High-fat Diet-induced Hyperlipidemia Research Articles

Hypolipidemic mechanism of Pleurotus eryngii polysaccharides in high-fat diet-induced obese mice based on metabolomics.

In this study, the structure of Pleurotus eryngii polysaccharides (PEPs) was characterized, and the mechanism of PEP on obesity and hyperlipidemia induced by high-fat diet was evaluated by metabonomic analysis. The structure of PEPs were characterized by monosaccharide composition, Fourier transform infrared spectroscopy and thermogravimetry. In animal experiments, H&E staining was used to observe the morphological difference of epididymal adipose tissue of mice in each group. Ultrahigh performance liquid chromatography (UHPLC)-(QE) HFX -mass spectrometry (MS) was used to analyze the difference of metabolites in serum of mice in each group and the related metabolic pathways. The PEPs contained nine monosaccharides: 1.05% fucose, 0.30% arabinose, 17.94% galactose, 53.49% glucose, 1.24% xylose, 23.32% mannose, 1.30% ribose, 0.21%galacturonic acid, and 1.17% glucuronic acid. The PEPs began to degrade at 251°C (T0), while the maximum thermal degradation rate temperature (Tm) appeared at 300°C. The results histopathological observation demonstrated that the PEPs had signifificant hypolipidemic activities. After PEPs intervention, the metabolic profile of mice changed significantly. A total of 29 different metabolites were selected as adjunctive therapy to PEPs, for treatment of obesity and hyperlipidemia-related complications caused by a high-fat diet. These metabolites include amino acids, unsaturated fatty acids, choline, glycerol phospholipids, and other endogenous compounds, which can prevent and treat obesity and hyperlipidemia caused by a high-fat diet by regulating amino acid metabolism, fatty acid metabolism, and changes in metabolic pathways such as that involved in the citric cycle (TCA cycle). The presented results indicate that PEPs treatment can alleviate the obesity and hyperlipidemia caused by a high-fat diet and, thus, may be used as a functional food adjuvant, providing a theoretical basis and technical guidance for the prevention and treatment of high-fat diet-induced obesity and hyperlipidemia.

Methanolic extract of S. securidaca flowers, leaves, and seeds' antihyperlipidemic effects on high fat diet-induced hyperlipidemia in Wistar rats.

Significant risk factors for atherosclerosis include hyperlipidemia and oxidative stress, which together rank as three of the most significant risk factors for cardiovascular diseases. Securigera securidaca lowers cholesterol levels in diabetic rats' blood. This investigation's objective was to determine how methanolic extracts affected the flowers, leaves, and seeds of plants in rats that were fed a high-fat diet (HFD). Five groups of animals were created (n = 5). A total of 35 days, divided into two intervals, were used for the study. Rats received HFD during the first 15-day interval, while during the second 20-day interval, they also received extracts or the Atorvastatin reference drug. The extract of seeds has a high phenol content as well as DPPH radical antioxidant activity. Extracts were given at a dose of 200 mg/kg; p.o. Methanolic treatment of S. securidaca flowers, leaves, and seeds in HFD-induced hyperlipidemic rats resulted in significant reductions in total cholesterol, triglycerides, LDLC, and VLDL-C levels. HDL-C levels increased significantly because of the leaves. While in hyperlipidemic rats, seeds significantly reduced the activities of the enzymes ALT and ALP. The findings showed that, to a certain extent, seeds, flowers, and leaves may have benefits in reducing hyperlipidemia brought on by HFD in terms of lipid profiles and liver function enzymes. The findings of this study indicate a promising application prospect, but more research is needed to determine the exact mechanism of these novel compounds as antihyperlipidemic agents and to clarify their potential combination effect with synthetic drugs such as Atorvastatin. Combinations can reduce the dose of chemical medications required, which lowers the risk of side effects.

Comparison of protective effects of hesperetin and pectolinarigenin on high-fat diet-induced hyperlipidemia and hepatic steatosis in Golden Syrian hamsters.

