disorders in high-fat diet-induced hyperlipidemic rats.

Macroalgae Laminaria japonica (MLJ) has been reported to exhibit various biological activities including improving immunity, anti-aging, anti-tumor, anti-atherosclerosis and anti-diabetic, but the protective mechanisms of MLJ consumption against non-alcoholic fatty liver disease (NAFLD) associated with hyperlipidemia remain poorly understood. This study demonstrated that MLJ consumption prevented high-fat diet (HFD)-induced NAFLD associated with hyperlipidemia in a rat model, and improved hyperlipidemia-related parameters, e.g. serum and hepatic lipid profiles. Moreover, histological analysis showed that MLJ reduced lipid deposition in adipocytes and hepatocytes compared with the HFD group. Such beneficial effects may be associated with the modulation of the intestinal microbiota, especially some key microbial phylotypes involved in lipid metabolism homeostasis. The underlying protective mechanisms of MLJ consumption against HFD-induced NAFLD associated with hyperlipidemia were also studied by ultra-high performance liquid chromatography with quadruple-time of flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics coupled with pathway analysis. The metabolic pathway enrichment analysis of the differentially abundant hepatic metabolites indicated that primary bile acid biosynthesis metabolism and cysteine and methionine metabolism were the two main metabolic pathways altered by MLJ consumption when compared with the model group. The analysis of the transcription levels of liver-related genes by RT-qPCR and the expressions of liver-related proteins by immunohistochemistry (IHC) showed that MLJ consumption could regulate the levels of mRNA transcription and protein expression related to hepatic lipid metabolism. In short, this study indicates that MLJ could be developed as functional food supplement for the prevention or treatment of NAFLD associated with hyperlipidemia.

Antiobesity, Regulation of Lipid Metabolism, and Attenuation of Liver Oxidative Stress Effects of Hydroxy-α-sanshool Isolated from Zanthoxylum bungeanum on High-Fat Diet-Induced Hyperlipidemic Rats.

Zanthoxylum bungeanum is a traditional Chinese medicine (TCM) used to relieve pain, dispel dampness, stop diarrhea, and prevent itching. The aim of this study was to investigate the antiobesity and hypolipidemic effects of hydroxy-α-sanshool (HAS) isolated from Z. bungeanum on hyperlipidemic rats. Wistar rats (n = 48) were randomly divided into six groups: (1) normal diet rats (ND), (2) high-fat diet- (HFD-) treated rats, (3) HFD+fenofibrate-treated rats (HFD+FNB), (4) HFD+low dose of HAS-treated rats (HFD+LD, 9 mg/kg), (5) HFD+middle dose of HAS-treated rats (HFD+MD, 18 mg/kg), and (6) HFD+high dose of HAS-treated rats (HFD+HD, 36 mg/kg). The body weight and food intake of the rats were recorded during the treatment period. After 4 weeks of HAS treatment, abdominal adipose tissues were observed and total cholesterol (T-CHO), triglycerides (TG), high-density lipoprotein (HDL) cholesterol (HDL-C), and low-density lipoprotein (LDL) cholesterol (LDL-C) of serum and liver tissues were determined. Furthermore, histochemical examinations using oil red O and hematoxylin-eosin staining (H&E) were carried out and levels of malondialdehyde (MDA) and glutathione (GSH) and activities of superoxide dismutase (SOD) in the liver were determined. After HFD feeding, the body weight gain and food efficiency ratio of HFD rats were significantly enhanced (p < 0.05vs. ND rats) and HAS treatment (18 and 36 mg/kg) significantly decreased the body weight gain and food efficiency ratio (p < 0.05vs. HFD rats). In addition, HAS treatment could decrease the abdominal adipose tissues and liver adipocytes. Furthermore, HAS treatment significantly decreased the T-CHO, TG, and LDL-C, whereas it increased HDL-C (p < 0.05vs. HFD rats) in serum and the liver. HAS treatment increased the GSH level and SOD activity in the liver (p < 0.05vs. HFD rats), whereas it decreased the levels of MDA (p < 0.05vs. HFD rats). mRNA analyses suggested that HAS treatment increases the expression of Pparg (proliferator-activated receptor γ) and Apoe (peroxisome apolipoprotein E). Immunohistochemistry and Western blotting indicated that HAS stimulation increased the levels of PPARγ and APOE in the liver, as a stress response of the body defense system. These results revealed that HAS exerts antiobesity and hypolipidemic activities in HFD rats by reducing liver oxidative stress and thus could be considered as a potential candidate drug to cure or prevent obesity and hyperlipidemia.

