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PPARγ is a ligand-activated transcription factor and member of the nuclear hormone receptor superfamily.1 It is composed of an N-terminal AF1 domain responsible for ligand-independent transactivation, a DNA-binding domain (DBD), a hinge region, and a C-terminal ligand-binding domain (LBD) and AF2 domain.2 It is expressed as two main isoforms, PPARγ1 and PPARγ2, and localizes to the nucleus. PPARγ1 is expressed in adipose tissue, liver, colon, heart, skeletal muscle, and various immune cells, and PPARγ2 is expressed primarily in adipose tissue but also in urothelial cells and certain populations of T cells.3 PPARγ has a large ligand-binding pocket that can be bound by a variety of ligands, including eicosanoids, thyroid and steroid hormones, and vitamins, as well as xenobiotics.1,2,3 When activated, PPARγ regulates gene expression to increase differentiation in white and brown adipose tissue and to reduce cytokine production in macrophages and chemokine production in T cells.3 It also regulates the expression of genes to increase lipid transport and metabolism in adipocytes and dendritic cells. PPARγ plays a role in diabetes and a more complex role in a variety of other diseases, including cancer, cardiovascular disease, and allergic disease.4,3,5,6 Formulations containing PPARγ agonists have been used in the treatment of type 2 diabetes.
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1. PPARγ: A nuclear regulator of metabolism differentiation, and cell growth. The Journal of Biological Chemisty 276(1), 37731-37734 (2001).
2. Peroxisome proliferator-
3. PPARgamma in metabolism, immunity, and cancer: Unified and diverse mechanisms of action. Front. Endocrinol. (Lausanne) 12, 624112 (2021).
4. PPARγ and diabetes: Beyond the genome and towards personalized medicine. Curr. Diab. Rep. 21(6), 18 (2021).
5. PPARγ and its role in cardiovascular diseases. PPAR Res. 6404638 (2017).
6. The role of PPAR-