Table of Contents
ISRN Obesity
Volume 2014, Article ID 540582, 7 pages
http://dx.doi.org/10.1155/2014/540582
Research Article

Downregulation of RelA (p65) by Rapamycin Inhibits Murine Adipocyte Differentiation and Reduces Fat Mass of C57BL/6J Mice despite High Fat Diet

1Department of Surgery, Division of Plastic Surgery, University of Alabama at Birmingham, 1670 University Boulevard, VHG94, Birmingham, AL 35294, USA
2Boston Children’s Hospital, Department of Plastic and Oral Surgery, Boston, MA 02115, USA
3Renmin Hospital of Wuhan University, Department of Anesthesiology, Wuhan, Hubei 430060, China

Received 8 October 2013; Accepted 20 November 2013; Published 23 January 2014

Academic Editors: B. Navia and C. H. Wu

Copyright © 2014 Peter D. Ray 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.

Abstract

Rapamycin (RAPA) is a clinical immunosuppressive agent first reported in the literature in 1975 after its discovery in a soil sample from the island of Rapa Nui. Aside from the well-documented effects of RAPA on cell division and immunologic response, the literature reveals it to have negative effects on adipocyte and osteocyte differentiation as well. Understanding of the molecular effects of RAPA on cell differentiation is fragmentary in regard to these cell lineages. In this paper, we examined a potential mechanism for RAPA’s effects on adipocyte differentiation in vitro and in vivo. The data point to a unique role of Rel A (p65)—a component of the NF-B system—in mediating this event. In murine adipose derived stem cell cultures (muADSCs) from C57BL/6J mice, RAPA was found to selectively downregulate RelA/p65, mammalian target of rapamycin (mTOR), and do so in a dose-dependent manner. This implies a novel role for RelA in adipocyte biology. Intracellular lipid accumulation—as subjectively observed—was also decreased in muADSCs treated with RAPA. Mice treated with RAPA had reduced overall body weight and reduced size of both intraabdominal and subcutaneous fat pads. When treated with RAPA, mice fed a high fat diet did not develop obesity and were not different from their regular diet controls in terms of body weight. These results suggested that RAPA inhibits adipogenesis and lipogenesis of muADSCs resulting in a prevention of obesity in C57BL/6J mice. This inhibition is strong enough to negate the effects of a high fat diet and seems to act by downregulating the RelA/p65 mTOR signaling pathway—a key component of the NF-B family.