scholarly journals Nitrooleic Acid Attenuates Lipid Metabolic Disorders and Liver Steatosis in DOCA-Salt Hypertensive Mice

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Haiping Wang ◽  
Jing Sun ◽  
Zhanjun Jia ◽  
Tianxin Yang ◽  
Liang Xu ◽  
...  
Keyword(s):  
Liver Lipid ◽  
Liver Steatosis ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Mice Model ◽  
Nonesterified Fatty Acids ◽  
Liver Lipid Content ◽  
Beneficial Effects ◽  
Cholesterol Levels ◽  
Peroxisome Proliferator Activated Receptors

Nitrooleic acid (OA-NO2) is endogenous ligands for peroxisome proliferator-activated receptors. The present study was aimed at investigating the beneficial effects of OA-NO2on the lipid metabolism and liver steatosis in deoxycorticosterone acetate- (DOCA-) salt induced hypertensive mice model. Male C57BL/6 mice were divided to receive DOCA-salt plus OA-NO2or DOCA-salt plus vehicle and another group received neither DOCA-salt nor OA-NO2(control group). After 3-week treatment with DOCA-salt plus 1% sodium chloride in drinking fluid, the hypertension was noted; however, OA-NO2had no effect on the hypertension. In DOCA-salt treated mice, the plasma triglyceride and total cholesterol levels were significantly increased compared to control mice, and pretreatment with OA-NO2significantly reduced these parameters. Further, the histopathology of liver exhibited more lipid distribution together with more serious micro- and macrovesicular steatosis after DOCA-salt treatment and that was consistent with liver tissue triglyceride and nonesterified fatty acids (NEFA) content. The mice pretreated with OA-NO2showed reduced liver damage accompanied with low liver lipid content. Moreover, the liver TBARS, together with the expressions of gp91phox and p47phox, were parallelly decreased. These findings indicated that OA-NO2had the protective effect on liver injury against DOCA-salt administration and the beneficial effect could be attributed to its antihyperlipidemic activities.

scholarly journals Impact of flaxseed intake upon metabolic syndrome indicators in female Wistar rats

2012 ◽  
Vol 27 (8) ◽  
pp. 537-543 ◽  
Author(s):  
Lívia Hipólito Cardozo Brant ◽  
Ludmila Ferreira Medeiros de França Cardozo ◽  
Luís Guillermo Coca Velarde ◽  
Gilson Teles Boaventura
Keyword(s):  
Metabolic Syndrome ◽  
Body Weight ◽  
Body Weight Gain ◽  
Control Group ◽  
Lactation Period ◽  
Pregnant Rats ◽  
Beneficial Effects ◽  
Cholesterol Levels ◽  
Female Wistar Rats ◽  
Glucose Profiles

PURPOSE: To evaluate whether the prolonged consumption of flaxseed minimize the factors that trigger MS in healthy rats. METHODS: Pregnant rats were divided immediately after delivery into two groups during the lactation period, a control group (CG) receiving casein-based diet with 17% of protein, and a Flaxseed group (FG) with casein-based diet plus 25% of flaxseed. At weaning, 12 offspring of each group continued to receive the same feed but with 10% of protein up to 200 days old. RESULTS: FG showed a significant reduction in body weight (p=0.001), total cholesterol levels (p<0.0001), triglycerides (p=0.0001), and glucose (p=0.001). CONCLUSION: The flaxseed alters the indicators related to development of metabolic syndrome, because it has beneficial effects on lipids and glucose profiles and prevents the excess of body weight gain.

