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 CRISPR-mediated BMP9 ablation promotes liver steatosis via the down-regulation of PPARα expression

2020 ◽  
Vol 6 (48) ◽  
pp. eabc5022
Author(s):  
Z. Yang ◽  
P. Li ◽  
Q. Shang ◽  
Y. Wang ◽  
J. He ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Critical Role ◽  
Liver Steatosis ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Triglyceride Accumulation

Obesity drives the development of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis. Several bone morphogenetic proteins (BMPs) except BMP9 were reported related to metabolic syndrome. This study demonstrates that liver cytokine BMP9 is decreased in the liver and serum of NAFLD model mice and patients. BMP9 knockdown induces lipid accumulation in Hepa 1-6 cells. BMP9–knockout mice exhibit hepatosteatosis due to down-regulated peroxisome proliferator–activated receptor α (PPARα) expression and reduced fatty acid oxidation. In vitro, recombinant BMP9 treatment attenuates triglyceride accumulation by enhancing PPARα promoter activity via the activation of p-smad. PPARα-specific antagonist GW6471 abolishes the effect of BMP9 knockdown. Furthermore, adeno-associated virus–mediated BMP9 overexpression in mouse liver markedly relieves liver steatosis and obesity-related metabolic syndrome. These findings indicate that BMP9 plays a critical role in regulating hepatic lipid metabolism in a PPARα-dependent manner and may provide a previously unknown insight into NAFLD therapeutic approaches.

scholarly journals Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 185
Author(s):  
Clara Depommier ◽  
Rosa Maria Vitale ◽  
Fabio Arturo Iannotti ◽  
Cristoforo Silvestri ◽  
Nicolas Flamand ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Univariate Analysis ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Akkermansia Muciniphila ◽  
Beneficial Effects ◽  
Daily Ingestion ◽  
Before And After ◽  
Palmitoyl Glycerol

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.

scholarly journals Genetic Polymorphisms in the HTR2C and Peroxisome Proliferator-Activated Receptors Are Not Associated with Metabolic Syndrome in Patients with Schizophrenia Taking Clozapine

2011 ◽  
Vol 8 (3) ◽  
pp. 262 ◽  
Author(s):  
Shi Hyun Kang ◽  
Jong Il Lee ◽  
An Kee Chang ◽  
Yeon Ho Joo ◽  
Chang Yoon Kim ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Genetic Polymorphisms ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors

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 Peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms in nonalcoholic fatty liver disease: A study in Brazilian patients

Gene ◽  
2013 ◽  
Vol 529 (2) ◽  
pp. 326-331 ◽  
Author(s):  
Fernanda Aparecida Domenici ◽  
Maria José Franco Brochado ◽  
Ana de Lourdes Candolo Martinelli ◽  
Sergio Zucoloto ◽  
Selma Freire de Carvalho da Cunha ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Peroxisome Proliferator ◽  
Nonalcoholic Fatty Liver ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals The Epidemiology, Risk Profiling and Diagnostic Challenges of Nonalcoholic Fatty Liver Disease

