High-fructose Diet Rats Research Articles

Antioxidant Effects of Gude Bean (Cajanus cajan) to Homa-IR and IRS-1 of High Fat and High Fructose Diet Rats

This study aimed to determine the effect of antioxidants in Gude bean (Cajanus cajan) treatment on HOMA-IR level and IRS-1 gene expression on the rats induced with high fat and high fructose diet. This study used 25 male white rats (Rattus norvegicus) in two control groups and three treatment groups. The measurement of HOMA-IR was done before and after treatment using the blood plasma while IRS-1 measurement was after treatment using the muscle tissue. The results showed that rat blood glucose level after being induced high fat and high fructose diet reached average value higher (p<0.05) compared to the Normal group. The Gude bean treatment resulted the decrease of HOMA-IR level (p<0.05) and the increase of IRS-1 (p<0.05). Gude bean treatment can inhibit insulin signal interference by ROS synthesis inhabitation by decreasing HOMA-IR level and increase IRS-1 gene expression in rats induced high fat and fructose diet.

Effects of Melatonin Supplementation on the Aortic Wall in a Diet-Induced Obesity Rat Model.

Background Cardiovascular disease (CVD) is still the leading cause of death globally. Alterations in the arterial wall architecture predict CVD morbidity and mortality and are associated with other CVD risk factors. Aortic wall thickness is closely linked to short- and long-term CVD morbidity and mortality, even without pronounced atherosclerotic changes.Obesity increases the risk of a broad spectrum of pathologies with vascular manifestation,which are oftenpathogenically associated with chronic oxidative stress and inflammatory response. Hence, as an antioxidant and anti-inflammatory agent, the pineal gland hormone melatonin is expected to have vasoprotective effects. This study evaluated the effects of melatonin supplementation on aortic wall thickness by assessing the cross-sectional associations of abdominal obesity with aortic intima-media thickness in a diet-induced obesity rat model. Methodology The model comprised of male Wistar rats that were on a high-fructose diet (HFD) (20% glucose-fructose corn syrup) for 12 weeks; the rats were divided into four groups (n = 8): control, HFD, HFD and melatonin supplementation (per os- 4 mg/kg/24h), and control and melatonin supplementation. All rats received a standard rodent diet and tap water. Zoometric measurements and the Lee index were calculated. Morphometric analysis of the abdominal aorta was performed by staining with hematoxylin-eosin and measuring the thickness of the abdominal aortic wall. For this, we used the Aperio Image Scope software. To evaluate the functional properties of the abdominal aorta, the modified Kernogan's index (KI) was employed. Results The results showed significantly elevated body weight (Lee index), KI, and wall thickness of the aorta abdominalis with morphometric changes in the vessel wall in HFD rats compared to the control group. Melatonin supplementation prevented these changes. Conclusions The administration of HFD to Wistar rats led to pathomorphological and morphometric changes in their abdominal aorta, which constitute the main diagnostic criteria of endothelial dysfunction. Melatonin supplementation regressed vascular wall remodeling and restored its functional capacity.

HIGH FRUCTOSE DIET INCREASES RENAL CHREBP-BETA EXPRESSION AND LEADS TO INTRA-RENAL FAT ACCUMULATION IN A METABOLIC-LIKE SYNDROME RAT MODEL

