PMID- 9832419
OWN - NLM
STAT- MEDLINE
DCOM- 19981224
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 139
IP  - 12
DP  - 1998 Dec
TI  - Functional analysis of tumor necrosis factor (TNF) receptors in 
      TNF-alpha-mediated insulin resistance in genetic obesity.
PG  - 4832-8
AB  - Although obesity has become the most common metabolic disorder in the developed 
      world and is highly associated with insulin resistance and noninsulin-dependent 
      diabetes mellitus, the molecular mechanisms underlying these disorders are not 
      clearly understood. Tumor necrosis factor-alpha (TNF-alpha) is overexpressed in 
      obesity and is a candidate mediator of obesity-induced insulin resistance. 
      Complete lack of TNF-alpha function through targeted mutations in TNF-alpha gene 
      or both of its receptors results in significant improvement of insulin 
      sensitivity in dietary, chemical, or genetic models of rodent obesity. In this 
      study, we have analyzed the in vivo role of TNF signaling from p55 [TNF receptor 
      (TNFR) 1] and p75 (TNFR 2) TNFR in the development of insulin resistance by 
      generating genetically obese mice (ob/ob) lacking p55 or p75 TNFRs. In the ob/ob 
      mice, the absence of p55 caused a significant improvement in insulin sensitivity. 
      p75 deficiency alone did not affect insulin sensitivity but might potentiate the 
      effects of p55 deficiency in animals lacking both TNFRs. These results indicate 
      that TNF-alpha is a component of insulin resistance in the ob/ob model of murine 
      obesity and p55 TNFR is the predominant receptor mediating its actions.
FAU - Uysal, K T
AU  - Uysal KT
AD  - Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 
      02115, USA.
FAU - Wiesbrock, S M
AU  - Wiesbrock SM
FAU - Hotamisligil, G S
AU  - Hotamisligil GS
LA  - eng
GR  - DK-52539/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  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Lipids)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Body Composition/physiology
MH  - Glucose/metabolism
MH  - Glucose Tolerance Test
MH  - Homeostasis/physiology
MH  - Insulin Resistance/*physiology
MH  - Lipids/blood
MH  - Mice/genetics/growth & development
MH  - Mutation/physiology
MH  - Obesity/*genetics/metabolism/pathology
MH  - Receptors, Tumor Necrosis Factor/deficiency/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/*physiology
EDAT- 1998/12/01 00:00
MHDA- 1998/12/01 00:01
CRDT- 1998/12/01 00:00
PHST- 1998/12/01 00:00 [pubmed]
PHST- 1998/12/01 00:01 [medline]
PHST- 1998/12/01 00:00 [entrez]
AID - 10.1210/endo.139.12.6337 [doi]
PST - ppublish
SO  - Endocrinology. 1998 Dec;139(12):4832-8. doi: 10.1210/endo.139.12.6337.