High-fat Diet-induced Rats Research Articles

Correlation between Intermittent Fasting and Mental and Physical Fatigue in High‐fat‐induced Obese and Non‐obese Rats

Intermittent fasting (IF) is an alternate pattern of eating and restricting food intake. This study evaluated mental and physical fatigue secondary to IF in high‐fat diet‐induced (HFD) obese male rats. Fifty‐four rats were randomly assigned to a HFD (n=28) or a standard diet (SD; n=26). After six weeks, the HFD rats were divided into one of four groups: obese HFD ad libitum (OB‐HFD‐AL), obese HFD intermittent fasting (OB‐HFD‐IF), obese SD ad libitium (OB‐SD‐AL), and obese SD IF (OB‐SD‐IF). Similarly, non‐obese controls were grouped into HFD ad libitum (C‐HFD‐AL), non‐obese HFD IF (C‐HFD‐IF), non‐obese SD ad libitum (C‐SD‐AL), and non‐obese SD IF (C‐SD‐IF). The IF groups fasted for 18 hours per day, seven days a week. After two weeks, their physical and mental fatigue was measured using open field (OF) and novel object recognition (NOR) paradigms. Regardless of the diet type, rats on IF gained weight at a slower pace (p< 0.05) and had lower glucose levels (p < 0.01) compared to the AL group. In non‐obese rats, ketone levels were higher in the IF‐HFD group compared to the IF‐SD (p<0.05) and AL‐SD (p<0.01) groups. Obese rats exhibited higher ketones in IF‐SD conditions versus AL‐SD rats (p<0.01). In both obese and non‐obese groups, AL‐HFD rats had higher ketone levels than AL‐SD rats (p<0.05). Increased ketone levels could be correlated with greater distance traveled during OF. IF protected against recognition memory deficit during NOR. Overall, this study demonstrates that increased ketone levels, whether caused by diet type or IF, correlate to decreased physical fatigue and protect against mental fatigue.

Polygonatum sibiricum polysaccharides protect against obesity and non-alcoholic fatty liver disease in rats fed a high-fat diet

Polygonatum sibiricum is a traditional medicinal and dietary plant of the family Liliaceae. The main functional macromolecules of P. sibiricum are polysaccharides, which function in antioxidation and regulating immunity. Previous studies have shown that insulin resistance (IR), oxidative stress, and inflammation are important factors in the induction of lipid metabolic diseases such as obesity. Therefore, in this study, we established a high-fat diet-induced rat model of obesity and nonalcoholic fatty liver disease (NAFLD) to explore the potential protective effect of P. sibiricum polysaccharides (PSPs) and the mechanisms behind it. After 4 weeks of high-fat diet feeding to induce obesity, the rats were treated with different doses of PSP solution or distilled water for 6 weeks. Compared with untreated obese rats, PSP-treated obese rats showed a decrease in body weight, serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, hepatic aspartate aminotransferase and alanine aminotransferase activity, hepatic malondialdehyde content, and hepatic levels of the pro-inflammatory factors tumor necrosis factor-α, interleukin-1β, and interleukin-6, as well as increased serum high-density lipoprotein cholesterol levels and hepatic superoxide dismutase, catalase, and glutathione peroxidase activity. Pathological analysis and immunoblotting of the liver tissues indicated that mechanistically, PSPs reduced obesity and NAFLD in rats by upregulating insulin receptor expression, increasing adenosine monophosphate-activated protein kinase phosphorylation, and downregulating sterol regulatory element-binding protein 2 and low-density lipoprotein receptor expression, thus promoting lipid metabolism, decreasing body weight, and reducing inflammation and oxidative stress caused by lipid accumulation. Based on these results, PSPs may have the potential to reduce obesity and NAFLD associated with a high-fat diet.

The Hypolipidemic and Antioxidant Activity of Wheat Germ and Wheat Germ Protein in High-Fat Diet-Induced Rats.

