PMID- 12031976
OWN - NLM
STAT- MEDLINE
DCOM- 20020624
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 51
IP  - 6
DP  - 2002 Jun
TI  - Altered tumor necrosis factor-alpha (TNF-alpha) processing in adipocytes and 
      increased expression of transmembrane TNF-alpha in obesity.
PG  - 1876-83
AB  - Tumor necrosis factor-alpha (TNF-alpha) is synthesized as a 26-kDa transmembrane 
      protein (mTNF-alpha), which may present on the cell surface or be processed to 
      release the 17-kDa soluble form (sTNF-alpha). Because regulation of this 
      ectodomain shedding might be critical in the generation of systemic versus local 
      cytokine responses, we examined the rate of mTNF-alpha processing in adipocytes 
      and its regulation in obesity. Here, we demonstrate that the 26-kDa mTNF-alpha is 
      present in adipose tissue and that its production is significantly increased in 
      different rodent obesity models as well as in obese humans. There was no apparent 
      deficiency in the level of the major TNF-alpha converting enzyme in adipose 
      tissue to account for the excess amount of mTNF-alpha produced in obesity. 
      However, experiments in cultured fat cells stably expressing TNF-alpha 
      demonstrated a significantly decreased rate of TNF-alpha cleavage in 
      differentiated adipocytes compared with preadipocytes. Thus, a decreased 
      processing rate of mTNF-alpha in mature adipocytes combined with an increase in 
      TNF-alpha production may be a potential mechanism resulting in elevated 
      membrane-associated TNF-alpha in adipose tissue in obesity.
FAU - Xu, Haiyan
AU  - Xu H
AD  - Division of Biological Sciences, Department of Nutrition, Harvard School of 
      Public Health, Boston, Massachusetts 02115, USA.
FAU - Uysal, K Teoman
AU  - Uysal KT
FAU - Becherer, J David
AU  - Becherer JD
FAU - Arner, Peter
AU  - Arner P
FAU - Hotamisligil, Gokhan S
AU  - Hotamisligil GS
LA  - eng
GR  - DK52539/DK/NIDDK NIH HHS/United States
GR  - DK54017/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Antigens, CD)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.86 (ADAM17 Protein)
SB  - IM
MH  - 3T3 Cells
MH  - ADAM Proteins
MH  - ADAM17 Protein
MH  - Adipocytes/*metabolism
MH  - Adipose Tissue/metabolism/ultrastructure
MH  - Adult
MH  - Animals
MH  - Antigens, CD/physiology
MH  - Cell Membrane/metabolism
MH  - Cells, Cultured
MH  - *Gene Expression
MH  - Humans
MH  - Immunosorbent Techniques
MH  - Metalloendopeptidases/genetics/metabolism
MH  - Mice
MH  - Middle Aged
MH  - Obesity/*metabolism
MH  - RNA, Messenger/analysis
MH  - Receptors, Tumor Necrosis Factor/deficiency/physiology
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Receptors, Tumor Necrosis Factor, Type II
MH  - Tumor Necrosis Factor-alpha/*genetics/*metabolism
EDAT- 2002/05/29 10:00
MHDA- 2002/06/25 10:01
CRDT- 2002/05/29 10:00
PHST- 2002/05/29 10:00 [pubmed]
PHST- 2002/06/25 10:01 [medline]
PHST- 2002/05/29 10:00 [entrez]
AID - 10.2337/diabetes.51.6.1876 [doi]
PST - ppublish
SO  - Diabetes. 2002 Jun;51(6):1876-83. doi: 10.2337/diabetes.51.6.1876.