scholarly journals Pioglitazone versus Rosiglitazone: Effects on Lipids, Lipoproteins, and Apolipoproteins in Head-to-Head Randomized Clinical Studies

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Mark A. Deeg ◽  
Meng H. Tan
Keyword(s):  
Clinical Trials ◽  
Lipid Metabolism ◽  
Glucose Metabolism ◽  
Randomized Clinical Trials ◽  
Peroxisome Proliferator ◽  
Glucose Lowering ◽  
Glucose And Lipid Metabolism ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Regulate Lipid Metabolism

Peroxisome proliferator-activated receptors (PPARs) play an important role in regulating both glucose and lipid metabolism. Agonists for both PPAR and PPAR have been used to treat dyslipidemia and hyperglycemia, respectively. In addition to affecting glucose metabolism, PPAR agonists also regulate lipid metabolism. In this review, we will focus on the randomized clinical trials that directly compared the lipid effects of the thiazolidinedione class of PPAR agonists, pioglitazone and rosiglitazone, head-to-head either as monotherapy or in combination with other lipid-altering or glucose-lowering agents

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 (PPARS)

2020 ◽  
Vol 1 (3) ◽  
pp. 40-54
Author(s):  
Sumbal Sarwar ◽  
Shabana
Keyword(s):  
Fatty Acid ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Differential Distribution ◽  
Glucose And Lipid Metabolism ◽  
Cholesterol Levels ◽  
Ppar Agonists ◽  
Cardiac Muscles ◽  
Peroxisome Proliferator Activated Receptors ◽  
Realistic Data

Peroxisome proliferator-activated receptors are a group (PPARs) of transcription factors whose differential distribution in different tissues, including adipocytes, hepatocytes, musclesand endothelial cells lead to different clinical outcomes. They are called lipid and insulin sensors due to the important role in lipid and glucose homeostasis. They are mainly of threetypes; 1) PPAR? which influences fatty acid metabolism and its activation lowers lipid levels,2) PPAR? causes fatty acid oxidation in skeletal and cardiac muscles, as well as regulatesblood glucose and cholesterol levels and 3) PPAR? which is mostly involved in the regulationof the adipogenesis, energy balance, and lipid biosynthesis. The expression of these receptorsis influenced by many natural and synthetic ligands. Realistic data on the expression andfunction of natural PPAR agonists on glucose and lipid metabolism are still missing, mostlybecause the same ligand influences several receptors and a number of reports have providedconflicting results. The current minireview focuses on the structure, functions, types andligands of the PPAR.

scholarly journals Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1638 ◽  
Author(s):  
Anne Fougerat ◽  
Alexandra Montagner ◽  
Nicolas Loiseau ◽  
Hervé Guillou ◽  
Walter Wahli
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Peroxisome Proliferator ◽  
Biological Processes ◽  
Alcoholic Fatty Liver ◽  
Glucose And Lipid Metabolism ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis is the initial stage of the disease, which is characterized by lipid accumulation in hepatocytes, which can progress to non-alcoholic steatohepatitis (NASH) with inflammation and various levels of fibrosis that further increase the risk of developing cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is influenced by interactions between genetic and environmental factors and involves several biological processes in multiple organs. No effective therapy is currently available for the treatment of NAFLD. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate many functions that are disturbed in NAFLD, including glucose and lipid metabolism, as well as inflammation. Thus, they represent relevant clinical targets for NAFLD. In this review, we describe the determinants and mechanisms underlying the pathogenesis of NAFLD, its progression and complications, as well as the current therapeutic strategies that are employed. We also focus on the complementary and distinct roles of PPAR isotypes in many biological processes and on the effects of first-generation PPAR agonists. Finally, we review novel and safe PPAR agonists with improved efficacy and their potential use in the treatment of NAFLD.

