scholarly journals Amelioration of High Fructose Diet-Induced Insulin Resistance, Hyperuricemia, and Liver Oxidative Stress by Combined Use of Selective Agonists of PPAR-α and PPAR-γ in Rats

2020 ◽  
Vol 3 (2) ◽  
pp. 76-86
Author(s):  
Mahmoud M. Farag ◽  
Ehab H. Ashour ◽  
Wessam F. El-Hadidy
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Serum Insulin ◽  
Combined Treatment ◽  
Vehicle Group ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
The Metabolic Syndrome ◽  
High Fructose

Background: The use of high-fructose (Fr) corn sweeteners and sucrose in manufactured food has markedly increased recently. This excessive Fr intake has been proposed in the etiology of the metabolic syndrome, which shows an increasing prevalence throughout the world. Objective: In this study, we questioned whether fenofibrate (FF), a peroxisome proliferator-activated receptor (PPAR)-α agonist, and pioglitazone (PG), a PPAR-γ agonist, might be effective in ameliorating the metabolic syndrome in a rat model. Materials and Methods: The metabolic syndrome was induced by feeding rats a high-Fr (60%) diet for 10 weeks. The rats were divided into 5 groups: control group, fed a normal rat chow; Fr + vehicle group; Fr + FF group; Fr + PG group; and Fr + (FF + PG) group (treated with both drugs). Drug or vehicle treatment was given daily for 6 weeks (from weeks 5 to 10). Thereafter, blood and liver samples were obtained for biochemical studies. Results: Rats fed a high-Fr diet developed hyperglycemia, hyperinsulinemia, hyperuricemia, hypertriglyceri­demia, and hypercholesterolemia, and had increased serum alanine aminotransferase, hepatic tumor necrosis factor-α, and malondialdehyde levels but decreases in both glutathione content and superoxide dismutase activity. Rat treatment with FF and/or PG attenuated these alterations. The improvement was greater with the combined treatment than with either drug alone, and normalization of insulin sensitivity was observed only in rats treated with the combination therapy. Conclusion: Acting on the 2 main PPAR subfamilies, the combination of FF and PG provides a more efficacious therapy for modulating the changes in serum insulin, uric acid, and lipids, as well as the accompanying hepatic inflammation and oxidative stress that characterize the Fr-induced metabolic syndrome.

Evolution of Peroxisome Proliferator-Activated Receptor Agonists

2007 ◽  
Vol 41 (6) ◽  
pp. 973-983 ◽  
Author(s):  
Feng Chang ◽  
Linda A Jaber ◽  
Helen D Berlie ◽  
Mary Beth O'Connell
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Adverse Effects ◽  
Phase Ii ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metabolism Regulation ◽  
Ppar Γ ◽  
The Metabolic Syndrome ◽  
Phase Ii And Iii

OBJECTIVE: To discuss the evolution of peroxisome proliferator-activated receptor (PPAR) agonists from single site to multiple subtype or partial agonists for the treatment of type 2 diabetes, dyslipidemia, obesity, and the metabolic syndrome. DATA SOURCES: Information was obtained from MEDLINE (1966-March 2007) using search terms peroxisome proliferator-activated receptor agonist, PPAR dual agonist, PPAR α/γ agonist, PPAR pan agonist, partial PPAR, and the specific compound names. Other sources included pharmaceutical companies, the Internet, and the American Diabetes Association 64th-66th Scientific Sessions abstract books. STUDY SELECTION AND DATA EXTRACTION: Animal data, abstracts, clinical trials, and review articles were reviewed and summarized. DATA SYNTHESIS: PPAR α, γ, and δ receptors play an important role in lipid metabolism, regulation of adipocyte proliferation and differentiation, and insulin sensitivity. The PPAR dual agonists were developed to combine the triglyceride lowering and high-density lipoprotein cholesterol elevation from the PPAR-α agonists (fibrates) with the insulin sensitivity improvement from the PPAR-γ agonists (thiazolidinediones). Although the dual agonists reduced hemoglobin A1C(A1C) and improved the lipid profile, adverse effects led to discontinued development. Currently, PPAR-γ agonists (GW501516 in Phase I trials), partial PPAR-γ agonists (metaglidasen in Phase II and III trials), and pan agonists (α, γ, δ netoglitazone in Phase II and III trials) with improved cell and tissue selectivity are undergoing investigation to address multiple aspects of the metabolic syndrome with a single medication. By decreasing both A1C and triglycerides, metaglidasen did improve multiple aspects of the metabolic syndrome with fewer adverse effects than compared with placebo. Metaglidasen is now being compared with pioglitazone. CONCLUSIONS: Influencing the various PPARs results in improved glucose, lipid, and weight management, with effects dependent on full or partial agonist activity at single or multiple receptors. Although the dual PPAR compounds have been associated with unacceptable toxicities, new PPAR agonist medications continue to be developed and investigated to discover a safe drug with benefits in multiple disease states.