Background: So far, no articles have discussed the hypolipidemic effect of wheat germ protein in in vivo experiments. Objective: In this study, we investigated the effects of wheat germ protein (WGP, 300 mg/kg/day) and wheat germ (WG, 300 mg/kg/day) on cholesterol metabolism, antioxidant activities, and serum and hepatic lipids in rats fed a high-fat diet through gavage. Methodology: We used 4-week-old male Wistar 20 rats in our animal experiment. Biochemical indicators of fecal, serum and liver were tested by kits or chemical methods. We also conducted the cholesterol micellar solubility experiment in vitro. Results: After 28 days of treatment, our results showed that WGP significantly reduced the serum levels of total cholesterol (p < 0.05) and nonhigh-density lipoprotein cholesterol (p < 0.05), improved the enzymatic activities of cholesterol 7-α hydroxylase (p < 0.01) and low-density lipoprotein receptor (p < 0.01) and increased bile acid excretion in feces (p < 0.05). Conclusion: WG did not significantly increase bile acid excretion in feces or decrease serum levels of total cholesterol. Moreover, WGP and WG both presented significant antioxidant activity in vivo (p < 0.05) and caused a significant reduction in cholesterol micellar solubility in vitro (p < 0.001). Therefore, WGP may effectively prevent hyperlipidemia and its complications as WGP treatment enhanced antioxidant activity, decreased the concentration of serum lipids and improved the activity of enzymes involved in cholesterol metabolism.

Network pharmacology analysis to explore mechanism of Three Flower Tea against nonalcoholic fatty liver disease with experimental support using high-fat diet-induced rats

ObjectiveNonalcoholic fatty liver disease (NAFLD) has become a common chronic liver disease that is harmful to human health. Moreover, there is currently no FDA-approved first-line drug for the treatment of nonalcoholic steatohepatitis (NASH) or NAFLD. Traditional Chinese medicine (TCM) is widely used to ameliorate liver diseases, such as the traditional ancient recipe called Three Flower Tea (TFT), which consists of double rose (Rosa rugosa), white chrysanthemum (Chrysanthemum morifolium), and Daidaihua (Citrus aurantium). However, the mechanisms of the action of TFT are not clear. Therefore, this study aimed to elucidate the mechanisms of TFT against NAFLD in high-fat diet (HFD)-induced rats. MethodsThis study utilized bioinformatics and network pharmacology to establish the active and potential ingredient-target networks of TFT. Furthermore, a protein–protein interaction (PPI) network was constructed, and enrichment analysis was performed to determine the key targets of TFT against NAFLD. Furthermore, an animal experiment was conducted to evaluate the therapeutic effect and confirm the key targets of TFT against NAFLD. ResultsA total of 576 NAFLD-related genes were searched in GeneCards, and under the screening criteria of oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18, a total of 19 active ingredients and 210 targets were identified in TFT. Network pharmacology analysis suggested that 55 matching targets in PPIs were closely associated with roles for NAFLD treatment. Through the evaluation of network topology parameters, four key central genes, PPARγ, SREBP, AKT, and RELA, were identified. Furthermore, animal experiments indicated that TFT could reduce plasma lipid profiles, hepatic lipid profiles and hepatic fat accumulation, improve liver function, suppress inflammatory factors, and reduce oxidative stress. Through immunoblotting and immunofluorescence analysis, PPARγ, SREBP, AKT, and RELA were confirmed as targets of TFT in HFD-induced rats. ConclusionIn summary, our results indicate that TFT can prevent and treat NAFLD via multiple targets, including lipid accumulation, antioxidation, insulin sensitivity, and inflammation.

Kaempferol prevents the progression from simple steatosis to non-alcoholic steatohepatitis by inhibiting the NF-κB pathway in oleic acid-induced HepG2 cells and high-fat diet-induced rats

Currently, non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and more functional foods are needed for NAFLD prevention and treatment. Kaempferol can be obtained from tea, broccoli, propolis, grapefruit and other green plants. However, relatively systematic studies concerning the preventative effects of kaempferol against NAFLD are lacking. In this study, using network pharmacological methods, we found that kaempferol could prevent the development of NAFLD by targeting multiple targets; for instance, kaempferol suppressed inflammation, improved insulin resistance and reduced oxidative stress. Furthermore, we confirmed that kaempferol could suppress inflammatory responses and prevent the development of NAFLD in vitro and in vivo by inhibiting the nuclear transcriptional activity of NF-κB. Our study supports the use of kaempferol as a functional food or dietary supplement for NAFLD prevention and treatment. In addition, this study could be beneficial for understanding the anti-NAFLD mechanism of many other flavonoids.

