Journal Article

Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications – a review

Grygiel-Górniak, Bogna

2014

Overview

Peroxisome proliferator-activated receptors are expressed in many tissues, including adipocytes, hepatocytes, muscles and endothelial cells; however, the affinity depends on the isoform of PPAR, and different distribution and expression profiles, which ultimately lead to different clinical outcomes. Because they play an important role in lipid and glucose homeostasis, they are called lipid and insulin sensors. Their actions are limited to specific tissue types and thus, reveal a characteristic influence on target cells. PPARα mainly influences fatty acid metabolism and its activation lowers lipid levels, while PPARγ is mostly involved in the regulation of the adipogenesis, energy balance, and lipid biosynthesis. PPARβ/δ participates in fatty acid oxidation, mostly in skeletal and cardiac muscles, but it also regulates blood glucose and cholesterol levels. Many natural and synthetic ligands influence the expression of these receptors. Synthetic ligands are widely used in the treatment of dyslipidemia (e.g. fibrates - PPARα activators) or in diabetes mellitus (e.g. thiazolidinediones - PPARγ agonists). New generation drugs - PPARα/γ dual agonists - reveal hypolipemic, hypotensive, antiatherogenic, anti-inflammatory and anticoagulant action while the overexpression of PPARβ/δ prevents the development of obesity and reduces lipid accumulation in cardiac cells, even during a high-fat diet. Precise data on the expression and function of natural PPAR agonists on glucose and lipid metabolism are still missing, mostly because the same ligand influences several receptors and a number of reports have provided conflicting results. To date, we know that PPARs have the capability to accommodate and bind a variety of natural and synthetic lipophilic acids, such as essential fatty acids, eicosanoids, phytanic acid and palmitoylethanolamide. A current understanding of the effects of PPARs, their molecular mechanisms and the role of these receptors in nutrition and therapeutic treatment are delineated in this paper.

• Publisher: Springer-Verlag,BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: adipocytes / agonists / Amino acids / Animals / anticoagulants / Biosynthesis / blood glucose / Blood pressure / Cholesterol / Clinical Nutrition / Diabetes / diabetes mellitus / diet therapy / drug effects / eicosanoids / endothelial cells / Energy balance / essential fatty acids / fatty acid metabolism / Fatty acids / Gene expression / Genetic aspects / glucose / Health Promotion and Disease Prevention / hepatocytes / high fat diet / Homeostasis / Humans / hyperlipidemia / insulin / Ligands / Lipids / lipogenesis / Medicine / Medicine & Public Health / Metabolic disorders / Metabolism / Muscles / Musculoskeletal system / obesity / oxidation / Peroxisome Proliferator-Activated Receptors / Peroxisome Proliferator-Activated Receptors - agonists / Peroxisome Proliferator-Activated Receptors - drug effects / Peroxisome Proliferator-Activated Receptors - physiology / Physiological aspects / physiology / PPAR alpha / PPAR alpha - physiology / PPAR delta / PPAR delta - physiology / PPAR gamma / PPAR gamma - physiology / PPAR-beta / PPAR-beta - physiology / receptors / Retinoid X Receptors / Retinoid X Receptors - physiology / Review / thiazolidinediones / Transcription, Genetic / Transcription, Genetic - physiology