GLP-1-mediated delivery of the PPAR𝛼/𝛾 dual-agonist Tesaglitazar improves obesity and glucose metabolism in mice

2021 ◽  
Author(s):  
Carmelo Quarta ◽  
Kerstin Stemmer ◽  
Aaron Novikoff ◽  
Bin Yang ◽  
Felix Klingelhuber ◽  
...  
Keyword(s):  
Body Weight ◽  
Glucose Metabolism ◽  
Peroxisome Proliferator ◽  
Protein Targets ◽  
Beneficial Effects ◽  
Glucose And Lipid Metabolism ◽  
Therapeutic Value ◽  
Affect Body Weight ◽  
Peroxisome Proliferator Activated Receptors ◽  
Dual Agonist

Abstract Dual-agonists activating the peroxisome proliferator-activated receptors alpha and gamma (PPAR𝛼/𝛾) have shown beneficial effects on glucose and lipid metabolism in patients with type 2 diabetes, but their development was discontinued due to unfavorable cardiovascular and/or renal effects. Here we report the design and preclinical evaluation of a molecule that covalently links the PPAR𝛼/𝛾 dual-agonist Tesaglitazar to GLP-1 to allow for the GLP-1 receptor-dependent delivery of Tesaglitazar. GLP-1/Tesaglitazar does not differ from matched GLP-1 in GLP-1R signaling, but shows GLP-1R-dependent PPAR𝛾-RXR heterodimerization with enhanced efficacy to improve body weight, food intake, and glucose metabolism relative to GLP-1 or Tesaglitazar in mice with diet- and genetically-induced obesity. The conjugate fails to affect body weight and glucose metabolism in GLP-1R knockout (ko) mice and shows preserved effects in DIO mice at doses subthreshold for GLP-1 and Tesaglitazar to improve metabolism. Consistent with the GLP-1R expression pattern, LC/MS-based proteomics identified a series of novel PPAR protein targets in the hypothalamus that are acutely upregulated by Tesaglitazar and by GLP-1/Tesaglitazar, but not by treatment with GLP-1. Collectively, our data show that GLP-1/Tesaglitazar improves energy and glucose metabolism with superior efficacy to GLP-1 or Tesaglitazar alone and suggest that this conjugate holds therapeutic value to treat hyperglycemia and insulin resistance.

scholarly journals Beneficial Effects of Newly Isolated Akkermansia muciniphila Strains from the Human Gut on Obesity and Metabolic Dysregulation

2020 ◽  
Vol 8 (9) ◽  
pp. 1413
Author(s):  
Meng Yang ◽  
Shambhunath Bose ◽  
Sookyoung Lim ◽  
JaeGu Seo ◽  
JooHyun Shin ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Intestinal Inflammation ◽  
Body Weight Gain ◽  
Liver Steatosis ◽  
Caloric Intake ◽  
Hepatic Function ◽  
Low Grade ◽  
Mice Model ◽  
Akkermansia Muciniphila ◽  
Beneficial Effects

The identification of new probiotics with anti-obesity properties has attracted considerable interest. In the present study, the anti-obesity activities of Akkermansia muciniphila (A. muciniphila) strains isolated from human stool samples and their relationship with the gut microbiota were evaluated using a high fat-diet (HFD)-fed mice model. Three strains of A. muciniphila were chosen from 27 isolates selected based on their anti-lipogenic activity in 3T3-L1 cells. The anti-lipogenic, anti-adipogenic and anti-obesity properties of these three strains were evaluated further in HFD-induced obese mice. The animals were administered these strains six times per week for 12 weeks. The treatment improved the HFD-induced metabolic disorders in mice in terms of the prevention of body weight gain, caloric intake and reduction in the weights of the major adipose tissues and total fat. In addition, it improved glucose homeostasis and insulin sensitivity. These effects were also associated with the inhibition of low-grade intestinal inflammation and restoration of damaged gut integrity, prevention of liver steatosis and improvement of hepatic function. These results revealed a difference in the distribution pattern of the gut microbial communities between groups. Therefore, the gut microbial population modulation, at least in part, might contribute to the beneficial impact of the selected A. muciniphila strains against metabolic disorders.