The Effectiveness of Long-term Use of Low-Molecular-Weight Heparin on Venous Thromboembolism After Sleeve Gastrectomy in Rats

Objectives: The aim of the study was to investigate the effects of bemiparin administration for 15 and 30 days on deep vein thrombosis (DVT) in high-fat diet-induced rats, followed by sleeve gastrectomy (SG) for DVT prophylaxis. Setting: The study was conducted at the Kobay Experimental Animals Laboratory. Materials and Methods: Forty rats were fed a high-fat diet to induce obesity. They were then equally divided into four groups (n = 10); group 1 (control group); group 2 (nonbemiparin group); and group 3 (15-day bemiparin group) and group 4 (30-day bemiparin group) in which bemiparin therapeutic doses were administered for 15 and 30 days, respectively. Sixteen weeks after feeding, SG was performed on rats from groups 2, 3, and 4. Doppler ultrasonography was performed to investigate thrombosis of the inferior vena cava and iliac veins in all rats before and 1 month after SG. Rat vena cava, iliac veins, and lung tissues were removed to determine venous thrombosis status and investigate microthrombi through histological examination. Results: No statistically significant difference was found between groups in terms of the thickness of intima–media (μm), thrombus area (μm2), and erythrocyte, leukocyte, and platelet/fibrin values of the iliac veins (p > 0.05). A statistically significant difference was found between groups in terms of the presence of thrombus and radiological status of the vena cava (p < 0.05). In addition, the measurement percentage was found to be 100% in group 2, 37.5% in group 3, and 12.5% in group 4. Conclusion: We believe that administration of bemiparin once a day for 30 days can be a safe and effective treatment method in the prevention of microthrombi, following SG.

Extraction and Hypolipidemic Activity of Low Molecular Weight Polysaccharides Isolated from Rosa Laevigata Fruits.

Three novel low molecular weight polysaccharides (RLP-1a, RLP-2a, and RLP-3a) with 9004, 8761, and 7571 Da were first obtained by purifying the crude polysaccharides from the fruits of a traditional Chinese medicinal herb Rosae Laevigatae. The conditions for polysaccharides from the R. Laevigatae fruit (RLP) extraction were optimized by the response surface methodology, and the optimal conditions were as follows: extraction temperature, 93°C; extraction time, 2.8 h; water to raw material ratio, 22; extraction frequency, 3. Structural characterization showed that RLP-1a consisted of rhamnose, arabinose, xylose, glucose, and galactose with the ratio of 3.14 : 8.21 : 1 : 1.37 : 4.90, whereas RLP-2a was composed of rhamnose, mannose, glucose, and galactose with the ratio of 1.70 : 1 : 93.59 : 2.73, and RLP-3a was composed of rhamnose, arabinose, xylose, mannose, glucose, and galactose with the ratio of 6.04 : 26.51 : 2.05 : 1 : 3.17 : 31.77. The NMR analyses revealed that RLP-1a, RLP-2a, and RLP-3a contained 6, 4, and 6 types of glycosidic linkages, respectively. RLP-1a and RLP-3a exhibited distinct antioxidant abilities on the superoxide anions, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and hydroxyl radicals in vitro. RLPs could decrease the serum lipid levels, elevate the serum high-density lipoprotein cholesterol levels, enhance the antioxidant enzymes levels, and upregulate of FADS2, ACOX3, and SCD-1 which involved in the lipid metabolic processes and oxidative stress in the high-fat diet-induced rats. These results suggested that RLPs ameliorated the high-fat diet- (HFD-) induced lipid metabolism disturbance in the rat liver through the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Low molecular weight polysaccharides of RLP could be served as a novel potential functional food for improving hyperlipidemia and liver oxidative stress responses.

Effect of Lactobacillus plantarum HT121 on serum lipid profile, gut microbiota, and liver transcriptome and metabolomics in a high-cholesterol diet-induced hypercholesterolemia rat model.

