P311, a novel intrinsically disordered protein, regulates adipocyte development

Adipocyte development and adipose tissue expansion have many implications for human diseases, including obesity. Obesity is a debilitating disorder and a risk factor for metabolic disorders including insulin resistance and diabetes mellitus, due in part to an overabundance of adipocytes and adipocyte dysfunction. In recent years, obesity has become a global pandemic with approximately one-third of US adults classified as obese. Adipose tissue has recently been identified as a major metabolic organ, classified into white adipose tissue (WAT) and brown adipose tissue (BAT). Other than lifestyle modifications and invasive surgeries, only a very limited number of drugs are available to treat obesity and overweight. P311 has been shown to play a key role in blood pressure regulation, vascular contractility and tissue remodeling. Here we present a role for P311 in adipogenesis using a 3T3-L1 cell culture model. P311 expression is initiated with the induction of adipogenesis and increased during adipogenesis. This increase correlates with an increase in the expression of the key adipogenic transcriptional factors PPAR gamma 2 and C/EBP alpha. In addition, siRNA-mediated P311 knockdown inhibits adipogenic differentiation in 3T3-L1 cells. Finally, P311 binds to the PPAR gamma 2 promoter, implicating P311 mediates adipogenesis partly through PPAR gamma activation. (C) 2019 Elsevier Inc. All rights reserved.