Objective: A high fructose diet induces metabolic syndrome (MeS) which includes ectopic lipid accumulation, such as fatty liver. MeS is also associated with chronic kidney disease (CKD). A novel isoform of ChREBP, ChREBPb, was recently reported to regulate liver fructose metabolism that leads to fatty liver development. The aim of this study was to evaluate fructose metabolism in the kidney and whether this metabolism leads to intra-renal fat accumulation. Design and method: In-vivo: Sprague Dawley rats were fed either normal chow (Ctrl) or a high fructose diet (HFrD) for eight weeks. Blood pressure, fasting blood glucose and triglycerides were measured. The kidneys were harvested for ChREBPb and de novo lipogenesis (DNL) gene expression, triglyceride content and histopathology staining. In-vitro: HK2 (human kidney) cells were treated with fructose for 48 h and gene expression for ChREBPb and DNL were determined. Results: The HFrD rats exhibited higher blood pressure (152 vs. 138 mmHg), glucose (146 vs. 127 mg/dl) and triglyceride (280 vs. 143 mg/dl) levels. Kidneys weight normalized to body weight of the HFrD rats were significant higher than the Ctrl (7.32 vs. 5.87). The difference can be explained by the higher triglyceride content in the HFrD kidneys (16.4 vs. 12.4 mg). Oil red staining revealed higher lipid droplet formation in the HFrD kidneys, which was also supported by higher adipophilin mRNA expression. The expression level of ChREBPb and its downstream genes, scd and fasn, were elevated in the HFrD kidney. Treating HK2 cells with 40 mM fructose increased ChREBPb expression levels. Its downstream genes, fasn and acc, also showed an increasing trend. In three out of five experiments, adipophilin was increased as well. Conclusions: In this study, we demonstrated that fructose consumption leads to intra-renal lipid accumulation and to the formation of a fatty kidney. This suggests a potential mechanism that can partially explain CKD development in fructose induced MeS.

High-Fructose Diet Increases Renal ChREBPβ Expression, Leading to Intrarenal Fat Accumulation in a Rat Model with Metabolic Syndrome.

Simple SummaryFructose consumption leads to the development of metabolic syndrome. Fatty liver and chronic kidney disease are closely related to metabolic syndrome. Lately, a transcription factor that regulates fructose metabolism in the liver, named ChREBPβ, which is responsible for de-novo lipogenesis and intra-hepatic fat accumulation (“fatty liver”), was described. In this study, we demonstrate that the effect of fructose consumption on the kidneys resembles its liver effect. Rats fed with a high-fructose diet exhibit bigger kidneys with higher triglycerides content, compared to control rats. The expression of ChREBPβ and its downstream genes was upregulated as well. Treating kidney-origin cells with fructose increased the expression of this factor as well, showing the direct effect of fructose on this factor. Thus, the appearance of fatty kidney in response to high-fructose consumption revealed a new mechanism linking metabolic syndrome to chronic kidney disease.Fructose consumption is associated with metabolic syndrome (MeS). Dysregulated lipid metabolism and ectopic lipid accumulation, such as in “fatty liver’’, are pivotal components of the syndrome. MeS is also associated with chronic kidney disease (CKD). The aim of this study was to evaluate kidney fructose metabolism and whether the addition of fructose leads to intrarenal fat accumulation. Sprague Dawley rats were fed either normal chow (Ctrl) or a high-fructose diet (HFrD). MeS features such as blood pressure and metabolic parameters in blood were measured. The kidneys were harvested for ChREBPβ and de novo lipogenesis (DNL) gene expression, triglyceride content and histopathology staining. HK2 (human kidney) cells were treated with fructose for 48 h and gene expression for ChREBPβ and DNL were determined. The HFrD rats exhibited higher blood pressure, glucose and triglyceride levels. The kidney weight of the HFrD rats was significantly higher than Ctrl rats. The difference can be explained by the higher triglyceride content in the HFrD kidneys. Oil red staining revealed lipid droplet formation in the HFrD kidneys, which was also supported by increased adipophilin mRNA expression. For ChREBPβ and its downstream genes, scd and fasn, mRNA expression was elevated in the HFrD kidneys. Treating HK2 cells with 40 mM fructose increased the expression of ChREBPβ. This study demonstrates that fructose consumption leads to intrarenal lipid accumulation and to the formation of a “fatty kidney”. This suggests a potential mechanism that can at least partially explain CKD development in fructose-induced MeS.

Does fructose have a protective role on migraine?-experimental evidence in a rat model of metabolic syndrome under omega-3 supplementation.