The aim of this study was to evaluate effect of Lactobacillus plantarum HT121 on serum lipid profile, gut microbiota, and liver transcriptome and metabolomics. L. plantarum HT121 was selected by screening of acid and bile salt tolerance and cholesterol assimilation assay. Sprague Dawley rats were randomly divided into three groups and fed the respective diets for 7 wk: normal chow diet (NCD), high-cholesterol diet (HCD), and high-cholesterol diet plus L. plantarum HT121 (HT121). After 7 wk, blood lipid profile was measured by enzyme-linked immunosorbent assay, gut microbiota was determined by 16 S rRNA sequencing, gene expression, and bile acids in liver were detected by transcriptome and metabolomics, respectively. L. plantarum HT121 feeding decreased serum triacylglycerols (TGs), total cholesterol (TC), and low-density lipoprotein (LDL), and increased serum high-density lipoprotein levels. HT121 treatment increased the α-diversity in the HT121 group to a level close to that in the NCD group, and restored the genera of Adlercreutzia, Mucispirillum, Ruminococcus, Clostridium, Blautia, Roseburia, and Akkermansia to levels similar to those in the NCD group. Furthermore, the high-cholesterol diet decreased taurocholic acid (TCA) and increased taurochenodeoxycholic acid (TCDCA) and glycocholic acid (GCA) in the liver; all these changes were reversed by HT121 treatment, bringing the levels close to those in the NCD group. Finally, HT121 treatment increased expression of bile secretion-related genes Cyp7 a1 in rat liver, which was positively correlated with TG, Clostridium, and GCA. Spearman's correlation analysis showed that TGs, TC, and LDL were positively correlated with the relative abundance of genera of Blautia, Clostridium, and Roseburia, and levels of bile acid glycocholic acid, and inversely correlated with the relative abundance of Ruminococcus and Mucispirillum. L. plantarum HT121 can improve serum lipid profiles in a high-fat diet-induced rat model, which may be attributed to alteration in gut microbiota and bile acid metabolism.

Protective effect of adropin against high fat diet-induced obese diabetic wistar rats via nuclear factor erythroid 2-related factor 2 pathway

Introduction: Liver steatosis (fatty liver) is frequently found during the conditions such as diabetes and obesity. The current experimental study was executed the effect of adropin against high fat diet (HFD)-induced obese diabetic Wistar rats via nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Materials and Methods: Wistar rats were randomly divided into six groups and divided as follows: normal, HFD control, HFD + adropin (2.5, 5 and 10 mg/kg), and HFD + Glibenclamide (2.5 mg/kg), respectively. Lipid and carbohydrate metabolism, hepatic parameters, antioxidant, and proinflammatory cytokines were estimated at the end of the experimental study. Nrf2 transcription and nuclear level were also estimated. In vitro adropin diminished the accumulation of lipid droplets in dose-dependent manner and no effect was observed on the lipolysis. Type II diabetic rats fed with HFD exhibited a marked reduction in hepatic extraction faction and hepatic steatosis after the adropin and glibenclamide treatment. Results: Adropin significantly (P

Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9 in hyperlipidemic rats

Hyperlipidemia (HPL) characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor (LDLR) in the lysosome of hepatocytes. Aloe-emodin (AE) is one of potentially bioactive components of Chinese traditional medicine Daming capsule. In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models. High-fat diet-induced rats were treated with AE (100 mg/kg per day, ig) for 6 weeks. We found that AE administration significantly decreased the levels of total cholesterol (TC) and LDL in the serum and liver tissues. Moreover, AE administration ameliorated HPL-induced hepatic lipid aggregation. But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats. A cellular model of HPL was established in human hepatoma (HepG2) cells treated with cholesterol (20 μg/mL) and 25-hydroxycholesterol (2 μg/mL), which exhibited markedly elevated cholesterol levels. The increased cholesterol levels could be reversed by subsequent treatment with AE (30 μM). In both the in vivo and in vitro HPL models, we revealed that AE selectively suppressed the sterol-regulatory element-binding protein-2 (SREBP-2) and hepatocyte nuclear factor (HNF)1α-mediated PCSK9 signaling, which in turn upregulated LDL receptor (LDLR) and promoted LDL uptake. This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway.