scholarly journals Effect of PPAR-γ Agonist on Adiponectin Levels in the Metabolic Syndrome: Lessons From the High Fructose Fed Rat Model

2007 ◽  
Vol 20 (2) ◽  
pp. 206-210 ◽  
Author(s):  
Y SHARABI ◽  
M ORONHERMAN ◽  
Y KAMARI ◽  
I AVNI ◽  
E PELEG ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Rat Model ◽  
Ppar Γ ◽  
The Metabolic Syndrome ◽  
High Fructose

Insulin-Leptin Axis, Cardiometabolic Risk and Oxidative Stress in Elderly with Metabolic Syndrome

2018 ◽  
Vol 126 (07) ◽  
pp. 445-452 ◽  
Author(s):  
Daniela Gradinaru ◽  
Husseina Khaddour ◽  
Denisa Margina ◽  
Anca Ungurianu ◽  
Claudia Borsa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Uric Acid ◽  
Resistance Index ◽  
Hdl Cholesterol ◽  
Elderly Subjects ◽  
Control Group ◽  
Oxidative Stress Biomarkers ◽  
The Metabolic Syndrome ◽  
And Oxidative Stress

AbstractInsulin and leptin have an overlapping anorexigenic action as well as opposite effects on glucose and lipid metabolism. The study focuses on the biochemical and clinical relevance of new indices of insulin-leptin axis utilized in the study of the relationships between leptinemia, insulin sensitivity and oxidative stress, in elderly subjects with metabolic syndrome. We conducted clinical studies on elderly people with metabolic syndrome versus control subjects by creating new insulin-adipogenic indices, namely Insulin-to-Leptin Ratio (ILR) and Insulin-Adipogenic Resistance index (IAR-index). Inflammation and oxidative stress biomarkers evaluated were the high-sensitivity C-reactive protein (hsCRP), the advanced oxidation protein products (AOPP), and the serum antioxidant capacity measured as ferric reducing antioxidant potential (FRAP). The metabolic syndrome group showed significantly (p<0.01) lower levels of ILR and not significant (p=0.09) higher values of IAR-index, as compared to the control group. In metabolic syndrome subjects, the IAR-index was significantly positively correlated with uric acid (r=0.313, p<0.05), FRAP (r=0.347, p<0.05) and AOPP (r=0.677, p<0.01), and negatively correlated with HDL-cholesterol (r=− 0.340, p<0.05) as well as with the ratio FRAP/uric acid (r=− 0.315, p<0.05). ILR and IAR-index reflected the biological state of adipose and pancreatic β-cells and seem to depict the adipo-insular axis status related to metabolic and oxidative stress better than individual markers. Therefore, ILR and IAR-index could represent integrated high-potential biomarkers for disease and patient stratification.

scholarly journals Reduced-energy cranberry juice increases folic acid and adiponectin and reduces homocysteine and oxidative stress in patients with the metabolic syndrome

2013 ◽  
Vol 110 (10) ◽  
pp. 1885-1894 ◽  
Author(s):  
Tathiana Name Colado Simão ◽  
Marcell Alysson Batisti Lozovoy ◽  
Andréa Name Colado Simão ◽  
Sayonara Rangel Oliveira ◽  
Danielle Venturini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Metabolic Syndrome ◽  
Folic Acid ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Treated Group ◽  
Control Group ◽  
Cranberry Juice ◽  
The Metabolic Syndrome