BackgroundMigraine is a highly disabling disease, for which current therapies are limited to symptom alleviation. There is compelling evidence linking migraine with metabolic disorders, but the causal relationship is not clear. Omega-3 (n-3) fatty acids have anti-inflammatory properties, with clear benefits in metabolic disorders, but its effects on migraine remains to be tested. We hypothesized that fructose-induced metabolic syndrome could aggravate migraine by increasing neuroinflammation and that n-3 treatment could mitigate it.MethodsMale Wistar rats were used. Animals that received 10% high fructose diet (HFD) or tap water were subdivided into two additional groups: with or without n-3 supplementation. Fifteen days before euthanasia, each group was subdivided into two additional groups: with or without nitroglycerin (NTG)-induced migraine.ResultsHFD lessened the migraine-like painful symptoms, as indicated by decreased grimace scores, which paralleled with reduced CGRP and leptin serum levels, increased hypothalamic CGRP, and decreased hypothalamic adiponectin and IL-6. There was a recovery of body and adipose tissue weight, besides a reduction of crown-like structures (CLS) in the inguinal adipose tissue. N-3 supplementation had no effect on NTG-related pain, but it decreased body and adipose tissue weight of HFD and tap water NTG-injected rats. N-3 improved NTG-related affective behavior and inflammatory parameters in tap water NTG-injected rats, with decreased hypothalamic TNF, serum CGRP and inguinal adipose-tissue CLS.ConclusionsHFD relieved NTG-induced pain, possibly due to decreased energy expenditure, minimizing migraine energy needs. N-3 exhibited favorable effects regarding affective behavior and central and peripheral inflammation, irrespective of HFD.

Comparison of the effects of sulforaphane and pioglitazone on insulin resistance and associated dyslipidemia, hepatosteatosis, and endothelial dysfunction in fructose-fed rats

The purpose of this work was to compare the influences of sulforaphane (SFN) to those of the standard insulin sensitizer pioglitazone (PIO) on high fructose diet (HFrD)-induced insulin resistance, dyslipidemia, hepatosteatosis, and vascular dysfunction in rats.Male Sprague Dawley rats (150–200 g) were fed on a standard diet (control) or a high fructose diet (HFrD, 60% w/w fructose) for 60 days. From day 16, two subgroups of HFrD-fed rats received either SFN (0.5 mg/kg/day, orally) or PIO (5 mg/kg/day, orally) along with HFrD until the end of the experiment.Fructose-fed rats showed significant decreases in food intake, body weight and feeding efficiency; effects that were not altered by either treatment. Data from insulin tolerance test (ITT), oral glucose tolerance test (OGTT), and HOMA-IR and HOMA-β indices demonstrated impaired insulin sensitivity and glucose utilization in HFrD-fed rats.SFN and PIO treatments significantly reduced OGTTAUC (Glass's Delta values = 1.12 and 0.84, respectively), decreased ITTAUC (Glass's Delta values = 1.05 and 0.71, respectively), significantly diminished HOMA-IR index (by 55.6% and 77.6%, respectively), and increased HOMA-β value (by 1.8 and 1.3 fold, respectively) compared to the HFrD rats. Moreover, SFN and PIO ameliorated hepatic oxidative stress and reduced serum levels of C-reactive protein and lactate dehydrogenase in HFrD-fed rats. Furthermore, SFN and PIO administrations improved insulin resistance-associated heaptosteatosis and enhanced vascular responsiveness to acetylcholine-induced relaxations. However, only SFN was able to enhance serum HDL-C levels in HFrD group.These finding suggests that SFN elicited insulin-sensitizing, hepatoprotective, and vasculoprotective effects in HFrD insulin-resistant rats that were comparable to those exerted by PIO.

Inhibition of sEH prevents high fructose‐induced impairement of myocardial oxygen comsumption in young rats