A comparative study was conducted to determine whether hesperetin and pectolinarigenin could lower total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) in a high-fat diet (HFD)-induced high lipid model in Golden Syrian hamsters. 48 Golden Syrian hamsters (8 weeks old) were fed with a HFD for 15 days. HFD induced significant increases in plasma TC, TG, LDL, and HDL. Then, these high lipid hamsters were divided into four groups and were administered with 0.5% sodium carboxymethyl cellulose (CMC-Na), hesperetin (100 mg/kg/day), pectolinarigenin (100 mg/kg/day) or atorvastatin (1.0 mg/kg/day), for 7 weeks. It was found that pectolinarigenin treatment resulted in significant reductions in body weight, adiposity index, serum levels of TC, TG and hepatic TC, TG and free fatty acid compared to those in control hamsters with hyperlipidemia (P<0.05). However, hesperetin treatment only caused reductions in plasma TC and hepatic TG levels. Besides, the hamsters treated with pectolinarigenin showed a relatively normal hepatic architecture compared to the hepatic steatosis shown in the control group. Moreover, the expressions of fatty-acid synthase (Fasn) and solute carrier family 27 member 1 (Slc27a1) involved in lipid biosynthesis, were suppressed in the pectolinarigenin-treated groups, and the expression of carnitine palmitoyltransferase 1A (Cpt1a) involved in fatty acid oxidation was increased in the pectolinarigenin-treated group. Taken together, these results suggest pectolinarigenin exerts stronger protective effects against hyperlipidemia and hepatic steatosis than hesperetin, which may involve the inhibition of lipid uptake and biosynthesis.

Transcriptomics integrated with metabolomics reveals the ameliorating effect of mussel-derived plasmalogens on high-fat diet-induced hyperlipidemia in zebrafish.

Plasmalogens (Pls), a special group of phospholipids, are effective in ameliorating neurodegenerative disease. In the present study, the metabolic effects of seafood-derived Pls on high fat diet (HFD)-induced hyperlipidemia in zebrafish were evaluated, and the underlying mechanisms of dietary Pls against hyperlipidemia were explored through integrated analyses of hepatic transcriptomics and metabolomics. The results demonstrated that Pls supplementation could effectively alleviate HFD-induced obesity symptoms, such as body weight gain, and decrease total hepatic cholesterol and triglyceride levels. Integrated hepatic transcriptome and metabolome data suggested that Pls mainly altered lipid metabolism pathways (FA metabolism, primary bile acid biosynthesis, steroid hormone biosynthesis, and glycerolipid and glycerophospholipid metabolism) and the TCA cycle, induced the overexpression of anti-oxidation enzymes (Cat, Gpx4, Sod3a and Xdh), reduced disease biomarkers (such as glutarylcarnitine, gamma-glutamyltyrosine, and 11-prostaglandin f2) and gut microbiota-derived metabolites, and increased (±)12(13)-diHOME, EPA, lysoPC and PC levels. Moreover, 5 abnormally regulated metabolites were identified as potential biomarkers associated with hyperlipidemia according to the metabolomics results and suggested the involvement of gut microbiota in the anti-hyperlipidemic effects of Pls. Collectively, these findings suggest that the protective role of Pls is mainly associated with the promotion of unsaturated fatty acid biosynthesis and cholesterol efflux, lipid and phospholipid PUFA remodeling, and anti-oxidation and anti-inflammatory capabilities. This study provides valuable information for reasonably explaining the beneficial effects of seafood-derived Pls in alleviating hyperlipidemia and thus may contribute to the development and application of Pls as functional foods or dietary supplements to protect against obesity and hyperlipidemia.

Wogonoside improves high-fat diet-induced hyperlipidemia and aortic injury in ApoE -/- mice by upregulating SIRT1 expression

This study aimed to evaluate the effect of Wogonoside (Wog), a flavonoid monomer, on hyperlipidemia and explore its possible mechanisms. APOE -/- mice were used to establish the animal model of hyperlipidemia by feeding the high-fat diet (HFD). The serum level of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA), oil red O staining, and real-time PCR assay. The oxidative stress was measured by ELISA assay. Immunoblot assay and ELISA assay were used to detect the mechanism of Wogonoside on hyperlipidemia. We found that Wogonoside ameliorated lipid metabolism disorders in ApoE -/- mice induced by HFD (P&lt;0.01). Wogonoside also ameliorated HFD-induced inflammation in ApoE -/- mice (P&lt;0.01). Wogonoside ameliorated oxidative stress in HFD-induced ApoE -/- mice (P&lt;0.01). Further study showed that Wogonoside improved HFD-induced hyperlipidemia and inflammation by upregulating SIRT1 expression (P&lt;0.01). These results suggested that Wogonoside has the potential to be used as a promising approach for the intervention of hyperlipidemia.

Ponatinib modulates the metabolic profile of obese mice by inhibiting adipose tissue macrophage inflammation.

