Peroxisome proliferator-activated receptor

Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors to regulate the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (primarily lipid metabolism and glucose homeostasis). There are three types of PPARs in mammals: PPAR-alpha (PPARα), PPAR-delta (PPARδ, also known as PPARβ), and PPAR-gamma (PPARγ). Each of these receptors has a distinct role in metabolic processes, which can vary by the tissue type in which they are expressed.

Function

PPARs are activated by ligands such as fatty acids and their derivatives. Upon activation, they form a heterodimer with the retinoid X receptor (RXR), and this complex then binds to specific response elements in the DNA to regulate gene expression. The functions of PPARs include:

• PPARα: Primarily found in liver, kidney, heart, and muscle tissues, PPARα regulates genes involved in fatty acid oxidation, which is critical for energy production during periods of fasting.
• PPARδ: Expressed in many tissues but most abundantly in the brain, adipose tissue, and skin. PPARδ regulates fatty acid storage and glucose metabolism, and it has been implicated in wound healing and other processes.
• PPARγ: Most abundantly expressed in adipose tissue, PPARγ regulates fatty acid storage and glucose metabolism. It is a major target for antidiabetic drugs, as it improves insulin sensitivity.

Clinical Significance

PPARs are targets for drugs used in the treatment of conditions such as diabetes, hyperlipidemia, and metabolic syndrome. For example, thiazolidinediones (TZDs) are PPARγ agonists used in the treatment of type 2 diabetes. Fibrates, which are PPARα agonists, are used to lower triglyceride levels in patients with hyperlipidemia.

Research Directions

Research into PPARs continues to uncover their potential therapeutic roles in various diseases, including obesity, diabetes, atherosclerosis, and even certain types of cancer. Understanding the complex roles of PPARs in metabolism and disease can lead to the development of new therapeutic strategies for metabolic disorders and beyond.

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