Acupuncture Targeting SIRT1 in the Hypothalamic Arcuate Nucleus Can Improve Obesity in High-Fat-Diet-Induced Rats with Insulin Resistance via an Anorectic Effect

Objective: To investigate the anorexigenic and anti-obesity effectiveness of electroacupuncture (EA) on high-fat-diet-induced (HFDI) obese rats with insulin resistance (IR) and to reveal the possible mechanisms of EA affecting SIRT1 (silent mating type information regulation 2 homolog 1) in the central nervous system (CNS). Methods: We divided 60 rats into 6 groups. All interventions, including EA and intracerebroventricular administration, were performed after 8 weeks of model establishment. We tested obesity phenotypes like body weight (BW) gain; food intake; and IR levels including glucose infusion rate, intraperitoneal insulin tolerance test (IPITT), and intraperitoneal glucose tolerance test (IPGTT) during treatment. We detected protein expression and microscopic locations in hypothalamic SIRT1, the transcription factor FOXO1 (forkhead box protein O1), acetylated FOXO1 (Ac-FOXO1), pro-opiomelanocortin (POMC), and neuropeptide Y (NPY) via Western blotting and immunofluorescence, and monitored gene expression by real-time polymerase chain reaction. Results: Like the SIRT1 agonist, EA suppressed BW gain and IR levels in obese rats, but this was only partially blocked by the SIRT1 antagonist. EA could upregulate protein expression of hypothalamic SIRT1 and downregulate the acetylation level of FOXO1 in the hypothalamic arcuate nucleus (ARC), which decreased gene expression of NPY and increased that of POMC. The agonist targeted the hypothalamic SIRT1 gene, unlike EA, which targeted posttranscriptional regulation. Conclusion: EA could improve obesity in HFDI rats with IR via its anorectic effect. This effect targeted posttranscriptional regulation of the SIRT1 gene, which induced upregulation of ARC FOXO1 deacetylation and mediated the gene expression of POMC and NPY.

EXPLORATION OF IN VIVO ANTIOXIDANT ACTIVITY OF 50% ETHANOLIC EXTRACT OF SESAMUM INDICUM L. SEED AGAINST HIGH FAT DIET INDUCED RATS

Objective: The aim of the present study was to investigate the in vivo antioxidant potential of 50% ethanolic extract of Sesamum indicum against high-fat diet-induced rats.&#x0D; Methods: Animals were treated with plant extract for 30 d, and a high-fat diet was given to all groups except plain control, throughout, out the study. And alpha-tocopherol acetate (Vit, E) was used as standard. Pre-treatment with 16 mg/100 gm of body weight of 50% ethanolic extract of Sesamum indicum improved the Superoxide dismutase, catalase, glutathione, and lipid peroxidation levels significantly as compared to control group.&#x0D; Results: The present studies revealed that Sesamum indicum has significant in vivo antioxidant activity and can be used to protect tissue from oxidative stress. The result showed that the activities of SOD, catalase, lipid peroxidase, and glutathione, in the group treated with high-fat diet declined significantly than that of normal group.&#x0D; Conclusion: 50% ethanolic extract of in the dose of Sesamum indicum 16 mg/100 gm of body weight, has improved the SOD, catalase, glutathione, and lipid peroxidase levels significantly, which were comparable with high-fat-diet-induced rats. Based on this study we conclude that the 50% ethanolic extract of Sesamum indicum possesses in vivo antioxidant activity and can be employed in protecting tissue from oxidative stress.

The potential of antioxidant-rich Maoberry (Antidesma bunius) extract on fat metabolism in liver tissues of rats fed a high-fat diet

BackgoundObesity and dyslipidemia are major risk factors associated with non-alcoholic fatty liver disease (NAFLD). NAFLD refers to the accumulation of fat in more than 5% of the liver without alcohol consumption. NAFLD is the most common liver disease and is rapidly becoming a global public health problem. Maoberry (Antidesma bunius) is a fruit rich in antioxidants, especially phenolic compounds, which are reported to have benefits for patients with NAFLD.MethodsWe evaluated the effect of Maoberry extract on fat metabolism in liver tissues of high fat diet–induced rats. Five (5) groups (n = 12) of male Sprague-Dawley (SD) rats were divided into those given a high fat diet with no treatment (HF), different dosages of Maoberry extracts (0.38 [ML], 0.76 [MM) and 1.52 [MH] g/kg body weight) and 10 mg/kg statin (STAT). The rats were fed a high fat diet for 4 weeks to induce obesity and subsequently continued more for 12 weeks with treatments of Maoberry extracts or STAT. The levels of triglyceride, liver enzymes, oxidative stress and inflammation markers, triglyceride synthesis regulators, and pathology of the liver in high fat diet-induced rats were investigated.ResultsFeeding Maoberry extract in MH groups resulted in decreasing levels of serum alanine aminotransferase (ALT), liver triglyceride, liver thiobarbituric acid reactive substances (TBARS) and mRNA expression of tumour necrosis factor (TNF)-α, interleukin (IL)-6, glycerol-3-phosphate acyltransferase (GPAT)-1 and acetyl-coenzyme A carboxylase (ACC) compared with the HF group (P < 0.05). Moreover, histopathological study of the liver showed reduced fat droplets in the Maoberry extract treatment groups, especially in MH groups and STAT treatment groups.ConclusionsThe improvements of fat metabolism in liver tissues of rats fed a high-fat diet were observed in Maoberry extracts treatment groups. The underline mechanism that link to fat metabolism might be through the process accompanied with down-regulated the gene expression of key enzymes of lipid production, antioxidant activity, and anti-inflammation properties of Maoberry extracts which contains high levels of phenolic and flavonoid compounds.