Medicines ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. 41 ◽  
Author(s):  
Umair Iqbal ◽  
Brandon Perumpail ◽  
Daud Akhtar ◽  
Donghee Kim ◽  
Aijaz Ahmed
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
High Risk ◽  
Environmental Factors ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Active Management ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver damage from the more prevalent (75%–80%) and nonprogressive nonalcoholic fatty liver (NAFL) category to its less common and more ominous subset, nonalcoholic steatohepatitis (NASH). NAFLD is now the most common cause of chronic liver disease in the developed world and is a leading indication for liver transplantation in United States (US). The global prevalence of NAFLD is estimated to be 25%, with the lowest prevalence in Africa (13.5%) and highest in the Middle East (31.8%) and South America (30.4%). The increasing incidence of NAFLD has been associated with the global obesity epidemic and manifestation of metabolic complications, including hypertension, diabetes, and dyslipidemia. The rapidly rising healthcare and economic burdens of NAFLD warrant institution of preventative and treatment measures in the high-risk sub-populations in an effort to reduce the morbidity and mortality associated with NAFLD. Genetic, demographic, clinical, and environmental factors may play a role in the pathogenesis of NAFLD. While NAFLD has been linked with various genetic variants, including PNPLA-3, TM6SF2, and FDFT1, environmental factors may predispose individuals to NAFLD as well. NAFLD is more common in older age groups and in men. With regards to ethnicity, in the US, Hispanics have the highest prevalence of NAFLD, followed by Caucasians and then African-Americans. NAFLD is frequently associated with the components of metabolic syndrome, such as type 2 diabetes mellitus (T2DM), obesity, hypertension, and dyslipidemia. Several studies have shown that the adoption of a healthy lifestyle, weight loss, and pro-active management of individual components of metabolic syndrome can help to prevent, retard or reverse NAFLD-related liver damage. Independently, NAFLD increases the risk of premature cardiovascular disease and associated mortality. For this reason, a case can be made for screening of NAFLD to facilitate early diagnosis and to prevent the hepatic and extra-hepatic complications in high risk sub-populations with morbid obesity, diabetes, and other metabolic risk factors.

A novel dual peroxisome proliferator-activated receptors α and γ agonist with beneficial effects on insulin resistance and lipid metabolism

2006 ◽  
Vol 28 (12) ◽  
pp. 863-868 ◽  
Author(s):  
Cheng Xu ◽  
Li-Li Wang ◽  
Hong-Ying Liu ◽  
Cheng-Mai Ruan ◽  
Xing-Bo Zhou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Peroxisome Proliferator ◽  
Beneficial Effects ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals Screening of Peroxisome Proliferator-activated Receptors (PPARs) α, γ and δ Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-ethnic Malaysian Population

2015 ◽  
Vol 25 (4) ◽  
pp. 383 ◽  
Author(s):  
Phee-Phee Chia ◽  
Sook-Ha Fan ◽  
Yee-How Say
Keyword(s):  
Metabolic Syndrome ◽  
Demographic Data ◽  
Plasma Lipid ◽  
Peroxisome Proliferator ◽  
Nucleotide Polymorphisms ◽  
Ethnic Population ◽  
Single Nucleotide ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ethnic Chinese ◽  
Peroxisome Proliferator Activated Receptors

<p class="Pa7"><strong>Objective: </strong>This study aimed to investigate the association of peroxisome proliferator-activated receptor (PPAR) genes <em>PPAR</em>α L162V, <em>PPAR</em><em>γ</em><em>2 </em>C161T and <em>PPAR</em><em>δ </em>T294C single nucleotide polymorphisms (SNPs) with obesity and metabolic syndrome (Met- S) in a multi-ethnic population in Kampar, Malaysia.</p><p class="Pa7"><strong>Methods: </strong>Socio-demographic data, anthropometric and biochemical measure­ments (plasma lipid profile, adiponectin and interleukin-6 [IL-6] levels) were taken from 307 participants (124 males; 180 obese; 249 Met-S; 97 Malays, 85 ethnic Chinese, 55 ethnic Indians).</p><p class="Pa7"><strong>Results: </strong>The overall minor allele frequen­cies were .08, .22 and .30 for <em>PPAR </em>α L162V, γ C161T, δ T294C, respectively. All SNPs were not associated with obesity, Met-S and obesity with/without Met-S by χ2 analysis, ethnicity-stratified and logistic re­gression analyses. Nevertheless, participants with V162 allele of <em>PPAR</em><em>α </em>had significantly higher IL-6, while those with T161 allele of <em>PPAR</em><em>γ</em><em>2 </em>had significantly lower HOMA-IR.</p><p><strong>Conclusions: </strong>All <em>PPAR </em>SNPs were not associated with obesity and Met-S in the suburban population of Kampar, Malay­sia, where only <em>PPAR</em><em>α </em>V162 and <em>PPAR</em><em>γ</em><em>2 </em>T161 alleles were associated with plasma IL-6 and HOMA-IR, respectively. <em>Ethn Dis. </em>2015;25(4):383-390; doi:10.18865/ ed.25.4.383</p>

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