PMID- 18483477
OWN - NLM
STAT- MEDLINE
DCOM- 20080912
LR  - 20101118
IS  - 1930-7381 (Print)
IS  - 1930-7381 (Linking)
VI  - 16
IP  - 7
DP  - 2008 Jul
TI  - Amyloid precursor protein expression is upregulated in adipocytes in obesity.
PG  - 1493-500
LID - 10.1038/oby.2008.267 [doi]
AB  - The aim of this study was to determine whether amyloid precursor protein (APP) is 
      expressed in human adipose tissue, dysregulated in obesity, and related to 
      insulin resistance and inflammation. APP expression was examined by microarray 
      expression profiling of subcutaneous abdominal adipocytes (SAC) and cultured 
      preadipocytes from obese and nonobese subjects. Quantitative real-time PCR (QPCR) 
      was performed to confirm differences in APP expression in SAC and to compare APP 
      expression levels in adipose tissue, adipocytes, and stromal vascular cells 
      (SVCs) from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) 
      specimens. Adipose tissue samples were also examined by western blot and 
      immunofluorescence confocal microscopy. Microarray studies demonstrated that APP 
      mRNA expression levels were higher in SAC (approximately 2.5-fold) and 
      preadipocytes (approximately 1.4) from obese subjects. Real-time PCR confirmed 
      increased APP expression in SAC in a separate group of obese compared with 
      nonobese subjects (P=0.02). APP expression correlated to in vivo indices of 
      insulin resistance independently of BMI and with the expression of 
      proinflammatory genes, such as monocyte chemoattractant protein-1 (MCP-1) 
      (R=0.62, P=0.004), macrophage inflammatory protein-1alpha (MIP-1alpha) (R=0.60, 
      P=0.005), and interleukin-6 (IL-6) (R=0.71, P=0.0005). Full-length APP protein 
      was detected in adipocytes by western blotting and APP and its cleavage peptides, 
      Abeta40 and Abeta42, were observed in SAT and VAT by immunofluorescence confocal 
      microscopy. In summary, APP is highly expressed in adipose tissue, upregulated in 
      obesity, and expression levels correlate with insulin resistance and adipocyte 
      cytokine expression levels. These data suggest a possible role for APP and/or 
      Abeta in the development of obesity-related insulin resistance and adipose tissue 
      inflammation.
FAU - Lee, Yong-Ho
AU  - Lee YH
AD  - Diabetes and Metabolism Translational Medicine Unit, University of Vermont 
      College of Medicine, Burlington, Vermont, USA.
FAU - Tharp, William G
AU  - Tharp WG
FAU - Maple, Rhonda L
AU  - Maple RL
FAU - Nair, Saraswathy
AU  - Nair S
FAU - Permana, Paska A
AU  - Permana PA
FAU - Pratley, Richard E
AU  - Pratley RE
LA  - eng
GR  - M01 RR000109/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080515
PL  - United States
TA  - Obesity (Silver Spring)
JT  - Obesity (Silver Spring, Md.)
JID - 101264860
RN  - 0 (APP protein, human)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Peptide Fragments)
RN  - 0 (Protease Nexins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (amyloid beta-protein (1-40))
RN  - 0 (amyloid beta-protein (1-42))
SB  - IM
MH  - Adipocytes/*metabolism
MH  - Adult
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/genetics/*metabolism
MH  - Blotting, Western
MH  - Body Mass Index
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Female
MH  - Gene Expression Profiling
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - *Insulin Resistance
MH  - Intra-Abdominal Fat/blood supply/*metabolism/physiopathology
MH  - Male
MH  - Microscopy, Confocal
MH  - Obesity/genetics/*metabolism/physiopathology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Panniculitis/genetics/*metabolism/physiopathology
MH  - Peptide Fragments/metabolism
MH  - Polymerase Chain Reaction
MH  - Protease Nexins
MH  - RNA, Messenger/metabolism
MH  - Receptors, Cell Surface/genetics/*metabolism
MH  - Stromal Cells/metabolism
MH  - Subcutaneous Fat, Abdominal/blood supply/*metabolism/physiopathology
MH  - Up-Regulation
EDAT- 2008/05/17 09:00
MHDA- 2008/09/16 09:00
CRDT- 2008/05/17 09:00
PHST- 2008/05/17 09:00 [pubmed]
PHST- 2008/09/16 09:00 [medline]
PHST- 2008/05/17 09:00 [entrez]
AID - oby2008267 [pii]
AID - 10.1038/oby.2008.267 [doi]
PST - ppublish
SO  - Obesity (Silver Spring). 2008 Jul;16(7):1493-500. doi: 10.1038/oby.2008.267. Epub 
      2008 May 15.