Passiflora edulis seed oil from west Cameroon: Chemical characterization and assessment of its hypolipidemic effect in high-fat diet-induced rats.

In this study, the in vivo hypolipidemic effect of west Cameroonian Passiflora edulis variety seed oil (PE) was assessed in female and male Wistar rats. The chemical properties of the oil were evaluated through the determination of the peroxide, iodine, and thiobarbituric acid values, as well as its fatty acid composition using gas chromatography. Results showed that the oil extraction yield was 19.90% and its quality indexes were as follows: peroxide value = 2.10 ± 0.20 meq O2/kg; thiobarbituric acid value = 0.25 ± 0.00 ppm; and iodine value = 97.40 ± 0.45 g I2/100 g. Its fatty acid composition showed that it contains about 84.88% of unsaturated fatty acid, linoleic acid being the most represented (68.39%), followed by oleic acid (14.31%). The administration of this oil resulted in a significant reduction (p < .05) in the level of triglycerides, total cholesterol, and low‐density lipoprotein‐cholesterol in rats. The PE groups showed a significant increase (p < .05) in high‐density lipoprotein‐cholesterol compared with untreated male rats. A similar trend was observed with female rats for triglycerides, but lowest values were observed with olive oil at 1 ml. This study suggests that P. edulis seed oil is rich in linoleic acid, which might be responsible for its hypolipidemic effect comparable to that of olive oil.

Effect of arabinoxylan on colonic bacterial metabolites and mucosal barrier in high-fat diet-induced rats.

The aim of this study was to demonstrate the effect of arabinoxylan on colonic mucosal barrier and metabolomic profiles in high‐fat diet‐induced rats. A total of 20 six‐week‐old male rats were arranged randomly to two groups (n = 10/group), including a high‐fat diet (HFD) group and a high‐fat supplemented with arabinoxylan diet (AXD) group. Results showed that feeding AXD reduced serum lipopolysaccharide in rats after 5 weeks. In colonic digesta, Escherichia coli population was reduced, while Lactobacillus, Bifidobacterium, and Bacteroidetes populations were increased in AXD group. Metabolomics assay found that the different abundances of 84 metabolites were observed, involving lipid, carbohydrate, and nitrogenous metabolism in colonic digesta. In colonic mucosa, AXD up‐regulated gene level of tight‐junction‐related proteins. Meanwhile, lower TNF‐α and IL‐1β levels were related to TLR4/NF‐κB/MyD88 pathway in AXD group. In conclusion, arabinoxylan could change colonic microbial metabolism and improve the colonic mucosal barrier via modulating intestinal microflora and tight junction proteins.

Green tea polyphenols attenuate hepatic steatosis, and reduce insulin resistance and inflammation in high-fat diet-induced rats.