Prenatal androgen excess alters the uterine peroxisome proliferator-activated receptor (PPAR) system

2019 ◽  
Vol 31 (8) ◽  
pp. 1401
Author(s):  
Silvana R. Ferreira ◽  
Leandro M. Vélez ◽  
Maria F. Heber ◽  
Giselle A. Abruzzese ◽  
Alicia B. Motta
Keyword(s):  
Fetal Programming ◽  
Female Offspring ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Androgen Excess ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peroxisome Proliferator Activated Receptors ◽  
Pg E2 ◽  
Prenatal Androgen

It is known that androgen excess induces changes in fetal programming that affect several physiological pathways. Peroxisome proliferator-activated receptors (PPARs) α, δ and γ are key mediators of female reproductive functions, in particular in uterine tissues. Thus, we aimed to study the effect of prenatal hyperandrogenisation on the uterine PPAR system. Rats were treated with 2mg testosterone from Day 16 to 19 of pregnancy. Female offspring (PH group) were followed until 90 days of life, when they were killed. The PH group exhibited an anovulatory phenotype. We quantified uterine mRNA levels of PPARα (Ppara), PPARδ (Ppard), PPARγ (Pparg), their regulators peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Ppargc1a) and nuclear receptor co-repressor 1 (Ncor1) and cyclo-oxygenase (COX)-2 (Ptgs2), and assessed the lipid peroxidation (LP) index and levels of glutathione (GSH) and prostaglandin (PG) E2. The PH group showed decreased levels of all uterine PPAR isoforms compared with the control group. In addition, PGE2 and Ptgs2 levels were increased in the PH group, which led to a uterine proinflammatory environment, as was LP, which led to a pro-oxidant status that GSH was not able to compensate for. These results suggest that prenatal exposure to androgen excess has a fetal programming effect that affects the gene expression of PPAR isoforms, and creates a misbalanced oxidant–antioxidant state and a proinflammatory status.

Thermal acclimation in Antarctic fish: transcriptomic profiling of metabolic pathways

2011 ◽  
Vol 301 (5) ◽  
pp. R1453-R1466 ◽  
Author(s):  
Heidrun Sigrid Windisch ◽  
Raphaela Kathöver ◽  
Hans-Otto Pörtner ◽  
Stephan Frickenhaus ◽  
Magnus Lucassen
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Citrate Synthase ◽  
Thermal Sensitivity ◽  
Antarctic Fish ◽  
Control Group ◽  
Acclimation Temperature ◽  
Peroxisome Proliferator ◽  
Warm Acclimation ◽  
Peroxisome Proliferator Activated Receptors ◽  
Large Rearrangements

It is widely accepted that adaptation to the extreme cold has evolved at the expense of high thermal sensitivity. However, recent studies have demonstrated significant capacities for warm acclimation in Antarctic fishes. Here, we report on hepatic metabolic reorganization and its putative molecular background in the Antarctic eelpout ( Pachycara brachycephalum ) during warm acclimation to 5°C over 6 wk. Elevated capacities of cytochrome c oxidase suggest the use of warm acclimation pathways different from those in temperate fish. The capacity of this enzyme rose by 90%, while citrate synthase (CS) activity fell by 20% from the very beginning. The capacity of lipid oxidation by hydroxyacyl-CoA dehydrogenase remained constant, whereas phosphoenolpyruvate carboxykinase as a marker for gluconeogenesis displayed 40% higher activities. These capacities in relation to CS indicate a metabolic shift from lipid to carbohydrate metabolism. The finding was supported by large rearrangements of the related transcriptome, both functional genes and potential transcription factors. A multivariate analysis (canonical correspondence analyses) of various transcripts subdivided the incubated animals in three groups, one control group and two responding on short and long timescales, respectively. A strong dichotomy in the expression of peroxisome proliferator-activated receptors-1α and -β receptors was most striking and has not previously been reported. Altogether, we identified a molecular network, which responds sensitively to warming beyond the realized ecological niche. The shift from lipid to carbohydrate stores and usage may support warm hardiness, as the latter sustain anaerobic metabolism and may prepare for hypoxemic conditions that would develop upon warming beyond the present acclimation temperature.

scholarly journals PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric population