The metabolic syndrome (MetS) comprises pathological conditions that include insulin resistance, arterial hypertension, visceral adiposity and dyslipidaemia, which favour the development of CVD. Some reports have shown that cranberry ingestion reduces cardiovascular risk factors. However, few studies have evaluated the effect of this fruit in subjects with the MetS. The objective of the present study was to assess the effect of reduced-energy cranberry juice consumption on metabolic and inflammatory biomarkers in patients with the MetS, and to verify the effects of cranberry juice concomitantly on homocysteine and adiponectin levels in patients with the MetS. For this purpose, fifty-six individuals with the MetS were selected and divided into two groups: control group (n36) and cranberry-treated group (n20). After consuming reduced-energy cranberry juice (0·7 litres/d) containing 0·4 mg folic acid for 60 d, the cranberry-treated group showed an increase in adiponectin (P= 0·010) and folic acid (P= 0·033) and a decrease in homocysteine (P< 0·001) in relation to baseline values and also in comparison with the controls (P< 0·05). There was no significant change in the pro-inflammatory cytokines TNF-α, IL-1 and IL-6. In relation to oxidative stress measurements, decreased (P< 0·05) lipoperoxidation and protein oxidation levels assessed by advanced oxidation protein products were found in the cranberry-treated group when compared with the control group. In conclusion, the consumption of cranberry juice for 60 d was able to improve some cardiovascular risk factors. The present data reinforce the importance of the inverse association between homocysteine and adiponectin and the need for more specifically designed studies on MetS patients.

scholarly journals Moderate Aerobic Exercise May Reduce Metabolic Syndrome Induced Testicular Oxidative Stress and Deterioration in Sperm Parameters

2021 ◽  
pp. 38-45
Author(s):  
Muhammed Emre Karaman ◽  
Cengiz Arslan ◽  
Mehmet Ferit Gürsu ◽  
Halil Ibrahim Güngör ◽  
Gözde Arkali ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Oxidative Damage ◽  
Aerobic Exercise ◽  
The Other ◽  
Sperm Parameters ◽  
Moderate Intensity ◽  
Control Group ◽  
Albino Rats ◽  
The Metabolic Syndrome

Aims: Studies on testicular oxidative stress, sperm density, motility and morphology of exercise applications in the case of metabolic syndrome is limited. In the present study, it was aimed to investigate the effects of aerobic and anaerobic exercise applications on sperm parameters and testicular oxidative stress parameters in metabolic syndrome induced rats. Study Design:  Controlled Trial. Place and Duration of Study: Firat University Experimental Research Center, Elazığ/Turkey. Methodology: A total of 24 male Wistar-Albino rats were used in the study. For inducing the metabolic syndrome, 30% fructose solution was prepared fresh every day and administered ad-libitum through the drinking water of the animals. The rats were divided into 4 groups (G1: Control, G2: Metabolic Syndrome, G3: Metabolic Syndrome + Aerobic Ex., G4: Metabolic Syndrome + Anaerobic Ex.). Exercise practices continued 3 days in a week for 6 weeks. Results: Sperm concentrations of G2 and G4 were statistically significantly lower than the control group. The abnormality percentage of G4 was statistically significantly higher than the other groups in terms of head abnormality and total abnormality. MDA level of G2 was statistically significantly higher than the other groups, while GSHpx and catalase levels were low. Conclusion: It can be said that metabolic syndrome may cause oxidative damage in testicular tissue and deterioration in sperm parameters. Moderate-intensity aerobic exercise reduces the deterioration in sperm parameters by creating a protective response against oxidative damage.

scholarly journals Effect of n-3 PUFA supplementation at different EPA:DHA ratios on the spontaneously hypertensive obese rat model of the metabolic syndrome

2015 ◽  
Vol 113 (6) ◽  
pp. 878-887 ◽  
Author(s):  
Eunice Molinar-Toribio ◽  
Jara Pérez-Jiménez ◽  
Sara Ramos-Romero ◽  
Marta Romeu ◽  
Montserrat Giralt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Metabolic Syndrome ◽  
Control Group ◽  
Cvd Risk ◽  
Prediabetic State ◽  
Pufa Supplementation ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
The Metabolic Syndrome

The increasing incidence of the metabolic syndrome (MetS), a combination of risk factors before the onset of CVD and type 2 diabetes, encourages studies on the role of functional food components such as long-chain n-3 PUFA as preventive agents. In the present study, we explore the effect of EPA and DHA supplementation in different proportions on spontaneously hypertensive obese (SHROB) rats, a model for the MetS in a prediabetic state with mild oxidative stress. SHROB rats were randomised into four groups (n 7), each supplemented with EPA/DHA at ratios of 1:1, 2:1 and 1:2, or soyabean oil as the control for 13 weeks. The results showed that in all the proportions tested, EPA/DHA supplementation significantly lowered total and LDL-cholesterol concentrations, compared with those of the control group. EPA/DHA supplementation at the ratios of 1:1 and 2:1 significantly decreased inflammation (C-reactive protein levels) and lowered oxidative stress (decreased excretion of urinary isoprostanes), mainly at the ratio of 1:2. The activity of antioxidant enzymes increased in erythrocytes, abdominal fat and kidneys, with magnitudes depending on the EPA:DHA ratio. PUFA mixtures from fish affected different MetS markers of CVD risk factors in SHROB rats, depending on the ratios of EPA/DHA supplementation. The activation of endogenous defence systems may be related to the reduction of inflammation and oxidative stress.

