PMID- 24587943
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140303
LR  - 20211021
IS  - 2090-9446 (Print)
IS  - 2090-9446 (Electronic)
IS  - 2090-9446 (Linking)
VI  - 2014
DP  - 2014
TI  - Downregulation of RelA (p65) by Rapamycin Inhibits Murine Adipocyte 
      Differentiation and Reduces Fat Mass of C57BL/6J Mice despite High Fat Diet.
PG  - 540582
LID - 10.1155/2014/540582 [doi]
LID - 540582
AB  - 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-kappaB 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-kappaB 
      family.
FAU - Ray, Peter D
AU  - Ray PD
AD  - Department of Surgery, Division of Plastic Surgery, University of Alabama at 
      Birmingham, 1670 University Boulevard, VHG94, Birmingham, AL 35294, USA.
FAU - Maclellan, Reid A
AU  - Maclellan RA
AD  - Boston Children's Hospital, Department of Plastic and Oral Surgery, Boston, MA 
      02115, USA.
FAU - He, Jin
AU  - He J
AD  - Department of Surgery, Division of Plastic Surgery, University of Alabama at 
      Birmingham, 1670 University Boulevard, VHG94, Birmingham, AL 35294, USA.
FAU - Liu, Zhigang
AU  - Liu Z
AD  - Renmin Hospital of Wuhan University, Department of Anesthesiology, Wuhan, Hubei 
      430060, China.
FAU - Wu, Jianguo
AU  - Wu J
AD  - Department of Surgery, Division of Plastic Surgery, University of Alabama at 
      Birmingham, 1670 University Boulevard, VHG94, Birmingham, AL 35294, USA.
LA  - eng
PT  - Journal Article
DEP - 20140123
PL  - United States
TA  - ISRN Obes
JT  - ISRN obesity
JID - 101607056
PMC - PMC3920817
EDAT- 2014/03/04 06:00
MHDA- 2014/03/04 06:01
PMCR- 2014/01/23
CRDT- 2014/03/04 06:00
PHST- 2013/10/08 00:00 [received]
PHST- 2013/11/20 00:00 [accepted]
PHST- 2014/03/04 06:00 [entrez]
PHST- 2014/03/04 06:00 [pubmed]
PHST- 2014/03/04 06:01 [medline]
PHST- 2014/01/23 00:00 [pmc-release]
AID - 10.1155/2014/540582 [doi]
PST - epublish
SO  - ISRN Obes. 2014 Jan 23;2014:540582. doi: 10.1155/2014/540582. eCollection 2014.