2020 ◽  
Author(s):  
Karina Vargas-Sánchez ◽  
Laura Vargas ◽  
Yenny Urrutia ◽  
Iván Beltrán ◽  
Ana Beatriz Rossi ◽  
...  
Keyword(s):  
Pediatric Obesity ◽  
Pediatric Population ◽  
Fat Distribution ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Tnf Α ◽  
Android Fat ◽  
Glucagon Like Peptide 1 ◽  
Peroxisome Proliferator Activated Receptors ◽  
Inflammatory Profile

Abstract Background: Obesity configures a pathophysiological profile that predisposes the development of metabolic and cardiovascular diseases, critically impacting public health. The chronic dysregulation of immuno-metabolic components triggered by pediatric obesity is a common but scarcely understood aspect of the disease. Peroxisome proliferator-activated receptors (PPARs) are a group of transcription factors essential for energy and immune homeostasis of different tissues. Besides, the glucagon-like peptide-1 receptor (GLP-1R) activation influences insulin secretion, but also regulates the cytokine profile possibly mediated through a PPAR isotype. However, the role of PPARs and GLP-1R in leukocytes from obese pediatric patients remains unclear. Therefore, we examined the expression of PPARs isotypes and GLP-1R in leukocytes, and its correlation with metabolic, hormonal, inflammatory, and anthropometric markers in an obese pediatric population.Results: Obese children and adolescents presented a significant increase in anthropometric and body composition parameters, TG, VLDL, TG/HDL, android fat (%)/gynoid fat (%) (A/G%) index, and HOMA score when compared with the control group. Obese participants exhibited a pro-inflammatory profile with an augment of IL-8 (p=0,0081), IL-6 (p=0,0005), TNF-α (p=0,0004), IFN-γ (p=0,0110), MCP-1 (p=0,0452), and adipsin (p=0,0397), whereas displayed a reduction of adiponectin (p=0,0452). The expression of PPARα and GLP-1R was lower in the leukocytes from obese participants than in lean subjects. Furthermore, PPARα correlates negatively with TNF-α (p=0,0383), while GLP-1R did not show correlation with any inflammatory variable. However, both receptors correlate negatively with the abdominal skinfold. Although PPARβ/δ expression was similar between groups, it was negatively associated with IL-8 levels (p=0,0085).Conclusions: PPARα and PPARβ/δ expression are negatively correlated with the proinflammatory markers TNF-α and IL-8, respectively, suggesting participation in the regulation of inflammation which was observed to be altered in pediatric obesity. Furthermore, PPARα and GLP-1R are downregulated in leukocytes from obese participants. The low expression of both receptors is correlated with an increase in abdominal skinfold, suggesting a role in fat distribution that could indirectly affect cytokine secretion from different immune and adipose cells, likely triggering an inflammatory profile as a consequence of obesity. Altogether, these findings may impact the understanding and implementation of PPARα or GLP-1R agonists in the clinic.

scholarly journals Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 571 ◽  
Author(s):  
Tapan Behl ◽  
Aditi Sharma ◽  
Lalit Sharma ◽  
Aayush Sehgal ◽  
Gokhan Zengin ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Biological Activities ◽  
Modern Science ◽  
Withaferin A ◽  
Antidiabetic Activity ◽  
Peroxisome Proliferator ◽  
Cancer Hallmarks ◽  
Beneficial Effects ◽  
Therapeutic Outcomes ◽  
Peroxisome Proliferator Activated Receptors

Withaferin A (WA), a manifold studied, C28-steroidal lactone withanolide found in Withania somnifera. Given its unique beneficial effects, it has gathered attention in the era of modern science. Cancer, being considered a “hopeless case and the leading cause of death worldwide, and the available conventional therapies have many lacunae in the form of side effects. The poly pharmaceutical natural compound, WA treatment, displayed attenuation of various cancer hallmarks by altering oxidative stress, promoting apoptosis, and autophagy, inhibiting cell proliferation, reducing angiogenesis, and metastasis progression. The cellular proteins associated with antitumor pathways were also discussed. WA structural modifications attack multiple signal transduction pathways and enhance the therapeutic outcomes in various diseases. Moreover, it has shown validated pharmacological effects against multiple neurodegenerative diseases by inhibiting acetylcholesterinases and butyrylcholinesterases enzyme activity, antidiabetic activity by upregulating adiponectin and preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ), cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis. The current review is an extensive survey of various WA associated disease targets, its pharmacokinetics, synergistic combination, modifications, and biological activities.

