Research Article Downregulation of RelA (p65) by Rapamycin Inhibits Murine Adipocyte Differentiation and Reduces Fat Mass of C57BL/6J Mice despite High Fat Diet Peter D. Ray, 1 Reid A. Maclellan, 2 Jin He, 1 Zhigang Liu, 3 and Jianguo Wu 1 1 Department of Surgery, Division of Plastic Surgery, University of Alabama at Birmingham, 1670 University Boulevard, VHG94, Birmingham, AL 35294, USA 2 Boston Children’s Hospital, Department of Plastic and Oral Surgery, Boston, MA 02115, USA 3 Renmin Hospital of Wuhan University, Department of Anesthesiology, Wuhan, Hubei 430060, China Correspondence should be addressed to Peter D. Ray; peter.ray@childrensal.org and Jianguo Wu; jgwu@uab.edu 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. his 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. Rapamycin (RAPA) is a clinical immunosuppressive agent irst reported in the literature in 1975 ater its discovery in a soil sample from the island of Rapa Nui. Aside from the well-documented efects of RAPA on cell division and immunologic response, the literature reveals it to have negative efects on adipocyte and osteocyte diferentiation as well. Understanding of the molecular efects of RAPA on cell diferentiation is fragmentary in regard to these cell lineages. In this paper, we examined a potential mechanism for RAPA’s efects on adipocyte diferentiation in vitro and in vivo. he 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. his 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 diferent from their regular diet controls in terms of body weight. hese results suggested that RAPA inhibits adipogenesis and lipogenesis of muADSCs resulting in a prevention of obesity in C57BL/6J mice. his inhibition is strong enough to negate the efects 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. 1. Introduction In the 1950s molecular geneticists were trying to determine if proteins built from amino acids were required for the synthesis of nucleic acid chains or vice versa [1]. As a result of this work, the Rel gene was described in E. coli in 1969 [2] and so named because when the gene was present it rendered “relaxed” mutants of E. coli more stringently dependent on the presence of speciic amino acids for successful RNA synthesis. “Rel proteins” share genetic homology and yet initiate diferent proliferative and/or transformative efects on diferent cells [3]. he irst described “Rel protein” (REV-T) was most intriguing because of its ability to transform cells into malignant populations [4]. A viral form (v-Rel) was then also identiied in birds, implying that there existed a related homology across species of these regulator proteins [5]. Due to their ability to drive replication and transformation from bacteria to mammals, the Rel genes were studied extensively in an attempt to understand their relation to malignancy [6, 7]. Further investigation to identify proteins related to c-Rel identiied a number of subunits which were found to exist bound to each other as dimers or heterodimers. his led to the concept of a “Rel family of proteins,” meaning a set of proteins that regulate transcription and possess the structural ability to form complexes required for DNA binding. Rel family Hindawi Publishing Corporation ISRN Obesity Volume 2014, Article ID 540582, 7 pages http://dx.doi.org/10.1155/2014/540582