PMID- 19883619
OWN - NLM
STAT- MEDLINE
DCOM- 20100615
LR  - 20211020
IS  - 1932-7420 (Electronic)
IS  - 1550-4131 (Print)
IS  - 1550-4131 (Linking)
VI  - 10
IP  - 5
DP  - 2009 Nov
TI  - Hematopoietic cell-specific deletion of toll-like receptor 4 ameliorates hepatic 
      and adipose tissue insulin resistance in high-fat-fed mice.
PG  - 419-29
LID - 10.1016/j.cmet.2009.09.006 [doi]
AB  - Chronic low-grade inflammation, particularly in adipose tissue, is an important 
      modulator of obesity-induced insulin resistance. The Toll-like receptor 4 (Tlr4) 
      is a key initiator of inflammatory responses in macrophages. We performed bone 
      marrow transplantation (BMT) of Tlr4lps-del or control C57Bl/10J donor cells into 
      irradiated wild-type C57Bl6 recipient mice to generate hematopoietic 
      cell-specific Tlr4 deletion mutant (BMT-Tlr4(-/-)) and control (BMT-WT) mice. 
      After 16 weeks of a high-fat diet (HFD), BMT-WT mice developed obesity, 
      hyperinsulinemia, glucose intolerance, and insulin resistance. In contrast, 
      BMT-Tlr4(-/-) mice became obese but did not develop fasting hyperinsulinemia and 
      had improved hepatic and adipose insulin sensitivity during euglycemic clamp 
      studies, compared to HFD BMT-WT controls. HFD BMT-Tlr4(-/-) mice also showed 
      markedly reduced adipose tissue inflammatory markers and macrophage content. In 
      summary, our results indicate that Tlr4 signaling in hematopoietic-derived cells 
      is important for the development of hepatic and adipose tissue insulin resistance 
      in obese mice.
FAU - Saberi, Maziyar
AU  - Saberi M
AD  - Department of Medicine, Division of Endocrinology and Metabolism, University of 
      California, San Diego, La Jolla, CA 92093, USA.
FAU - Woods, Niels-Bjarne
AU  - Woods NB
FAU - de Luca, Carl
AU  - de Luca C
FAU - Schenk, Simon
AU  - Schenk S
FAU - Lu, Juu Chin
AU  - Lu JC
FAU - Bandyopadhyay, Gautam
AU  - Bandyopadhyay G
FAU - Verma, Inder M
AU  - Verma IM
FAU - Olefsky, Jerrold M
AU  - Olefsky JM
LA  - eng
GR  - P01 DK074868-020001/DK/NIDDK NIH HHS/United States
GR  - DK033651/DK/NIDDK NIH HHS/United States
GR  - P01 DK074868/DK/NIDDK NIH HHS/United States
GR  - T32 DK007494-26S1/DK/NIDDK NIH HHS/United States
GR  - R37 DK033651-27/DK/NIDDK NIH HHS/United States
GR  - R01 DK033651/DK/NIDDK NIH HHS/United States
GR  - P30 DK063491/DK/NIDDK NIH HHS/United States
GR  - U54 HD 012303-25/HD/NICHD NIH HHS/United States
GR  - T32 DK007494/DK/NIDDK NIH HHS/United States
GR  - DK074868/DK/NIDDK NIH HHS/United States
GR  - P50 HD012303/HD/NICHD NIH HHS/United States
GR  - DK-063491-06/DK/NIDDK NIH HHS/United States
GR  - U54 HD012303-296875/HD/NICHD NIH HHS/United States
GR  - U54 HD012303/HD/NICHD NIH HHS/United States
GR  - R37 DK033651/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Metab
JT  - Cell metabolism
JID - 101233170
RN  - 0 (Dietary Fats)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Adipose Tissue/*metabolism/pathology
MH  - Animals
MH  - Dietary Fats/administration & dosage
MH  - Gene Knockout Techniques
MH  - Glucose Clamp Technique
MH  - Glucose Intolerance/genetics/metabolism
MH  - Hematopoietic Stem Cells/*metabolism
MH  - Insulin Resistance/*physiology
MH  - Liver/*metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Obese
MH  - Obesity/etiology/*metabolism/pathology
MH  - Organ Specificity
MH  - Signal Transduction/physiology
MH  - Toll-Like Receptor 4/*antagonists & inhibitors/genetics/*metabolism
PMC - PMC2790319
MID - NIHMS159434
EDAT- 2009/11/04 06:00
MHDA- 2010/06/16 06:00
PMCR- 2010/11/01
CRDT- 2009/11/04 06:00
PHST- 2008/10/26 00:00 [received]
PHST- 2009/05/29 00:00 [revised]
PHST- 2009/09/25 00:00 [accepted]
PHST- 2009/11/04 06:00 [entrez]
PHST- 2009/11/04 06:00 [pubmed]
PHST- 2010/06/16 06:00 [medline]
PHST- 2010/11/01 00:00 [pmc-release]
AID - S1550-4131(09)00294-0 [pii]
AID - 10.1016/j.cmet.2009.09.006 [doi]
PST - ppublish
SO  - Cell Metab. 2009 Nov;10(5):419-29. doi: 10.1016/j.cmet.2009.09.006.