Obesity-induced metabolic syndrome is a rapidly growing conundrum, reaching epidemic proportions globally. Chronic inflammation in obese adipose tissue plays a key role in metabolic syndrome with a series of local and systemic effects such as inflammatory cell infiltration and inflammatory cytokine secretion. Adipose tissue macrophages (ATM), as one of the main regulators in this process, are particularly crucial for pharmacological studies on obesity-related metabolic syndrome. Ponatinib, a multi-targeted tyrosine kinase inhibitor originally used to treat leukemia, has recently been found to improve dyslipidemia and atherosclerosis, suggesting that it may have profound effect on metabolic syndrome, although the mechanisms underlying have not yet been revealed. Here we discovered that ponatinib significantly improved insulin sensitivity in leptin deficient obese mice. In addition to that, ponatinib treatment remarkably ameliorated high fat diet-induced hyperlipidemia and inhibited ectopic lipid deposition in the liver. Interestingly, although ponatinib did not reduce but increase the weight of white adipose tissue (WAT), it remarkably suppressed the inflammatory response in WAT and preserved its function. Mechanistically, we showed that ponatinib had no direct effect on hepatocyte or adipocyte but attenuated free fatty acid (FFA) induced macrophage transformation from pro-inflammatory to anti-inflammatory phenotype. Moreover, adipocytes co-cultured with FFA-treated macrophages exhibited insulin resistance, while pre-treat these macrophages with ponatinib can ameliorate this process. These results suggested that the beneficial effects of ponatinib on metabolic disorders are achieved by inhibiting the inflammatory phenotypic transformation of ATMs, thereby maintaining the physiological function of adipose tissue under excessive obesity. The data here not only revealed the novel therapeutic function of ponatinib, but also provided a theoretical basis for the application of multi-target tyrosine kinase inhibitors in metabolic diseases.

Loss of GPR40 in LDL receptor-deficient mice exacerbates high-fat diet-induced hyperlipidemia and nonalcoholic steatohepatitis.

GPR40, a G protein-coupled receptor for free fatty acids (FFAs), is considered as a therapeutic target for type 2 diabetes mellitus (T2DM) since GPR40 activation in pancreatic beta cells enhances glucose-stimulated insulin secretion. Nonalcoholic fatty liver disease (NAFLD) is a common complication of T2DM or metabolic syndrome (MetS). However, the role of GPR40 in NAFLD associated with T2DM or MetS has not been well established. Given that it is known that cholesterol and FFAs are critically involved in the pathogenesis of nonalcoholic steatohepatitis (NASH) and LDL receptor (LDLR)-deficient mice are a good animal model for human hyperlipidemia including high cholesterol and FFAs, we generated GPR40 and LDLR double knockout (KO) mice in this study to determine the effect of GPR40 KO on hyperlipidemia-promoted NASH. We showed that GPR40 KO increased plasma levels of cholesterol and FFAs in high-fat diet (HFD)-fed LDLR-deficient mice. We also showed that GPR40 KO exacerbated HFD-induced hepatic steatosis, inflammation and fibrosis. Further study demonstrated that GPR40 KO led to upregulation of hepatic CD36 and genes involved in lipogenesis, fatty acid oxidation, fibrosis and inflammation. Finally, our in vitro mechanistic studies showed that while CD36 was involved in upregulation of proinflammatory molecules in macrophages by palmitic acid (PA) and lipopolysaccharide (LPS), GPR40 activation in macrophages exerts anti-inflammatory effects. Taken together, this study demonstrated for the first time that loss of GPR40 in LDLR-deficient mice exacerbated HFD-induced hyperlipidemia, hepatic steatosis, inflammation and fibrosis potentially through a CD36-dependent mechanism, suggesting that GPR40 may play a beneficial role in hyperlipidemia-associated NASH in LDLR-deficient mice.

Amino Acid Conjugates of 2-Mercaptobenzimidazole Ameliorates High-Fat Diet-Induced Hyperlipidemia in Rats via Attenuation of HMGCR, APOB, and PCSK9