Non‑alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and inflammation; however, the exact pathogenesis of NAFLD is not fully understood. Green tea polyphenols (GTP) exhibit beneficial effects against metabolic syndrome. However, the effect of GTP on NAFLD remains largely unknown. The aim of the present study was to investigate the effects of GTP on NAFLD in high‑fat diet (HFD)‑induced rats. The NAFLD rat model was induced with a HFD for 8weeks. A total of 30adult male Sprague Dawley rats were randomly divided into three groups: i) Normal control group; ii) HFD group; and iii) HFD with GTP group. Hematoxylin and eosin and OilRedO analyses were performed. The levels of alanine aminotransferase (ALT), aspartate amino-transferase (AST) and inflammatory cytokines in the serum, as well as oxidative stress markers and hepatic lipids in the liver were measured. In addition, parameters associated with glucose metabolism were also assessed. Western blotting and RT‑qPCR were used to determine the expression levels of 5'adenosine monophosphate‑activated protein kinase(AMPK). HFD‑induced rats exhibited features associated with NAFLD. GTP intervention significantly reduced serum ALT and AST levels. Fasting serum glucose, insulin resistance and hepatic lipid levels were all decreased in the GTP‑treated rats. GTP also significantly decreased the levels of TNF‑α, IL‑6 and malondialdehyde. In contrast, superoxide dismutase levels were increased in the liver. Furthermore, GTP also significantly increased phosphorylation of AMPK and attenuated histopathological changes indicative of injury in liver tissue. GTP has a protective effect on HFD‑induced hepatic steatosis, insulin resistance and inflammation, and the underlying mechanism may involve the AMPK pathway.

Barley grass juice (Hordeum vulgare L.) inhibits obesity and improves lipid profile in high fat diet-induced rat model

Ethnopharmacological relevanceHordeum vulgare (L.), commonly known as barley belonging to Poaceae family is a widely used cereal. Barley seeds are considered to possess high nutritional value and antioxidant properties. The grass of barley is also considered as a part of health drink in many parts of India. It is claimed to suppress a number of health disorders including obesity, diabetes, circulatory disorders, arthritis, anemia, excessive cholesterol levels, renal difficulties, and cancer. However, the antiobesity potential of barley grass has not been explored till now. Aim of the studyThe aim of the present study was to characterize and evaluate the anti-obesity activity of barley grass juice (Hordeum vulgare L.) in high fat diet induced model. Materials and methodsBarley grass juice was characterized by GC-MS analysis for identifying the active phytochemical constituents and was subjected to standard in vitro antioxidant studies. For in vivo studies, obesity was induced by high fat diet model in adult male Wistar rats. Atorvastatin (10 mg/kg) was used as the standard and barley grass juice was administered at two dose levels (200 and 400 mg/kg) for a period of 60 days. Anthropometric parameters, lipid profile and liver function markers were screened at regular intervals in all the treatment groups. At the end of the study, histopathological evaluations of liver and carotid artery were performed. The levels of in vivo antioxidant enzymes like SOD, catalase, reduced glutathione and lipid peroxidation in terms of malondialdehyde were also estimated in the liver homogenates. Expression levels of PPAR-gamma and caspase 3 were determined in the liver. ResultsResults indicated that barley grass juice (Hordeum vulgare L.) exhibited potent in vitro antioxidant activity. Rats administered with high fat diet for 60 days showed a significant increase in body weight, BMI, altered lipid profile, liver function markers like AST, ALT, ALP and increased expression of PPAR-gamma and caspase 3. However, administration of barley grass juice for 60 days, profoundly decreased the bodyweight, BMI, improved lipid profile and liver function markers. This was supported by the decreased expression of PPAR-gamma and caspase 3 in liver. Histopathological variations observed in liver and carotid artery of high fat diet group, when treated with BJG showed preserved hepatocytes and reduced atherosclerosis. GC-MS analysis identified the presence of 12 phytochemical constituents in barley grass juice. ConclusionOur study demonstrates the antiobesity activity of barley grass juice and it may be concluded that barley grass juice can be an effective nutraceutical in the management of obesity.

Prevention of Obesity and Hyperlipidemia by Heptamethoxyflavone in High-fat Diet-induced Rats.

