Molecular docking of Glyceroneogenesis pathway intermediates with Peroxisome Proliferator- Activated Receptor-Alpha (PPAR-α)
نویسندگان
چکیده
Peroxisome proliferator-activated receptor alpha (PPAR-α) belongs to the nuclear receptor superfamily of proteins. It is one of the principle regulators of metabolism and lipid homeostasis whose malfunction leads to complications including obesity and type 2 diabetes. In the adipose tissue, glyceroneogenesis is a unique pathway through which pyruvate is converted into glycerol-3- phosphate (G3P) in a multistep process. Previous findings demonstrated that glyceroneogenesis regulates triacylglycerol synthesis and adipogenesis. This led us to hypothesize that one of the pathway intermediate is physiologically relevant PPAR-α ligand. In the present study using in silico docking, we proved that glycerate, dihydroxy acetone phosphate, glyceraldehyde-3-phosphate, and G3P are key glyceroneogenesis pathway intermediates which bind to PPAR-α. They bind PPAR-α with comparable binding energy and docking score to that of (2s)-2-ethoxy-3-[4-(2-{4-[(methylsulfonyl)oxy]phenyl}ethoxy)phenyl]propanoic acid(AZ-2), a synthetic high affinity ligand of PPAR-α. These intermediates could be studied further as potential physiologically relevant activators of PPAR-α in vitro and in vivo.
منابع مشابه
The Role of Peroxisome Proliferator Activator Receptor Alpha in Cerebral Ischemia-Reperfusion Injury; a Review Study
Peroxisome proliferator-activated receptor alpha (PPAR-α), which belongs to the nuclear receptor family of ligand-activated transcription factors, was first described as gene regulators for metabolic pathways including lipid metabolism, insulin sensitivity, and glucose homeostasis. Were raised. This nuclear receptor is widely expressed in various tissues, providing a wide range of effects to st...
متن کاملCompare the Effect of Eicosapentaenoic Acid and Oxidized Low-Density Lipoprotein on the Expression of CD36 and Peroxisome Proliferator-Activated Receptor Gamma
Background: There is evidence that CD36 promotes foam cell formation through internalizing oxidized LDL (ox-LDL) into macrophages therefore, it plays a key role in pathogenesis of atherosclerosis. In addition, CD36 expression seems to be mediated by nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ). The aim of the present study was to evaluate and compare the effect of ...
متن کاملRole of peroxisome proliferator-activated receptor alpha and gamma in antiangiogenic effect of pomegranate peel extract
Objective(s): Herbal medicines are promising cancer preventive candidates. It has been shown that Punica granatum L. could inhibit angiogenesis and tumor invasion. In this study, we investigated whether the anti-angiogenic effect of pomegranate peel extract (PPE) is partly attributable to Peroxisome proliferator-activated receptors (PPARs) activation in the Human Umbilical Vein Endothelial Cell...
متن کاملConjugated linoleic acid supplementation enhances insulin sensitivity and peroxisome proliferator-activated receptor gamma and glucose transporter type 4 protein expression in the skeletal muscles of rats during endurance exercise
Objective(s):This study examined whether conjugated linoleic acid (CLA) supplementation affects insulin sensitivity and peroxisome proliferator-activated receptor gamma (PPAR-γ) and glucose transporter type 4 (GLUT-4) protein expressions in the skeletal muscles of rats during endurance exercise. Materials and Methods:Sprague-Dawley male rats were randomly divided into HS (high-fat diet (HFD) s...
متن کاملاثرایمونوتراپیوتیک آل- ترانس رتینوئیک اسید بر دیابت تیپ 1 در موش و تاثیر آن بر بیان ژن (peroxisome proliferator- activated receptor gamma (PPARγ
Background: All-trans retinoic acid (ATRA) has a variety of biological activities, including immunomodulatory action in a number of inflammatory and autoimmune diseases. The purpose of this study was to investigate the effects of all-trans retinoic acid on the treatment of autoimmune diabetes in mice and its effects on expressions of Peroxisome Proliferator-Activated Receptor gamma (PPARγ...
متن کامل