This study was designed to explore the antihyperlipidemic effects of amino acid derivatives of 2-mercaptobenzimidazole (4J and 4K) in high-fat diet (HFD)-fed rats. Male Sprague-Dawley rats were divided into nine groups which received either standard diet or HFD for 28 days. Blood samples were taken on 27th day from HFD-fed rats to ensure hyperlipidemia. HFD-induced hyperlipidemic rats later received daily dosing of either vehicle or simvastatin (SIM; 20 mg/kg) or 4J/4K compounds (10, 20, and 30 mg/kg) for 12 consecutive days. On 40th day, animals were sacrificed, and blood samples were collected for the determination of serum lipid profile and liver function parameters. Liver samples were harvested for histopathological, antioxidant, and qPCR analyses. Molecular docking of tested compounds with HMGCR was also performed to assess the binding affinities. 4J and 4K dose dependently decreased serum total cholesterol, triglycerides, low-density lipoprotein, very low-density lipoproteins, alanine transaminase (ALT), and aspartate aminotransferase (AST) levels while significantly alleviated high-density lipoproteins. However, SIM failed to reduce AST and ALT levels. Moreover, tested compounds displayed antioxidant effects by inducing superoxide dismutase and glutathione levels. Histopathology data also displayed protective effects of 4J and 4K against HFD-induced fatty changes and hepatic damage. In addition, 4J and 4K downregulated transcript levels of HMGCR, APOB, PCSK9, and VCAM1, and molecular docking analysis also supported the experimental data. It is conceivable from this study that 4J and 4K exert their antihyperlipidemic effects by modulating multiple targets regulating lipid levels.

Evaluation of Antihyperlipidemic Activity of Choerospondias axillaris in Rats

Background: Choerospondias axillaris CA, known as lapsi, is a plant with constituents having therapeutic properties. All plant parts including stem, bark, root, leaves, and fruit have medicinal virtues and have had a role in Ethno-medicine since ancient times.&#x0D; Objective: The present study was designed to investigate the antihyperlipidemic activity of dried powder of Choerospondias axillaris fruits in Wistar albino rats.&#x0D; Methods: The anti-hyperlipidemic effect of methanolic extract of the fruit of Choerospondias axillaris (CA) was tested in a high-fat diet-induced hyperlipidemic rat model. Here, chronic hyperlipidemia was induced by feeding a high-fat diet for 21 days to rats. During the experiment, the rat’s body weight was monitored. At the end of the study, animals among whole groups have been sacrificed and biochemical parameters such as; serum Total Cholesterol, Triglycerides, Low-Density Lipoprotein Cholesterol (LDL-C), Very Low-Density Lipoprotein Cholesterol (VLDL-C), and increase of serum High-Density Lipoprotein Cholesterol (HDL-C) were analysed.&#x0D; Results: The observed extract of Choerospondias axillaris was proven to be safe in the toxicity findings. Treatment with methanolic extract of CA (200 and 400 mg/kg, p.o) significantly reduced the hyperlipidemia i.e., the decline in levels of serum Total Cholesterol, Triglycerides, Low-Density Lipoprotein Cholesterol (LDL-C), Very Low-Density Lipoprotein Cholesterol (VLDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) when compared to vehicle control and standard drug Atorvastatin (10 mg/kg). The result indicates that methanolic extract of the whole plant of Choerospondias axillaris possessed significant antihyperlipidemic activity.&#x0D; Conclusion: After all the investigation it was found that oral administration of Choerospondias axillaris fruit extract at a low dose of 300mg/kg and a high dose of 600mg/kg against the high-fat diet-induced hyperlipidemia and it was found that a high dose was more effective as compared to low dose. The drug was able to suppress the raised parameters.

Gryllus bimaculatus extract ameliorates high-fat diet-induced hyperglycemia and hyperlipidemia by inhibiting hepatic lipogenesis through AMPK activation.

The online version contains supplementary material available at 10.1007/s10068-022-01117-9.

Functional yogurt fermented by two-probiotics regulates blood lipid and weight in a high-fat diet mouse model.

We investigated the blood lipid regulation effects and mechanism of a functional Natto yogurt in a high-fat diet-induced hyperlipidemia mouse model. Natto yogurt was characteristically fermented by Bacillus natto and Lactobacillus plantarum with milk-soy dual protein as substrates. After 5 weeks of Natto yogurt consumption, the body weight, fat, and liver weight of mice were significantly improved, while serum levels of TG, TC, LDL, ALT, TBIL, and TBA were reduced. Natto yogurt significantly decreased the area of liver fat infiltration and the number of lipid droplets. In mechanism, we found that Natto yogurt can inhibit fatty acid synthesis and enhance fatty acid catabolism by regulating the expression of PPARα, PPARγ, CD36 and FAS in the liver. Moreover, Natto yogurt increased the ratio of Bacteroidetes to Firmicutes in the intestine. These results provide a possibility for Natto yogurt as a dual protein functional food to prevent and treat hyperlipidemia and obesity. PRACTICAL APPLICATIONS: Traditional-fermented yogurt promotes nutritional absorption and reduces blood pressure and fat, while Bacillus natto and its fermented food have been proved to play a significant role in improving cardiovascular and cerebrovascular diseases and obesity. Therefore, we developed a new dual protein functional yogurt (Natto yogurt) fermented by B. natto and Lactobacillus plantarum with milk and soy as substrates. We found that Natto yogurt could notably regulate blood lipid by inhibiting the synthesis of fatty acids, accelerating the catabolism of fatty acids, reducing liver damage, and increasing the abundance of beneficial intestinal microorganisms. This study suggested that Natto yogurt could improve hyperlipidemia and obesity as a safe, effective, and healthy functional food.