44-LB: Hypothalamic Glucocorticoid Action Regulates Lipid Metabolism

Aberrant lipid homeostasis is a feature of diabetes and obesity. This metabolic imbalance is associated with excessive levels and/or actions of glucocorticoids (GCs) and contributes to dyslipidemia including elevated hepatic triglyceride (TG)-rich very low-density lipoprotein (VLDL-TG) secretion. The mediobasal hypothalamus (MBH) is a nutrient and hormone sensing brain region that regulates whole-body lipid metabolism and VLDL-TG secretion. We aimed to assess GC action in the MBH in regulating VLDL-TG secretion in health and diet-induced hyperlipidemia. Sprague Dawley rats received stereotaxic MBH cannulation and vascular catheterizations to enable direct MBH infusions, intravenous injections, and blood sampling. Plasma TG levels and the rate VLDL-TG secretion were measured in 10h-fasted rats following intravenous poloxamer injection with concomitant MBH infusions. In healthy rats, direct MBH GC infusion increased VLDL-TG secretion compared to controls. MBH GC action is mediated via its receptor (GR) since mifepristone (GR antagonist) co-infusion, chronic inhibition of GRs in the MBH with GR shRNA, or inhibition of heat shock protein 90 (required for in vivo GR function) negated the MBH GC-induced increases in VLDL-TG secretion rate. High-fat diet-fed rats had both elevated basal plasma GC levels and hepatic TG secretion compared to healthy rats. Remarkably, chronic MBH GR loss-of-function lowered VLDL-TG secretion in high-fat diet-induced hyperlipidemic rats, independent of changes in body weight. Here, we provide novel in vivo evidence that MBH GC action modulates VLDL-TG secretion and suggest that blocking excessive GC action in the brain improves lipid homeostasis in diet-induced hyperlipidemic rats. These findings may provide insight on lowering lipid levels in diabetes and obesity. Disclosure M. Cardoso: None. M. Wang: None. E. Ling: None. H. Lee: None. E. Beaulieu-Bayne: None. J.T. Yue: None. Funding Diabetes Canada; Natural Sciences and Engineering Research Council of Canada; Canadian Lipoprotein Conference

Akebia Saponin D Regulates the Metabolome and Intestinal Microbiota in High Fat Diet-Induced Hyperlipidemic Rats.

Hyperlipidemia is a major component of metabolic syndrome, and regarded as one of the main risk factors causing metabolic diseases. We have developed a therapeutic drug, akebia saponin D (ASD), and determined its anti-hyperlipidemia activity and the potential mechanism(s) of action by analyzing the metabolome and intestinal microbiota. Male Sprague-Dawley rats were fed a high fat diet to induce hyperlipidemia, and then given ASD orally for 8 weeks. Lipid levels in serum were determined biochemically. Metabolites in serum, urine and feces were analyzed by UPLC-Q/TOF-MS, and the structure of the intestinal microbiota was determined by 16S rRNA sequencing. The ASD treatment significantly decreased the levels of TC, TG and LDL-c and increased the serum level of HDL-c. Metabolomics analysis indicated that the ASD treatment mainly impacted seven differential metabolites in the serum, sixteen differential metabolites in the urine and four differential metabolites in feces compared to the model group. The ASD treatment significantly changed eight bacteria at the genus level compared to the model group. In conclusion, ASD treatment can significantly alleviate HFD-induced hyperlipidemia and the hypolipidemic effect of ASD treatment is certainly associated with a systematic change in the metabolism, as well as dynamic changes in the structure of the intestinal microbiota.