High fructose diet increases tissue oxidative stress and has been shown to be detrimental to cardiac function. Epoxyeicosainoic acids (EETs) are metabolites of arachidonic acid, which possess cardioprotective properties and are metabolized by soluble epoxide hydrolase (sEH). Therefore, inhibition of sEH is proven to be beneficial to cardiovascular function. The specific impact of a high fructose diet and the role of EETs/sEH in the regulation of cardiac function in the adolescent population have not been studied. To test the hypothesis that sEH inhibition attenuates the adverse action of fructose consumption on the heart of young rats, 4 week old rats were fed a normal diet (as control; ND) or a high fructose diet (HFD) for 30 days, without or with concomitant administration of TPPU, a specific sEH inhibitor, by oral‐gavage (1mg/kg body weight: HFD‐TPPU).MethodsCardiac output was analyzed by echocardiography and blood pressure was recorded using tail‐cuff measurements. Myocardial oxygen consumption (MV̇o2) was measured in freshly isolated left ventricular tissue from all groups of rats under control conditions and following incubation of tissue with the nitric oxide (NO) synthase inhibitor Nω‐nitro‐l‐arginine methyl ester (L‐NAME; 10−4M), or NADPH oxidase inhibitor (Nox), apocynin (10−4M) for 1 hour. Cytosolic and mitochondrial superoxide levels were determined by HPLC‐fluorescence detection via incubation of myocardial tissues with dihydroethidium (DHE) or Mitosox. Nox 2 expression was measured via western blot analysis.ResultsFructose feeding significantly impaired MV̇o2 compared to hearts of ND rats, as indicated by the loss of NO‐mediated regulation of MV̇o2. Incubation of myocardial tissue isolated from the ND group with L‐NAME yielded the same pattern as fructose feeding, further confirming that the NO‐mediated response is compromised with high fructose consumption. The treatment of HFD rats with TPPU normalized their MV̇o2 to the level of ND rats. Furthermore, incubation of myocardial tissues isolated from HFD rats with apocynin elicited normalized MV̇o2, comparable to that observed in HFD‐TPPU rats. In addition, mitochondrial superoxide and Nox 2 expression were significantly increased in myocardial tissue of HFD rats compared to ND and HFD‐TPPU rats. Thus, we conclude that 1) high fructose‐induced increase in oxidative stress is responsible for impaired NO‐mediated regulation of MV̇o2. 2) Inhibition of sEH reversed the oxidative stress‐induced impairment of MV̇o2 via perhaps, increases in tissue levels of antioxidant EETs.Support or Funding InformationThis work was supported by HL070653 and HL129797This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Gallic Acid Alleviates Hypertriglyceridemia and Fat Accumulation via Modulating Glycolysis and Lipolysis Pathways in Perirenal Adipose Tissues of Rats Fed a High-Fructose Diet.

This study investigated the ameliorative effect of gallic acid (GA) on hypertriglyceridemia and fat accumulation in perirenal adipose tissues of high-fructose diet (HFD)-induced diabetic rats. The previous results showed that orally administered GA (30 mg/kg body weight) for four weeks significantly reduced the levels of plasma glucose and triglyceride (TG) in HFD rats. GA also markedly decreased the perirenal adipose tissues weight of HFD rats in present study (p < 0.05). Western blot assay indicated that GA restored expression of insulin signaling-related proteins, such as insulin receptor (IR), protein kinase C-zeta (PKC-ζ), and glucose transporter-4 (GLUT4) in the perirenal adipose tissues of HFD rats. Moreover, GA enhanced expression of glycolysis-related proteins, such as phosphofructokinase (PFK) and pyruvate kinase (PK), and increased the expression of lipolysis-related proteins, such as adipose triglyceride lipase (ATGL), which is involved in lipolysis in the perirenal adipose tissues of HFD rats. This study revealed that GA may alleviate hypertriglyceridemia and fat accumulation through enhancing glycolysis and lipolysis pathways in perirenal adipose tissues of HFD rats. These findings also suggest the potential of GA in preventing the progression of diabetes mellitus (DM) complications.

α-Amyrin attenuates high fructose diet-induced metabolic syndrome in rats.

This study investigated the effect of α-amyrin (a pentacyclic triterpene) on high-fructose diet (HFD)-induced metabolic syndrome in rats. Male Wistar rats were randomly distributed into different groups. The control group was fed normal rat chow diet. The HFD group was fed HFD (60%; w/w) for 42 days. Pioglitazone (10 mg/kg, orally, once daily) was used as a standard drug. α-Amyrin was administered in 3 doses (50, 100, and 200 mg/kg, orally, once daily along with HFD). Plasma glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were estimated. Changes in blood pressure, oral glucose tolerance, and insulin tolerance were measured. Hepatic oxidative stress as well as messenger RNA (mRNA) and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) were analyzed. A significant increase in systolic blood pressure, plasma glucose, total cholesterol, and plasma triglycerides and a significant decrease in HDL-C were observed in HFD rats as compared with control rats. Glucose tolerance and insulin tolerance were also significantly impaired with HFD. α-Amyrin prevented these changes in a dose-dependent manner. Hepatic oxidative stress as well as micro- and macrovesicular fatty changes in hepatocytes caused by HFD were also attenuated by α-amyrin. α-Amyrin preserved the hepatic mRNA and protein levels of PPAR-α, which was reduced in HFD group. This study thus demonstrates that α-amyrin attenuates HFD-induced metabolic syndrome in rats.