Fermented Rosa Roxburghii Tratt Juice Alleviates High-Fat Diet-Induced Hyperlipidemia in Rats by Modulating Gut Microbiota and Metabolites.

Hyperlipidemia endangers human health and has become a significant public health problem. This study aimed to investigate the mechanism of the hypolipidemic effects of Fermented Rosa roxburghii Tratt juice (FRRT) on hyperlipidemic rats and a new hypolipidemic intervention strategy was disclosed. The study revealed 12 weeks FRRT treatment significantly decreased the body weight, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-c), while high-density lipoprotein cholesterol (HDL-c) increased. We integrated the 16S rDNA sequencing and metabolomic profiling to evaluate the changes in the gut microbiota and metabolites. Significant changes in microbial composition accompanied marked changes in 56 feces metabolites. The results showed that FRRT could decrease the ratio of Firmicutes to Bacteroidetes, while increase the abundance of some bacterial genera (Prevotella, Paraprevotellaceae_Prevotella, Ruminococcus, Oscillospira). Metabolomics analysis displayed that the metabolisms of bile acid, amino acid and lipid were significantly affected by FRRT. Correlation analysis suggest that the reductions in serum lipids by FRRT are associated with the gut microbial community and their associated metabolites (amino acid metabolites, bile acid metabolites, and lipid metabolites). This study confirmed FRRT could be used as a new dietary and therapeutic strategy to dyslipidemia by improving the gut microbiota dysbiosis, metabolomic disorders and regulating the dyslipidemia. Our study also extended the understanding of the relationship between gut microbiota, metabolites, and lipid-lowering functions.

Oryzanol Attenuates High Fat and Cholesterol Diet-Induced Hyperlipidemia by Regulating the Gut Microbiome and Amino Acid Metabolism.

Hyperlipidemia is intricately associated with the dysregulation of gut microbiota and host metabolomes. This study explored the antihyperlipidemic function of oryzanol and investigated whether the function of oryzanol affected the gut microbiome and its related metabolites. Hamsters were fed a standard diet (Control) and a high fat and cholesterol (HFCD) diet with or without oryzanol, separately. Our results showed that oryzanol significantly decreased HFCD-induced fat accumulation, serum total cholesterol, low-density lipoprotein cholesterol (LDL-c), LDL-c/HDL-c ratio, triglyceride, and liver steatohepatitis, attenuated HFCD-induced gut microbiota alterations, and altered amino acid concentrations in feces and the liver. We investigated the role of the gut microbiota in the observed beneficial effects; the protective effects of oryzanol were partly diminished by suppressing the gut bacteria of hamsters after using antibiotics. A fecal microbiota transplantation experiment was carried out by transplanting the feces from HFCD group hamsters or hamsters given oryzanol supplementation (as a donor hamster). Our results showed that administering the fecal liquid from oryzanol-treated hamsters attenuated HFCD-induced hyperlipidemia, significantly decreased the abundance of norank_f__Erysipelotrichaceae, norank_f__Eubacteriaceae, and norank_f__Oscillospiraceae and the concentration of tyrosine. These outcomes are significantly positively correlated with serum lipid concentration. This study illustrated that gut microbiota is the target of oryzanol in the antihyperlipidemic effect.

Probiotic-fermented rice buckwheat alleviates high-fat diet-induced hyperlipidemia in mice by suppressing lipid accumulation and modulating gut microbiota

Hyperlipidemia is associated with lipid metabolic disorders, chronic inflammation, and intestinal dysbiosis. Previous studies have shown that the metabolic improvement of high-fat diet (HFD)-induced mice by buckwheat is correlated with gut microbiota; however, the anti-hyperlipidemia effects and potential mechanism of probiotics-fermented rice buckwheat (FRB) are not well understood. Here, we aimed to investigate the lipid-lowering and gut microbiota regulation of FRB in HFD-induced hyperlipidemic mice. We observed that probiotic fermentation markedly increased the contents of γ-aminobutyric acid, rutin, total polyphenols, and total flavonoids in rice buckwheat. FRB supplementation over eight weeks significantly reduced body weight gain and visceral obesity, as well as alleviating dyslipidemia in HFD-fed mice. Moreover, FRB treatment effectively ameliorated oxidative stress and chronic inflammation. We further demonstrated that FRB intervention significantly inhibited hepatic cholesterol synthesis and lipogenesis, and promoted lipolysis. More important, FRB treatment reversed HFD-induced gut dysbiosis by decreasing the ratio of Firmicutes to Bacteroidetes and increasing the abundance of SCFA-producing bacteria such as Bacteroides, Lactobacillus, and Blautia, along with increasing the total SCFAs contents. Overall, these results show that FRB is a beneficial nutraceutical for hyperlipidemia amelioration.