scholarly journals Resveratrol and Quercetin as Regulators of Inflammatory and Purinergic Receptors to Attenuate Liver Damage Associated to Metabolic Syndrome

2021 ◽  
Vol 22 (16) ◽  
pp. 8939
Author(s):  
Agustina Cano-Martínez ◽  
Rocío Bautista-Pérez ◽  
Vicente Castrejón-Téllez ◽  
Elizabeth Carreón-Torres ◽  
Israel Pérez-Torres ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Damage ◽  
Purinergic Receptor ◽  
Critical Role ◽  
Hepatocyte Proliferation ◽  
Peroxisome Proliferator ◽  
Ppar Alpha ◽  
Nonalcoholic Fatty Liver ◽  
Beneficial Effects ◽  
Peroxisome Proliferator Activated Receptors

Nonalcoholic fatty liver disease (NAFLD) is considered a manifestation of metabolic syndrome (MS) and is characterized by the accumulation of triglycerides and a varying degree of hepatic injury, inflammation, and repair. Moreover, peroxisome-proliferator-activated receptors (PPARs) play a critical role in the pathophysiological processes in the liver. There is extensive evidence of the beneficial effect of polyphenols such as resveratrol (RSV) and quercetin (QRC) on the treatment of liver pathology; however, the mechanisms underlying their beneficial effects have not been fully elucidated. In this work, we show that the mechanisms underlying the beneficial effects of RSV and QRC against inflammation in liver damage in our MS model are due to the activation of novel pathways which have not been previously described such as the downregulation of the expression of toll-like receptor 4 (TLR4), neutrophil elastase (NE) and purinergic receptor P2Y2. This downregulation leads to a decrease in apoptosis and hepatic fibrosis with no changes in hepatocyte proliferation. In addition, PPAR alpha and gamma expression were altered in MS but their expression was not affected by the treatment with the natural compounds. The improvement of liver damage by the administration of polyphenols was reflected in the normalization of serum transaminase activities.

scholarly journals Peroxisome Proliferator-Activated Receptors Family Is Involved in the Response to Treatment and Mild Clinical Course in Patients with Ulcerative Colitis

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
J. K. Yamamoto-Furusho ◽  
M. Jacintez-Cazares ◽  
J. Furuzawa-Carballeda ◽  
G. Fonseca-Camarillo
Keyword(s):  
Gene Expression ◽  
Intestinal Inflammation ◽  
Clinical Course ◽  
Combined Therapy ◽  
Response To Treatment ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
High Gene Expression ◽  
High Gene ◽  
Peroxisome Proliferator Activated Receptors

Background. PPARs play an important role in the regulation of intestinal inflammation.Methods. We included a total of 46 UC patients and 31 controls. The gene expression of PPARs was measured by RT-PCR and protein expression by immunohistochemistry.Results. PPARαgene expression was significantly decreased in patients with active UC compared with remission UC group(P=0.001)and controls(P=0.001). We found that low gene expression of PPARαin mucosa confers a higher risk of UC activity (P≤0.0001, OR = 22.6). We observed an increase of PPARαexpression in patients with UC who were treated with 5-aminosalicylates compared with those who received any other combined therapy (P=0.03, OR = 0.08). PPARγgene expression was decreased in the active UC group compared with UC in remission(P=0.001)and control group(P=0.001). An increased expression of PPARγgene was associated with mild clinical course of the disease (P≤0.001, OR = 0.05). No gene expression of PPARβ/δwas found in the colonic mucosa from UC patients and controls.Conclusion. Our results suggest that patients with high gene expression of PPARs have a better response to medical treatment and a mild clinical course of the disease.

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