scholarly journals Flax oil-mediated activation of PPAR-γ correlates with reduction of hepatic lipid accumulation in obese spontaneously hypertensive/NDmcr-cp rats, a model of the metabolic syndrome

2010 ◽  
Vol 104 (9) ◽  
pp. 1313-1321 ◽  
Author(s):  
Kanta Chechi ◽  
Naomi Yasui ◽  
Katsumi Ikeda ◽  
Yukio Yamori ◽  
Sukhinder K. Cheema
Keyword(s):  
Metabolic Syndrome ◽  
Genetic Model ◽  
Serum Insulin ◽  
Fatty Acid Content ◽  
Spontaneously Hypertensive ◽  
Hepatic Lipid ◽  
Flax Oil ◽  
Ppar Γ ◽  
The Metabolic Syndrome ◽  
Obese Rats

Flax oil feeding has been proposed to have beneficial effects on the outcome of the metabolic syndrome due to the high n-3 fatty acid content of flax oil; however, the mechanisms of its action remain largely unknown. We investigated the effects of flax oil feeding on hyperlipidaemia, hyperglycaemia, hepatic steatosis and oxidative stress in the spontaneously hypertensive (SHR)/NDmcr-cp rats, a genetic model of the metabolic syndrome. Hepatic gene expression of PPAR-α, PPAR-γ and sterol-regulatory element-binding protein-1c was also assessed in order to investigate the possible underlying mechanisms. Obese and lean SHR/NDmcr-cp rats were fed high-fat diets enriched with either lard or flax oil for a period of 4 weeks. Obese rats exhibited higher body weight, liver weight and mesenteric fat-, epididymal fat- and renal fat-pad weights, and also TAG and cholesterol concentrations in serum and VLDL, LDL and HDL fractions, when compared with the lean rats (P < 0·001), irrespective of the diets. Concentrations of fasting serum insulin and urinary thiobarbituric acid reactive substances were lower in flax oil-fed obese (FO) rats compared with the lard-fed obese (LO) rats (P < 0·01). Flax oil feeding also revealed a significant reduction in hepatic TAG and cholesterol concentrations in obese rats compared with the LO rats (P < 0·05). In addition, FO rats exhibited significantly higher hepatic mRNA expression of PPAR-γ, which negatively correlated (r − 0·98, P < 0·05) with their hepatic lipid levels. These findings suggest that flax oil feeding may activate PPAR-γ-dependent pathways to alter the hepatic lipid metabolism and to increase insulin sensitivity in the obese SHR/NDmcr-cp rats.

Fructose: a highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome

2010 ◽  
Vol 299 (5) ◽  
pp. E685-E694 ◽  
Author(s):  
Mark J. Dekker ◽  
Qiaozhu Su ◽  
Chris Baker ◽  
Angela C. Rutledge ◽  
Khosrow Adeli
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Hepatic Steatosis ◽  
Expression Patterns ◽  
Metabolic Effects ◽  
Leptin Resistance ◽  
Peroxisome Proliferator ◽  
The Metabolic Syndrome ◽  
High Fructose ◽  
The Brain

As dietary exposure to fructose has increased over the past 40 years, there is growing concern that high fructose consumption in humans may be in part responsible for the rising incidence of obesity worldwide. Obesity is associated with a host of metabolic challenges, collectively termed the metabolic syndrome. Fructose is a highly lipogenic sugar that has profound metabolic effects in the liver and has been associated with many of the components of the metabolic syndrome (insulin resistance, elevated waist circumference, dyslipidemia, and hypertension). Recent evidence has also uncovered effects of fructose in other tissues, including adipose tissue, the brain, and the gastrointestinal system, that may provide new insight into the metabolic consequences of high-fructose diets. Fructose feeding has now been shown to alter gene expression patterns (such as peroxisome proliferator-activated receptor-γ coactivator-1α/β in the liver), alter satiety factors in the brain, increase inflammation, reactive oxygen species, and portal endotoxin concentrations via Toll-like receptors, and induce leptin resistance. This review highlights recent findings in fructose feeding studies in both human and animal models with a focus on the molecular and biochemical mechanisms that underlie the development of insulin resistance, hepatic steatosis, and the metabolic syndrome.