Goji fruit (Lycium barbarum) protects sciatic nerve function against crush injury in a model of diabetic stress

Excess fructose consumption causes changes in functioning of the central and peripheral nervous systems, which increase the vulnerability of peripheral nerves to traumatic injury. The aim of this study was to evaluate the electrophysiological parameters of responses of motoneurons of the spinal cord at high-frequency stimulation of the distal part of the injured sciatic nerve in a model of diabetic stress under action of Lycium barbarum (LB). Male albino rats were given with drinking water with 50% concentration of dietary fructose for 6 weeks. Starting on the 7th week a crush injury of the left sciatic nerve was carried out. Some of the animals received fructose post-injury for 3 weeks and some of the animals received fructose+dry LB fruits for 3 weeks. In the fructose+crush+LВ group a relatively proportional division of tetanic and posttetanic potentiation and depression in responses of ipsilateral and contralateral motoneurons was observed, which would suggest the modulatory role of LB in short-term synaptic plasticity formation. Generally, LB fruit is able to modulate central nervous system reorganization, amplifying positive adaptive changes that improve functional recovery and promote selective target reinnervation in high fructose-diet rats with sciatic nerve crush-injury.

Fermented Red Ginseng Potentiates Improvement of Metabolic Dysfunction in Metabolic Syndrome Rat Models.

Metabolic syndrome including obesity, dyslipidemia and hypertension is a cluster of risk factors of cardiovascular disease. Fermentation of medicinal herbs improves their pharmacological efficacy. Red ginseng (RG), a widely used traditional herbal medicine, was reported with anti-inflammatory and anti-oxidant activity. Aim in the present study was to investigate that the effects of fermented red ginseng (FRG) on a high-fructose (HF) diet induced metabolic disorders, and those effects were compared to RG and losartan. Animals were divided into four groups: a control group fed a regular diet and tap water, and fructose groups that were fed a 60% high-fructose (HF) diet with/without RG 250 mg/kg/day or FRG 250 mg/kg/day for eight weeks, respectively. Treatment with FRG significantly suppressed the increments of body weight, liver weight, epididymal fat weight and adipocyte size. Moreover, FRG significantly prevented the development of metabolic disturbances such as hyperlipidemia and hypertension. Staining with Oil-red-o demonstrated a marked increase of hepatic accumulation of triglycerides, and this increase was prevented by FRG. FRG ameliorated endothelial dysfunction by downregulation of endothelin-1 (ET-1) and adhesion molecules in the aorta. In addition, FRG induced markedly upregulation of Insulin receptor substrate 1 (IRS-1) and glucose transporter type 4 (Glut4) in the muscle. These results indicate that FRG ameliorates obesity, dyslipidemia, hypertension and fatty liver in HF diet rats. More favorable pharmacological effects on HF diet induced metabolic disorders were observed with FRG, compared to an equal dose of RG. These results showed that the pharmacological activity of RG was enhanced by fermentation. Taken together, fermentated red ginseng might be a beneficial therapeutic approach for metabolic syndrome.

Vescalagin from Pink Wax Apple [Syzygium samarangense (Blume) Merrill and Perry] Alleviates Hepatic Insulin Resistance and Ameliorates Glycemic Metabolism Abnormality in Rats Fed a High-Fructose Diet.

