Peroxisome proliferator-activated receptors

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Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (primarily lipid metabolism) and tumorigenesis of higher organisms.

Types and Functions[edit | edit source]

There are three types of PPARs in the nuclear hormone receptor family, each encoded by a different gene:

  • PPARα (NR1C1) - Found mainly in the liver, kidney, heart, and muscle, PPARα regulates lipid metabolism and is involved in the process of energy homeostasis. It is activated by fatty acids and fibrate drugs.
  • PPARδ (also known as PPARβ or NR1C2) - Expressed in many tissues but markedly in the brain, adipose tissue, and skin. PPARδ is involved in the regulation of fatty acid burning and storage, energy expenditure, and wound healing.
  • PPARγ (NR1C3) - Predominantly expressed in adipose tissue, PPARγ is crucial for adipocyte differentiation and glucose metabolism and is a primary target of anti-diabetic drugs like thiazolidinediones.

Mechanism of Action[edit | edit source]

PPARs function as regulators of lipid and glucose metabolism. They are activated by ligands such as fatty acids and eicosanoids. Upon activation, PPARs form heterodimers with the retinoid X receptor (RXR), and this complex binds to specific regions on DNA called PPAR response elements (PPREs). Binding to PPREs influences the transcription of various genes, particularly those involved in energy balance and lipid metabolism.

Clinical Significance[edit | edit source]

PPARs are targets for drugs used in the treatment of hyperlipidemia and diabetes mellitus type 2. For example, fibrates that activate PPARα are used to lower triglycerides, while thiazolidinediones that activate PPARγ are used to increase insulin sensitivity.

Research[edit | edit source]

Research on PPARs continues to reveal their potential in treating metabolic syndrome, obesity, and cardiovascular diseases. Studies are also exploring the role of PPARs in inflammation and cancer, providing a broader understanding of these receptors in disease modulation.

See Also[edit | edit source]


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Contributors: Prab R. Tumpati, MD