Cut off value of plasma 25-hydroxyvitamin D concentration for predicting metabolic syndrome

2019 ◽  
pp. 68-73
Author(s):  
Trong Nghia Nguyen ◽  
Thi Nhan Nguyen ◽  
Thi Dua Dao
Keyword(s):  
Metabolic Syndrome ◽  
Medical Center ◽  
Cross Sectional Study ◽  
Control Group ◽  
Cross Sectional ◽  
Hydroxyvitamin D ◽  
The Metabolic Syndrome ◽  
25 Hydroxyvitamin D ◽  
Key Words Metabolic Syndrome ◽  
And Control

Background: The metabolic syndrome is a constellation of cardiometabolic risk factors that tend to cluster together in affected individuals more often than predicted by chance. The presence of the metabolic syndrome substantially increases the risk of developing type 2 diabetes and cardiovascular disease, and is associated with a range of adverse clinical outcomes, many of which are closely associated with aging. Current estimates suggest that approximately 20 - 25% of the world’s population is affected by the metabolic syndrome. The prevalence of the metabolic syndrome rises with age and more than 45% of people aged over 60 years have the metabolic syndrome. Recent studies show that low vitamin D status is very common in the world and this is a risk factor of metabolic syndrome. Objective: (1) Plasma 25-hydroxyvitamin D concentration in subjects with metabolic syndrome. (2) Cut off value of plasma 25-hydroxyvitamin D concentration for predicting metabolic syndrome. Material and method: A cross-sectional study with control group on 318 adult subjects for health examinations at International Medical Center at Hue Central Hospital, including 139 subjects with metabolic syndrome and control group of 179 healthy subjects. Metabolic syndrome was defined according to the IDF, NHLBI, AHA, WHF, IAS, IASO (2009). Plasma hydroxyvitamin D concentration was measured using chemiluminescent microparticle immunoassay. Reciever operating characteristic (ROC) curve were generated to assess sensitivity and specificity for different cut off value of 25-hydroxyvitamin D concentration for predicting metabolic syndrome. Results: Plasma 25-hydroxyvitamin D concentration in subjects with metabolic syndrome was 26.4 ng/ml, incidence of plasma 25-hydroxyvitamin D deficiency (59.7%) was significantly higher than in control group (23.5%) (p < 0.001). The optimal cut off point for 25-OH-D concentration for predictor of metabolic syndrome as 26.4 ng/ml (AUC=0.657, sensitivity=53.4%, specificity=71.6%). Conclusion: In 139 subjects with metabolic syndrome, the plasma 25-hydroxyvitamin D concentration was 26.4 ng/ml and the incidence of 25-hydroxyvitamin D deficiency in the metabolic syndrome group was 59.7%. The optimal cut off point for plasma 25-hydroxyvitamin D concentration for predictor of metabolic syndrome as 26.4 ng/ml. Key words: Metabolic syndrome, 25-hydroxyvitamin D

Effect of Opuntia dejecta (Salm-Dyck) flowers in liver of fructose-fed rats: Biochemicals, enzymatic and histological studies

2021 ◽  
pp. 096032712110134
Author(s):  
O Zouaoui ◽  
K Adouni ◽  
A Jelled ◽  
A Thouri ◽  
A Ben Chrifa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Body Weight ◽  
Diabetes Type 2 ◽  
Male Rats ◽  
Control Group ◽  
Standard Drug ◽  
High Fructose ◽  
Group A ◽  
Histological Architecture

Phytochemical composition and antioxidant activity of flowers decoction at post-flowering stage (F3D) of Opuntia dejecta were determined. The obtained findings demonstrate that F3D has a marked antioxidant activity in all tested assays. Furthermore, the present study was designed to test the protective activity of F3D against induced Diabetes type 2 (DT2) in male rats. Those metabolic syndromes were induced by a high-fructose diet (HFD) (10% fructose solution) for a period of 20 weeks. F3D was administered orally (100 and 300 mg/kg body weight) daily for the last 4 weeks. Metformin (150 mg/kg body weight) was used as a standard drug and administrated orally for the last 4 weeks. The results showed a significant increase in blood glucose, triglycerides and hepatic markers (ALAT, ASAT and ALK-P) in HFD group. A significant increase in hepatic TBARS and a significant decrease in SOD, CAT and GPX were observed in fructose fed rats compared to control group. Administration of F3D showed a protective effect in biochemical and oxidative stress parameters measured in this study. Also, oral administration of F3D restored the histological architecture of rat liver in comparison with rats fed HFD. In conclusion, F3D attenuated hepatic oxidative stress in fructose-fed rats.

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