This study investigates the ameliorative effect of vescalagin (VES) isolated from Pink wax apple fruit on hepatic insulin resistance and abnormal carbohydrate metabolism in high-fructose diet (HFD)-induced hyperglycemic rats. The results show that in HFD rats, VES significantly reduced the values of the area under the curve for glucose in an oral glucose tolerance test and the homeostasis model assessment of insulin resistance index. VES significantly enhanced the activity of hepatic antioxidant enzymes while reducing thiobarbituric acid-reactive substances in HFD rats. Western blot assay revealed that VES reduced hepatic protein expression involved in inflammation pathways while up-regulating expression of hepatic insulin signaling-related proteins. Moreover, VES up-regulated the expression of hepatic glycogen synthase and hepatic glycolysis-related proteins while down-regulating hepatic gluconeogenesis-related proteins in HFD rats. This study suggests some therapeutic potential of VES in preventing the progression of diabetes mellitus.

Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet

Herein, we investigated the hypoglycemic effect of plant gallic acid (GA) on glucose uptake in an insulin-resistant cell culture model and on hepatic carbohydrate metabolism in rats with a high-fructose diet (HFD)–induced diabetes. Our hypothesis is that GA ameliorates hyperglycemia via alleviating hepatic insulin resistance by suppressing hepatic inflammation and improves abnormal hepatic carbohydrate metabolism by suppressing hepatic gluconeogenesis and enhancing the hepatic glycogenesis and glycolysis pathways in HFD-induced diabetic rats. Gallic acid increased glucose uptake activity by 19.2% at a concentration of 6.25μg/mL in insulin-resistant FL83B mouse hepatocytes. In HFD-induced diabetic rats, GA significantly alleviated hyperglycemia, reduced the values of the area under the curve for glucose in an oral glucose tolerance test, and reduced the scores of the homeostasis model assessment of insulin resistance index. The levels of serum C-peptide and fructosamine and cardiovascular risk index scores were also significantly decreased in HFD rats treated with GA. Moreover, GA up-regulated the expression of hepatic insulin signal transduction–related proteins, including insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3 kinase, Akt/protein kinase B, and glucose transporter 2, in HFD rats. Gallic acid also down-regulated the expression of hepatic gluconeogenesis–related proteins, such as fructose-1,6-bisphosphatase, and up-regulated expression of hepatic glycogen synthase and glycolysis-related proteins, including hexokinase, phosphofructokinase, and aldolase, in HFD rats. Our findings indicate that GA has potential as a health food ingredient to prevent diabetes mellitus.

NFAT inhibitor tributylhexadecylphosphoniumbromide, ameliorates high fructose induced insulin resistance and nephropathy

High fructose diet (HFrD)-induced insulin resistance (IR) has been reported to be associated with an increase in albuminuria, glomerular hypertrophy and inflammation in kidney. However, the molecular mechanisms associated with high fructose-induced IR and renal dysfunction are still unclear. In the present study, we have investigated the role of nuclear factor of activated T-cell (NFAT) and its inhibitor, Tributylhexadecylphosphoniumbromide (THPB) in high fructose-induced IR and renal injury. NFAT inhibition by THPB treatment significantly improved HFrD-induced insulin resistance. Treatment with THPB markedly reduced high fructose diet-induced protein expression of NFATc4, PTEN and also alleviated expression of inflammatory markers in kidneys of HFrD rats. Further, THPB treatment not only improved acute ANG II responses but also repressed the processes of renal fibrosis, ECM accumulation, foot process effacement and renal apoptosis in HFrD rats. Taken together, we for the first time provide evidence that HFrD -induced insulin resistance and renal injury is associated with dysregulated NFATc4/PTEN signalling and THPB prevents this dysregulation through inhibition of NFATc4. Thus, targeting NFATc4 can be a novel therapeutic approach for preventing HFrD induced- IR and renal injury.

