These observations raise the possibility that 1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid derivatives might be effective drug candidates for selective targeting of PPARα to manage dyslipidemia.
Fibrates, the ligands of peroxisome proliferator-activated receptor alpha (PPARalpha), are used as a class of lipid-lowering drugs in clinical practice for the treatment of dyslipidemia.
The selective peroxisome proliferator-activated receptor alpha modulator (SPPARM-α), pemafibrate, will be used to target residual cardiovascular risk remaining after treatment to reduce low-density lipoprotein cholesterol (LDL-C) in individuals with the dyslipidemia of type 2 diabetes mellitus (T2).
Fenofibrate, a third-generation fibric acid derivative, is an activator of PPARα indicated for the treatment of mixed dyslipidemia and hypertriglyceridemia in adults.
The present study was performed to evaluate the association between the PPARalpha polymorphism L162V and the presence of dyslipidemia and/or atherosclerotic disease in patients with DM-2 in comparison with nondiabetic controls.
To effectively target dyslipidemia to reduce the risk of cardiovascular disease, it may be beneficial to activate the peroxisome proliferator-activated receptors (PPARs) PPARalpha and PPARdelta simultaneously through a single molecule.
to assess the effect of functional single nucleotide polymorphisms (SNPs) of PPARα and PPARγ2, previously associated with insulin resistance and dyslipidemia, on liver damage in NAFLD, whose progression is influenced by metabolic abnormalities and inherited factors.
The compound 13m also increased the expression of genes involved in reverse cholesterol transport (RCT) such as PPARα and LXR1α indicating another mechanism by which compound 13m ameliorates dyslipidemia in Syrian Golden hamster model.
There is evidence that genetic variants within the PPARα gene have been associated with a risk of the development of dyslipidemia and cardiovascular disease by influencing fasting and postprandial lipid concentrations; the gene variants have also been associated with an acceleration of the progression of type 2 diabetes.
PPARalpha ligand fibrates have been used for the treatment of dyslipidemia due to their ability to lower plasma triglyceride levels and elevate HDL cholesterol levels.
This demonstrates that PPARalpha is a link between diabetes and dyslipidaemia, and so could influence the risk of coronary artery disease, the greatest cause of morbidity and mortality in Type II diabetes.
To our knowledge, this is the first study to report that 9-oxo-OTA promotes fatty acid metabolism via PPARα activation and discuss its potential as a valuable food-derived compound for use in the management of dyslipidemia.
Synthetic PPAR ligands are widely used in the treatment of dyslipidemia (e.g. fibrates - PPARα activators) or in diabetes mellitus (e.g. thiazolidinediones - PPARγ agonists) while a new generation of dual agonists reveals hypolipemic, hypotensive, antiatherogenic, anti-inflammatory and anticoagulant action.
Peroxisome proliferator activated receptor α (PPARα), a drug target for dyslipidemia, is known to be downregulated in cardiomyocytes in response to hypertrophic stimuli.
Fenofibrate is a peroxisome proliferator-activated receptor-alpha (PPARalpha) activator that has been clinically used to treat dyslipidemia and insulin resistance.
Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, has been used for decades to treat hypertriglyceridaemia and mixed dyslipidaemia.
Furthermore, MG clearly alleviated serum TG and total cholesterol release; upregulated AKT, AMPK, and PPARα expression; suppressed SREBP-1c generation; and alleviated hepatic steatosis and dyslipidemia in Ty-induced hyperlipidemia mice.
Single gene contributions: genetic variants of peroxisome proliferator-activated receptor (isoforms alpha, beta/delta and gamma) and mechanisms of dyslipidemias.
The common Leu162Val polymorphism in the gene encoding PPARalpha has inconsistently shown association with quantitative traits related to obesity, type 2 diabetes, and dyslipidaemia.
Select compounds were evaluated in animal models of dyslipidemia using Syrian hamsters and male Beagle dogs, and all these compounds displayed excellent cholesterol- and triglyceride-lowering activity at dose levels that were much lower than the marketed weak PPARalpha agonist fenofibrate.
Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia.
Discovery of a novel series of peroxisome proliferator-activated receptor alpha/gamma dual agonists for the treatment of type 2 diabetes and dyslipidemia.