Peroxisome proliferator-activated receptor alpha
(Redirected from HPPAR)
Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that plays an essential role in the regulation of cellular metabolism. Primarily expressed in tissues that exhibit high catabolic rates of fatty acids, such as the liver, kidney, heart, and muscle, PPARα activates genes involved in the fatty acid oxidation, lipid metabolism, and energy homeostasis. Activation of PPARα promotes the uptake, utilization, and catabolism of fatty acids by upregulating genes involved in fatty acid transport, fatty acid binding, and peroxisomal and mitochondrial fatty acid β-oxidation.
Function[edit | edit source]
PPARα is a key regulator of lipid metabolism. It is activated by natural ligands such as fatty acids and eicosanoids, as well as by synthetic drugs like fibrates, which are used clinically to treat dyslipidemia. Upon activation, PPARα forms a heterodimer with the retinoid X receptor (RXR) and binds to specific response elements in the DNA, leading to the transcription of genes involved in lipid metabolism processes. This includes the regulation of genes involved in the transport and oxidation of fatty acids, as well as those involved in lipoprotein assembly and cholesterol metabolism.
Clinical Significance[edit | edit source]
The role of PPARα in lipid metabolism makes it a target for therapeutic intervention in metabolic diseases. Fibrates, which are PPARα agonists, are used to lower plasma triglycerides and increase high-density lipoprotein (HDL) cholesterol levels in patients with dyslipidemia. Moreover, PPARα is implicated in the pathogenesis of several metabolic disorders, including obesity, diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Research is ongoing to develop new PPARα agonists with improved efficacy and safety profiles for the treatment of metabolic diseases.
Pharmacology[edit | edit source]
PPARα agonists, primarily fibrates, are used to modulate lipid levels in the blood. These drugs work by activating PPARα, leading to increased expression of genes involved in fatty acid oxidation and decreased expression of genes involved in lipogenesis. This results in reduced triglyceride levels and increased HDL cholesterol levels. The use of PPARα agonists is particularly beneficial in patients with hypertriglyceridemia and low HDL cholesterol levels.
Genetics[edit | edit source]
The gene encoding PPARα is located on chromosome 22. Variations in this gene can affect the expression and function of PPARα, potentially influencing an individual's risk of developing metabolic diseases. Genetic polymorphisms in the PPARα gene have been associated with differences in lipid metabolism and responses to fibrates.
Research Directions[edit | edit source]
Current research on PPARα is focused on understanding its role in metabolic diseases and developing new therapeutic agents that target this receptor. Studies are exploring the effects of PPARα activation on various aspects of metabolism, including glucose homeostasis, inflammation, and energy expenditure. Additionally, research is aimed at identifying novel natural and synthetic ligands for PPARα that could serve as potential treatments for metabolic disorders.
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Contributors: Prab R. Tumpati, MD