PMID- 21998397
OWN - NLM
STAT- MEDLINE
DCOM- 20120201
LR  - 20211020
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 60
IP  - 12
DP  - 2011 Dec
TI  - Deficiency for costimulatory receptor 4-1BB protects against obesity-induced 
      inflammation and metabolic disorders.
PG  - 3159-68
LID - 10.2337/db10-1805 [doi]
AB  - OBJECTIVE: Inflammation is an important factor in the development of insulin 
      resistance, type 2 diabetes, and fatty liver disease. As a member of the tumor 
      necrosis factor receptor superfamily (TNFRSF9) expressed on immune cells, 
      4-1BB/CD137 provides a bidirectional inflammatory signal through binding to its 
      ligand 4-1BBL. Both 4-1BB and 4-1BBL have been shown to play an important role in 
      the pathogenesis of various inflammatory diseases. RESEARCH DESIGN AND METHODS: 
      Eight-week-old male 4-1BB-deficient and wild-type (WT) mice were fed a high-fat 
      diet (HFD) or a regular diet for 9 weeks. RESULTS: We demonstrate that 4-1BB 
      deficiency protects against HFD-induced obesity, glucose intolerance, and fatty 
      liver disease. The 4-1BB-deficient mice fed an HFD showed less body weight gain, 
      adiposity, adipose infiltration of macrophages/T cells, and tissue levels of 
      inflammatory cytokines (e.g., TNF-alpha, interleukin-6, and monocyte chemoattractant 
      protein-1 [MCP-1]) compared with HFD-fed control mice. HFD-induced glucose 
      intolerance/insulin resistance and fatty liver were also markedly attenuated in 
      the 4-1BB-deficient mice. CONCLUSIONS: These findings suggest that 4-1BB and 
      4-1BBL may be useful therapeutic targets for combating obesity-induced 
      inflammation and metabolic disorders.
FAU - Kim, Chu-Sook
AU  - Kim CS
AD  - Department of Food Science and Nutrition, University of Ulsan, Ulsan, South 
      Korea.
FAU - Kim, Jae Geun
AU  - Kim JG
FAU - Lee, Byung-Ju
AU  - Lee BJ
FAU - Choi, Myung-Sook
AU  - Choi MS
FAU - Choi, Hye-Sun
AU  - Choi HS
FAU - Kawada, Teruo
AU  - Kawada T
FAU - Lee, Ki-Up
AU  - Lee KU
FAU - Yu, Rina
AU  - Yu R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111013
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (4-1BB Ligand)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor Receptor Superfamily, Member 9)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
CIN - Diabetes. 2012 Jul;61(7):e6; author reply e7. PMID: 22723280
MH  - 4-1BB Ligand/metabolism
MH  - Adipose Tissue/drug effects/metabolism
MH  - Adiposity/genetics/physiology
MH  - Animals
MH  - Blotting, Western
MH  - Body Weight/genetics/physiology
MH  - Calorimetry, Indirect
MH  - Chemokine CCL2/metabolism
MH  - Diet, High-Fat/*adverse effects
MH  - Flow Cytometry
MH  - Glucose Intolerance
MH  - Inflammation/genetics/*metabolism
MH  - Interleukin-6/metabolism
MH  - Liver/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Obesity/*physiopathology
MH  - Real-Time Polymerase Chain Reaction
MH  - Tumor Necrosis Factor Receptor Superfamily, Member 9/*deficiency/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC3219944
EDAT- 2011/10/15 06:00
MHDA- 2012/02/02 06:00
PMCR- 2012/12/01
CRDT- 2011/10/15 06:00
PHST- 2011/10/15 06:00 [entrez]
PHST- 2011/10/15 06:00 [pubmed]
PHST- 2012/02/02 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - db10-1805 [pii]
AID - 1805 [pii]
AID - 10.2337/db10-1805 [doi]
PST - ppublish
SO  - Diabetes. 2011 Dec;60(12):3159-68. doi: 10.2337/db10-1805. Epub 2011 Oct 13.