Effects of Fermented Red Ginseng on High‐Fructose induced Metabolic Syndrome

The red ginseng (RG), a widely used traditional herbal medicine, was reported with anti‐inflammatory and anti‐oxidant activity. Aim in the present study was to investigate that the effects of fermented red ginseng (FRG) on high‐fructose (HF) diet induced metabolic disorders, and those effects were compared to RG and losartan. Treatment with FRG was significantly suppressed the increments of body weight, liver weight, epididymal fat weight and adipocyte size. Moreover, FRG significantly prevented the development of the metabolic disturbances such as hyperlipidemia and hypertension. Staining with Oil‐red‐o demonstrated marked increase of hepatic accumulation of triglycerides, and this increases was prevented by FRG. FRG ameliorated endothelial dysfunction by down‐regulation of endothelin‐1 (ET‐1) and adhesion molecules in the aorta. In addition, FRG induced markedly up‐regulation of IRS‐1 and Glut4 in the muscle. These results indicate that FRG ameliorates obesity, dyslipidemia, hypertension and fatty liver in HF diet rats. Thus the pharmacological activity of RG was enhanced by fermentation on HF diet induced metabolic disorders. Taken together, fermentated red geinseng might be a beneficial therapeutic approach for metabolic syndrome.

Protective effect of thymoquinone against high-fructose diet-induced metabolic syndrome in rats.

Thymoquinone (TQ), a bioactive constituent of Nigella sativa (Linn.) seed, which is commonly used as a spice in Asian food, has been reported to possess a wide range of biological effects. The present study evaluated the effect of TQ on high-fructose diet (HFD)-induced metabolic syndrome (MetS) in male Wistar rats. MetS was induced by 60% HFD over 42 days. TQ (25, 50 and 100 mg/kg, p.o. once daily) was administered along with HFD for 42 days. Pioglitazone (10 mg/kg, p.o. once daily) was used as a standard drug. Plasma glucose, triglycerides, total cholesterol and HDL-cholesterol were estimated on days 0 and 42. Change in blood pressure, oral glucose tolerance and insulin resistance were measured. Hepatic thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase levels were estimated as measures of hepatic oxidative stress. Hepatic mRNA of PPAR-α and PPAR-γ was also studied. TQ prevented the characteristic features of HFD-induced MetS, such as hyperglycaemia, hypertriglyceridemia, hypercholesterolaemia and elevated systolic blood pressure. TQ also prevented impaired glucose tolerance and insulin resistance. It also ameliorated HFD-induced increase in hepatic TBARS and depletion of SOD, catalase and GSH. TQ prevented reduction in hepatic mRNA of PPAR-α and PPAR-γ in HFD rats, and the effects were comparable to those of pioglitazone. This study demonstrates protective effect of TQ against HFD-induced MetS on rats which might have been mediated via PPAR mechanism.

Protective effect of umbelliferone on high-fructose diet-induced insulin resistance and oxidative stress in rats

The present study was designed to investigate the effect of umbelliferone (UMB) on insulin resistance (IR) and oxidative stress in rats fed a high fructose diet (HFD). Male Wistar rats received a daily diet containing either 60% fructose or 60% starch. They were administered with the UMB at three different doses (10, 20 and 40mg/kg, p.o) from the 16th day. At the end of 60 days, HFD rats exhibited significant increases in plasma glucose and insulin levels. The activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and the levels of non-enzymic antioxidants such as vitamin C, vitamin E and reduced glutathione were decreased while increases in the levels of lipid peroxidative markers were observed in liver tissues of HFD rats as compared to control rats. In addition, rats fed a HFD with UMB reversed all the above changes to near normal in a dose dependent manner. The effect at a dose of 40mg/kg b.w/day was more pronounced than the other two doses (10 and 20mg/kg b.w/day). Biochemical findings were supported by histological studies. These results indicated that administration of UMB may be a feasible therapeutic strategy for prevention of a high-fructose diet-induced insulin resistance and oxidative stress.

Gastrodia elata Ameliorates High‐Fructose Diet‐Induced Lipid Metabolism and Endothelial Dysfunction