scholarly journals PPARs and the Development of Type 1 Diabetes

PPAR Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Laurits J. Holm ◽  
Mia Øgaard Mønsted ◽  
Martin Haupt-Jorgensen ◽  
Karsten Buschard
Keyword(s):  
Type 1 Diabetes ◽  
Cell Biology ◽  
Pancreatic Beta Cells ◽  
Cell Types ◽  
Peroxisome Proliferator ◽  
Glucose And Lipid Metabolism ◽  
Novel Approach ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors with a key role in glucose and lipid metabolism. PPARs are expressed in many cell types including pancreatic beta cells and immune cells, where they regulate insulin secretion and T cell differentiation, respectively. Moreover, various PPAR agonists prevent diabetes in the non-obese diabetic (NOD) mouse model of type 1 diabetes. PPARs are thus of interest in type 1 diabetes (T1D) as they represent a novel approach targeting both the pancreas and the immune system. In this review, we examine the role of PPARs in immune responses and beta cell biology and their potential as targets for treatment of T1D.

New trends in the pharmacological intervention of PPARs in obesity: Role of natural and synthetic compounds_

2020 ◽  
Vol 28 ◽  
Author(s):  
Seyed Mohammad Nabavi ◽  
Kasi Pandima Devi ◽  
Sethuraman Sathya ◽  
Ana Sanches-Silva ◽  
Listos Joanna ◽  
...  
Keyword(s):  
Tissue Expression ◽  
Health Concern ◽  
Pharmacological Intervention ◽  
Peroxisome Proliferator ◽  
Expression Of Genes ◽  
Ppar Agonists ◽  
Prevalence Of Obesity ◽  
Peroxisome Proliferator Activated Receptors ◽  
Natural And Synthetic

: Obesity is a major health concern for a growing fraction of the population, with the prevalence of obesity and its related metabolic disorders not being fully understood. Over the last decade, many attempts have been undertaken to understand the mechanisms at the basis of this condition, in which the accumulation of fat occurring in adipose tissue, leads to the pathogenesis of obesity related disorders. Among the most recent studies, those on Peroxisome Proliferator Activated Receptors (PPARs) revealed that these nuclear receptor proteins acting as transcription factors, among others, regulate the expression of genes involved in energy, lipid, and glucose metabolisms, and chronic inflammation. The three different isotypes of PPARs, with different tissue expression and ligand binding specificity, exert similar or overlapping functions directly or indirectly linked to obesity. In this study, we reviewed the available scientific reports concerning the PPARs structure and functions, especially in obesity, considering both natural and synthetic ligands and their role in the therapy of obesity and obesity-associated disorders. In the whole, the collected data show that there are both natural and synthetic compounds that show beneficial promising activity as PPAR agonists in chronic diseases related to obesity.

Peroxisome Proliferator-Activated Receptors and Lipid Metabolism

1993 ◽  
Vol 684 (1 Zinc-Finger P) ◽  
pp. 157-173 ◽  
Author(s):  
HANSJÖRG KELLER ◽  
ABDERRAHIM MAHFOUDI ◽  
CHRISTINE DREYER ◽  
ABDELMADJID K. HIHI ◽  
JEFFREY MEDIN ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals PPAR-δin Vascular Pathophysiology

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
Nanping Wang
Keyword(s):  
Transcription Factors ◽  
Cell Growth ◽  
Glucose Metabolism ◽  
Nuclear Receptor ◽  
Therapeutic Intervention ◽  
Peroxisome Proliferator ◽  
Cardiovascular Disorders ◽  
Direct Effects ◽  
Cell Growth And Differentiation ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors belong to the superfamily of ligand-dependent nuclear receptor transcription factors, which include three subtypes: PPAR-α,β/δ, andγ. PPAR-δ, play important roles in the regulation of cell growth and differentiation as well as tissue wound and repair. Emerging evidence has also demonstrated that PPAR-δis implicated in lipids and glucose metabolism. Most recently, the direct effects of PPAR-δon cardiovascular processes such as endothelial function and angiogenesis have also been investigated. Therefore, it is suggested that PPAR-δmay have critical roles in cardiovascular pathophysiology and is a potential target for therapeutic intervention of cardiovascular disorders such as atherosclerosis.

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