Table of Contents
ISRN Obesity
Volume 2013 (2013), Article ID 161345, 9 pages
Research Article

Dysregulated Alternative Splicing Pattern of PKC during Differentiation of Human Preadipocytes Represents Distinct Differences between Lean and Obese Adipocytes

1James A. Haley Veterans' Hospital, Research Service VAR 151, 13000 Bruce B. Downs Boulevard, Tampa, FL 33612, USA
2Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
3Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA

Received 15 January 2013; Accepted 5 March 2013

Academic Editors: H. Gordish-Dressman, U. J. Magalang, and S. Straube

Copyright © 2013 Gay Carter et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Obesity and its comorbidities affect millions of people. Here, we demonstrate that human preadipocytes are susceptible to programmed cell death (apoptosis) while mature adipocytes are resistant to apoptosis. The molecular mechanisms underlying the phenotype of apoptosis-resistant adipocytes are lesser known. To study the role of apoptosis and define molecular differences in the developmental process of adipogenesis, human preadipocytes were differentiated in vitro to mature adipocytes. Many genes in the apoptosis pathway are alternatively spliced. Our data demonstrates that during differentiation PKCδ, Bclx, and Caspase9 switch to their prosurvival splice variants along with an increase in Bcl2 expression when the cells terminally differentiate into mature adipocytes. Next we determined the expression pattern of these genes in obesity. Our data indicated high expression of PKCδVIII in adipose tissue of obese patient in different depots. We demonstrate a shift in the in vitro expression of these splice variants in differentiating preadipocytes derived from obese patients along with a decrease in adipogenesis markers. Hence, the programmed splicing of antiapoptotic proteins is a pivotal switch in differentiation that commits adipocytes to a prosurvival pathway. The expression pattern of these genes is dysregulated in obesity and may contribute to adipose tissue dysfunction.