Study of Association between Serum Hepsin Level and Lymphocyte-to-C-reactive Protein Ratio in Patients with Diabetes

Background: Hepsin is known as a cell-surface serine protease expressed predominantly in the liver. Hepsin-deficient mice show resistance to high-fat diet-induced obesity, hyperlipidemia, and hyperglycemia. Up to the present, the physiological function of hepsin has not been fully determined. Hepsin may play significant and specific roles in diabetes. Objectives: This study aimed to evaluate the relationship between hepsin protein concentrations in serum and type 2 diabetes mellitus (T2DM) and elucidate possible associations with disease activity andinflammatory and metabolic parameters. To the best of our knowledge, this is the first study evaluating the relationship between hepsin, lymphocyte-to-C-reactive protein ratio (LCR), and type 2 diabetes in humans in the existingliterature. Methods: This case-control study included 60 patients (30 males and 30 females) diagnosed with type 2 diabetes, according to American Diabetes Association's criteria, and 30 healthy controls (14 males and 16 females) with similar demographic characteristics. Several laboratory parameters were assessed including fasting glucose, total cholesterol, insulin, hemoglobin A1c, gamma-glutamyl transferase, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid, C-reactive protein, atherogenic index of plasma, LCR, monocyte-to-neutrophil ratio,neutrophil-to-lymphocyte ratio, and serum hepsin levels. Results: The type 2 diabetes group had significantly higher LCR than controls (P&lt;0.016). Correlation analysis in the patient group showed a statistically significant relationship between hepsin and LCR (rho=0.296,P=0.02). Hepsin was negatively correlated with CRP in the patient group (rho=-0.333, P=0.01). Correlation analysis in the patient group showed a statistically significant relationship between hepsin and cholesterol (rho= 0.29,P= 0.02). Age was positively correlated with hepsin in the patient group (rho= 0.267, P=0.04). There was no statistically significant difference in serum hepsin levels between the diabetes group and the control group (P=0.157). Conclusion: To the best of our knowledge, this is the first study assessing the hepsin levels in patients with T2DM. Our results indicated that increased levels of hepsin could be associated with the inflammatory processes. Similar results were not found for diabetes. However, it is recommended that similar studies should be conducted in larger patient populations.

Deep Sea Water-Dissolved Organic Matter Intake Improves Hyperlipidemia and Inhibits Thrombus Formation and Vascular Inflammation in High-Fat Diet Hamsters.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by oxidative stress, inflammation and lipid deposition within liver cells, and is subsequently contributing to cardiovascular diseases such as atherosclerosis. Deep sea water (DSW) is characterized by its clearance and abundant nutrients with antioxidant and anti-inflammatory activity to confer therapeutic potential. We aimed to explore the therapeutic capability of our prepared multi-filtration DSW-dissolved organic matter (DSW-DOM) on high-fat diet-induced hyperlipidemia and endothelial dysfunction in hamsters. A high-fat/high-cholesterol diet led to increased oxidative stress, including blood reactive oxygen species (ROS), plasma malondialdehyde (MDA) and hepatic CYP2E1 expression; an increased hyperlipidemic profile and SREBP 1-mediated fatty liver; promoted NFκB p65-mediated hepatic inflammation; triggered PARP-mediated hepatic apoptosis; and enhanced endothelial intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor (VWF)-mediated atherosclerosis associated with the depressed hepatic antioxidant Paraoxonase 1 (PON1) expression. The DSW-DOM-enriched 1295 fraction, with strong H2O2 scavenging activity, efficiently reduced several oxidative stress parameters, the lipid profile, inflammation, and apoptosis, possibly through the PON1-mediated antioxidant capability. Furthermore, DSW-DOM treatment significantly decreased the endothelial ICAM-1 and VWF expression, subsequently leading to the elongation of time to occlusion of FeCl3-induced arterial thrombosis and to the inhibition of FeCl3-induced fluorescent platelet adhesion to mesentery arterioles in the high-fat diet. Based on the above results, our data suggest that DSW-DOM intake via antioxidant defense mechanisms confers protective effects against high-fat diet-enhanced, oxidative stress-mediated hyperlipidemia, and endothelial dysfunction evoked atherosclerosis by downregulating oxidative injury, lipogenesis, inflammation and apoptosis.

