The Peroxisome Proliferator-activated Receptor γ Regulates Expression of the Perilipin Gene in Adipocytes

Abstract

Reporter assays using the ؊2.0-kb promoter revealed that this region contains a functional PPAR␥-responsive element. Gel mobility shift and chromatin immunoprecipitation assays showed that endogenous PPAR␥ protein binds to the perilipin promoter. PPAR␥2, an isoform exclusively expressed in adipocytes, was found to be the most potent regulator from among the PPAR family members including PPAR␣ and PPAR␥1. These results make evident the fact that perilipin gene expression in differentiating adipocytes is crucially regulated by PPAR␥2, providing new insights into the adipogenic action of PPAR␥2 and adipose-specific gene expression, as well as potential anti-obesity pharmaceutical agents targeted to a reduction of the perilipin gene product.Adipocytes are the major reservoir of energy stored in the form of triacylglycerol in the body. Triacylglycerol is stored within intracellular lipid droplets covered by a monolayer of phospholipids, free cholesterol, and proteins. In times of energy need, for example, as brought about by activities such as fasting and/or exercise, catecholamines rapidly activate cAMP-dependent protein kinase (PKA), 1 resulting in hydrolysis of triacylglycerol as catalyzed by activated hormone-sensitive lipase.

CGI-58 Interacts with Perilipin and Is Localized to Lipid Droplets

“…Many adipocyte-specific genes, including the perilipin gene (38,39,46,47), are regulated by PPAR␥, a master regulator of adipogenesis (37). Accordingly, we were interested in whether the CGI-58 gene is also regulated by PPAR␥.…”

Genes of Cholesterol Metabolism in Human Atheroma

“…This action of fatty acids could be mediated through the nuclear receptors PPAR␥ because it has been shown that the promoter of the perilipin gene contains functional PPAR-responsive elements and that PPAR␥ agonists stimulate in adipocytes the expression of perilipin. 28,29 Perilipin opposes in adipocytes in the basal state the hydrolysis of TGs by HSL. 19 On stimulation of lipolysis by ␤-adrenergic agonists, perilipin is phosphorylated by the protein kinase PKA and allows phosphorylated HSL to access lipid droplets and hydrolyze TGs.…”

The 11482G>A Polymorphism in the Perilipin Gene Is Associated With Weight Gain With Rosiglitazone Treatment in Type 2 Diabetes

“…When fed a high fat diet, perilipin null mice are resistant to dietinduced obesity. PPAR␥ agonists are reported to stimulate perilipin gene expression in adipocytes (39). Reporter assays reveal that the 5Ј-flanking region of the gene contains a functional PPAR␥-responsive element (40).…”