Overconsumption of fructose results in dyslipidemia, hypertension, and impaired glucose tolerance, which have documented correlation with metabolic syndrome. Gastrodia elata, a widely used traditional herbal medicine, was reported with anti-inflammatory and antidiabetes activities. Thus, this study examined whether ethanol extract of Gastrodia elata Blume (EGB) attenuate lipid metabolism and endothelial dysfunction in a high-fructose (HF) diet animal model. Rats were fed the 65% HF diet with/without EGB 100 mg/kg/day for 8 weeks. Treatment with EGB significantly suppressed the increments of epididymal fat weight, blood pressure, plasma triglyceride, total cholesterol levels, and oral glucose tolerance, respectively. In addition, EGB markedly prevented increase of adipocyte size and hepatic accumulation of triglycerides. EGB ameliorated endothelial dysfunction by downregulation of endothelin-1 (ET-1) and adhesion molecules in the aorta. Moreover, EGB significantly recovered the impairment of vasorelaxation to acetylcholine and levels of endothelial nitric oxide synthase (eNOS) expression and induced markedly upregulation of phosphorylation AMP-activated protein kinase (AMPK)α in the liver, muscle, and fat. These results indicate that EGB ameliorates dyslipidemia, hypertension, and insulin resistance as well as impaired vascular endothelial function in HF diet rats. Taken together, EGB may be a beneficial therapeutic approach for metabolic syndrome.

Cardiovascular depression in rats exposed to inhaled particulate matter and ozone: effects of diet-induced metabolic syndrome.

Background: High ambient levels of ozone (O3) and fine particulate matter (PM2.5) are associated with cardiovascular morbidity and mortality, especially in people with preexisting cardiopulmonary diseases. Enhanced susceptibility to the toxicity of air pollutants may include individuals with metabolic syndrome (MetS).Objective: We tested the hypothesis that cardiovascular responses to O3 and PM2.5 will be enhanced in rats with diet-induced MetS.Methods: Male Sprague-Dawley rats were fed a high-fructose diet (HFrD) to induce MetS and then exposed to O3, concentrated ambient PM2.5, or the combination of O3 plus PM2.5 for 9 days. Data related to heart rate (HR), HR variability (HRV), and blood pressure (BP) were collected.Results: Consistent with MetS, HFrD rats were hypertensive and insulin resistant, and had elevated fasting levels of blood glucose and triglycerides. Decreases in HR and BP, which were found in all exposure groups, were greater and more persistent in HFrD rats compared with those fed a normal diet (ND). Coexposure to O3 plus PM2.5 induced acute drops in HR and BP in all rats, but only ND rats adapted after 2 days. HFrD rats had little exposure-related changes in HRV, whereas ND rats had increased HRV during O3 exposure, modest decreases with PM2.5, and dramatic decreases during O3 plus PM2.5 coexposures.Conclusions: Cardiovascular depression in O3- and PM2.5-exposed rats was enhanced and prolonged in rats with HFrD-induced MetS. These results in rodents suggest that people with MetS may be prone to similar exaggerated BP and HR responses to inhaled air pollutants.Citation: Wagner JG, Allen K, Yang HY, Nan B, Morishita M, Mukherjee B, Dvonch JT, Spino C, Fink GD, Rajagopalan S, Sun Q, Brook RD, Harkema JR. 2014. Cardiovascular depression in rats exposed to inhaled particulate matter and ozone: effects of diet-induced metabolic syndrome. Environ Health Perspect 122:27–33; http://dx.doi.org/10.1289/ehp.1307085

Hypotriglyceridemic and hypoglycemic effects of vescalagin from Pink wax apple [Syzygium samarangense (Blume) Merrill and Perry cv. Pink] in high-fructose diet-induced diabetic rats

Vescalagin, an active component from Pink wax apple [Syzygium samarangense (Blume) Merrill and Perry cv. Pink] fruit, with glucose uptake enhancing ability in insulin-resistant FL83B mouse hepatocytes, as shown in our previous study, was further evaluated for its hypotriglyceridemic and hypoglycemic effects in high-fructose diet (HFD)-induced diabetic rats. Wistar rats were fed HFD for 16weeks and orally administered with vescalagin from Pink wax apple daily during the last 4weeks. The results of biochemical parameters showed that fasting blood glucose, C-peptide, fructosamine, triglyceride and free fatty acid contents decreased by 44.7%, 46.2%, 4.0%, 42.5%, and 10.8%, respectively, in the HFD-induced diabetic rats administered with vescalagin at 30mg/kg body weight in comparison with those of control HFD-induced diabetic rats. However, high-density-lipoprotein-cholesterol content increased by 14.4% in the HFD rats treated with vescalagin. The present study reveals that vescalagin could have therapeutic value against diabetic progression via its anti-hypertriglyceridemic and anti-hyperglycemic effects.