Protective effect of microorganism biotransformation-produced resveratrol on the high fat diet-induced hyperlipidemia, hepatic steatosis and synaptic impairment in hamsters.

Background: Resveratrol, a natural antioxidant polyphenol, has the functions of anti-inflammation, anti-cancer, liver protection and cardioprotection. Microorganism biotransformation-produced resveratrol (MBR) product shows higher purity than the natural source of resveratrol and costs less than the chemically synthesized resveratrol. The aim of the present study was to investigate the protective effects of MBR in hamsters treated with a high-fat diet (HFD).Methods: MBR was obtained by the fermentative process of piceid. Hamsters were randomly divided into four groups: HFD plus oral administration of MBR 0 (C), 5 (L), 20 (M) or 50 mg/kg (H), respectively. After six-week of treatment, hamsters were sacrificed, and tissues were collected for further analysis.Results: MBR at these three dosages did not influence the appetite or growth of the hamsters. Liver enzymes, blood glucose, total cholesterol, triglyceride, and liver weight were significantly reduced in the MBR groups than in the control group. Additionally, high-density lipoprotein-cholesterol (HDL-C) was also elevated in all MBR groups. On the other hand, serum low-density lipoprotein-cholesterol (LDL-C) was decreased in the MBR groups. Triglyceride (TG) in liver tissue and fatty liver level were lower in group H. Memory-associated proteins, phosphorylation of calmodulin-dependent protein kinase II (p-CaMK II) and synaptophysin (SYP), were increased in the brains of MBR groups.Conclusion: The high yield- and short procedure-produced MBR has the potential to protect animals fed with HFD from hyperlipidemia, hepatic steatosis, hyperglycemia, and synaptic impairment, which might be beneficial for patients with these types of diseases.

The potential mechanisms of bergamot-derived dietary fiber alleviating high-fat diet-induced hyperlipidemia and obesity in rats.

This study is aimed to investigate the health-associated benefits of bergamot-dietary fibers (DFs) with a special emphasis on weight loss and lipid-lowering effects, as well as the potential mechanisms involved. The feeding experiment of Sprague-Dawley (SD) rats for 6 weeks showed that DFs had dose-dependent regulatory effects against metabolic syndrome and they controlled obesity by slowing down the rate of weight growth, and reduced body mass index (BMI) and Lee's index without affecting appetite. Furthermore, DFs inhibited increment in TG, TC, LDL-C levels and AI index caused by a high-fat diet, and improved the pathological abnormality of the liver. Western blot results showed that DFs significantly up-regulated the protein expression levels of LXRα and CYP7A1, and down-regulated the levels of SREBP-1c, FAS, ACC and SREBP-2 in the liver. QRT-PCR results showed that DFs up-regulated PGC-1α, PRDM16, UCP-1, and PPARγ in brown adipose tissue. These results suggest that DFs played an effective role in reducing weight and lipids levels by promoting the decomposition and transport of lipids in liver, increasing the energy consumption of brown adipose tissue. DFs intervention reduced the difference in the intestinal microflora between rats fed with a normal diet and those fed with a high-fat diet. Soluble dietary fiber (SDF) and total dietary fiber (TDF) showed better weight loss and hypolipidemic potential compared to insoluble dietary fiber (IDF) at the same dose. In conclusion, bergamot-derived DFs demonstrated the potential to lower blood cholesterol and body weight and could be used to develop novel functional foods for the prevention or treatment of obesity and hyperlipidemia.

Antihyperlipidemic and Antiobesity Potential of Aquilaria agallocha and Borago officinalis in Fixed-Dose Combination; A Contingent Probe with Atorvastatin and Orlistat