Polymethoxyflavones (PMFs) have been shown to prevent obesity, ameliorate type 2 diabetes, and regulate lipid metabolism in vitro and in vivo. However, little is known about the contribution of 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) to prevent obesity and regulate lipid metabolism in vivo. We aimed to investigate the potential efficacy of HMF on preventing obesity and hyperlipidemia in rats fed a high-fat diet (HFD) and its underlying mechanisms. Male Sprague-Dawley rats were fed a normal diet or an HFD with or without HMF (0.02%, 0.04% and 0.08%, w/w) for 6 weeks. The supplementation of HMF not only significantly decreased body weight gain (HFD, 336.50 ± 18.84 g; LHMF, 309.43 ± 20.74 g; MHMF, 296.83 ± 13.88 g; HHMF, 265.71 ± 19.09 g; respectively, p < 0.05) and adipose tissues weight ( p < 0.05), but also markedly lowered serum levels of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol ( p < 0.05) in the sixth week in a dose-dependent manner compared with the HFD group. HMF also significantly alleviated hepatic steatosis in the liver (liver weight g/100 g body weight of HFD, 4.86 ± 0.11%; LHMF, 4.02 ± 0.33%; MHMF, 4.05 ± 0.31%; HHMF, 3.72 ± 0.34%; respectively, p < 0.05). Furthermore, transcriptome analysis and real-time quantitative RT-PCR demonstrated that HMF supplementation markedly downregulated hepatic genes related to adipogenesis transcription and inflammatory responses, and significantly upregulated genes related to fatty acid oxidation and energy expenditure. These results indicated that HMF could effectively prevent obesity and hyperlipidemia by regulation of the expression of lipid metabolism-related and inflammatory response-related genes.

Dysregulation of cardiac lipid parameters in high-fat high-cholesterol diet-induced rat model

BackgroundLipid dysregulation is a classical risk factor for cardiovascular disease (CVD), yet scanty evidence existed regarding cardiac lipid metabolism that is directly related to heart damage. Recently, the relationship between dyslipidemia and pro-inflammatory insults has led to further understanding on the CVD-predisposing effects of dyslipidemia. The aims of the present study were to investigate whether high-fat high-cholesterol (HFHC) diet-induced hyperlipidemia would cause heart damage and to study the potential role of local cardiac lipid dysregulation in the occurrence of cellular injury.MethodsMale Sprague–Dawley rats were divided into normal chow or HFHC diet groups, and sacrificed after 2 or 4 weeks, respectively. Lipid peroxidation marker level was measured. Lipid parameters in the rat hearts were detected. Cardiac damage was evaluated.ResultsHFHC diet increased serum levels of cholesterol and free fatty acids (FFAs) and led to systemic oxidative stress and pro-inflammatory status. Cardiac lipid dysregulation, which was characterized by elevated levels of cholesterol and adipocyte (A)- and heart (H)-fatty acid binding proteins (FABPs), occurred after HFHC diet for 4 weeks. Cardiac damage was further evident with elevated circulating H-FABP levels, increased cardiac interstitial fibrosis and the loss of troponin I.ConclusionOur data demonstrated that HFHC diet led to systemic and cardiac lipid dysregulation, accompanied by systemic oxidative and pro-inflammatory stresses, and these may finally cooperate to cause a series of pathological changes of the heart tissue. Our findings suggest that maintenance of lipid regulation may be essential in the prevention of heart damage.

Attenuation of High-Fat Diet-Induced Rat Liver Oxidative Stress and Steatosis by Combined Hydroxytyrosol- (HT-) Eicosapentaenoic Acid Supplementation Mainly Relies on HT.

Pharmacological therapy for nonalcoholic fatty liver disease (NAFLD) is not approved at the present time. For this purpose, the effect of combined eicosapentaenoic acid (EPA; 50 mg/kg/day) modulating hepatic lipid metabolism and hydroxytyrosol (HT; 5 mg/kg/day) exerting antioxidant actions was evaluated on hepatic steatosis and oxidative stress induced by a high-fat diet (HFD; 60% fat, 20% protein, and 20% carbohydrates) compared to a control diet (CD; 10% fat, 20% protein, and 70% carbohydrates) in mice fed for 12 weeks. HFD-induced liver steatosis (i) was reduced by 32% by EPA, without changes in oxidative stress-related parameters and mild recovery of Nrf2 functioning affording antioxidation and (ii) was decreased by 42% by HT, concomitantly with total regain of the glutathione status diminished by HFD, 42% to 59% recovery of lipid peroxidation and protein oxidation enhanced by HFD, and regain of Nrf2 functioning, whereas (iii) combined EPA + HT supplementation elicited 74% reduction in liver steatosis, with total recovery of the antioxidant potential in a similar manner than HT. It is concluded that combined HT + EPA drastically decreases NAFLD development, an effect that shows additivity in HT and EPA effects that mainly relies on HT, strengthening the impact of oxidative stress as a central mechanism underlying liver steatosis in obesity.