Aims: Antihyperlipidemic and antiobesity potential of a fixed dose combination of Aquilaria agallocha &amp; Borago officinalis along with its comparative evaluation with Atorvastatin &amp; Orlistat. Background: Hyperlipidemia and obesity are common and challenging health problems throughout the world. These are the conditions in which increased lipids level in blood are the risk factors for atherosclerosis, coronary artery disease, and cerebral vascular diseases. In the present study, the fixed-dose combination of absolute ethanolic extract of Aquilaria agallocha and aqueous extract of Borago officinalis was examined for its antihyperlipidemic effect and antiobesity activity in the Sprague Dawley rats. Objective: A suitable &amp; established experimental model of hyperlipidemia and obesity based on literature survey has been selected. Comparative evaluation of fixed dose combination with selected standard drug against the established model. Compilation of results and statistical analysis. Methods: Drugs and Chemicals: Atorvastatin solution, Orlistat solution, Formalin solution Animals: sprague dawley rats of 150-200 g of either sex were used for the study. Animals were habituated to laboratory conditions for 48 hours prior to experimental protocol to minimize if any of nonspecific stress. All the studies conducted were approve by the Institutional Animal Ethical Committee (IAEC) of Faculty of Pharmacy, Integral University Lucknow (Reg. no. 1213/PO/Re/S/08/CPCSEA, 5th June 2008) having approval no. IU/IAEC/18/32. High fat diet induced Dyslipidemia and obesity: Baseline characteristics of obesity and hyperlipedimia induced by high fat diet in Sprague dawley rats were maintained on normal pellet diet (NPD) for one week before the commencement of experiment. After one week rats were randomly assigned into normal and obese group and fed with NPD and High fat diet and libitum respectively for one week.The food intake, body weight gain ,and lipid profile were carried out on day 8 of dietary manipulation to assess the baseline characteristics of obesity and hyperlipidemia induced by high fat diet in Sprague dawley rats. Results: The result of the study shows that the ethanolic extract of the FDC of aquilaria agallocha &amp; borago officinalis has significant anti-hyperlipidemic and anti-obesity activity against High- fat diet-induced hyperlipidemia and obesity compared to atorvastatin (10 mg/kg) and orlistat (pure drug 10mg/kg). Conclusion: The present study shows that pretreatment with ethanolic extract of FDC of Aquilaria agallocha &amp; Borago officinalis significantly prevented from hyperlipidemia and obesity and decreased the levels of diagnostic marker enzymes significantly. At low dose (Borago officinalis 100 mg/kg + Aquilaria agallocha 250 mg/kg b.w.) ) ethanolic extract of FDC of Aquilaria agallocha &amp; Borago officinalis showed moderate protection against Hyperlipidemia and Obesity. At high dose (Borago officinalis 200 mg/kg + Aquilaria agallocha 500 mg/kg b.w.) ethanolic extract of FDC of Aquilaria agallocha &amp; Borago officinalis showed marked protection against High fat diet induced hyperlipidemia and obesity as well as by biochemical estimations of Lipid profile compare to the standard Atorvastatin(10mg/kg) and Orlistat(10mg/kg). Thus it concludes that ethanolic extract of FDC of Aquilaria agallocha &amp; Borago officinalis possesses potent against high fat diet induced hyperlipidemia and obesity.

The zinc finger and BTB domain containing protein ZBTB20 regulates plasma triglyceride metabolism by repressing lipoprotein lipase gene transcription in hepatocytes.

Lipoprotein lipase (LPL) is responsible for the lipolytic processing of triglyceride-rich lipoproteins, the deficiency of which causes severe hypertriglyceridemia. Liver LPL expression is high in suckling rodents but relatively low at adulthood. However, the regulatory mechanism and functional significance of liver LPL expression are incompletely understood. We have established the zinc finger protein ZBTB20 as a critical factor for hepatic lipogenesis. Here, we evaluated the role of ZBTB20 in regulating liver Lpl gene transcription and plasma triglyceride metabolism. Hepatocyte-specific inactivation of ZBTB20 in mice led to a remarkable increase in LPL expression at the mRNA and protein levels in adult liver, in which LPL protein was mainly localized onto sinusoidal epithelial cells and Kupffer cells. As a result, the LPL activity in postheparin plasma was substantially increased, and postprandial plasma triglyceride clearance was significantly enhanced, whereas plasma triglyceride levels were decreased. The dysregulated liver LPL expression and low plasma triglyceride levels in ZBTB20-deficient mice were normalized by inactivating hepatic LPL expression. ZBTB20 deficiency protected the mice against high-fat diet-induced hyperlipidemia without causing excessive triglyceride accumulation in the liver. Chromatin immunoprecipitation and gel-shift assay studies revealed that ZBTB20 binds to the LPL promoter in the liver. A luciferase reporter assay revealed that ZBTB20 inhibits the transcriptional activity of LPL promoter. The regulation of LPL expression by ZBTB20 is liver-specific under physiological conditions. Liver ZBTB20 serves as a key regulator of LPL expression and plasma triglyceride metabolism and could be a therapeutic target for hypertriglyceridemia.