PMID- 24815961
OWN - NLM
STAT- MEDLINE
DCOM- 20150804
LR  - 20220409
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 5
DP  - 2014 May 12
TI  - Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and 
      insulin resistance.
PG  - 3878
LID - 10.1038/ncomms4878 [doi]
AB  - Chronic low-grade inflammation is a hallmark of obesity and thought to contribute 
      to the development of obesity-related insulin resistance. Toll-like receptor 4 
      (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are 
      protected from diet-induced insulin resistance and inflammation; however, which 
      Tlr4-expressing cells mediate this effect is unknown. Here we show that mice 
      deficient in hepatocyte Tlr4 (Tlr4LKO) exhibit improved glucose tolerance, 
      enhanced insulin sensitivity and ameliorated hepatic steatosis despite the 
      development of obesity after a high-fat diet (HFD) challenge. Furthermore, 
      Tlr4LKO mice have reduced macrophage content in white adipose tissue, as well as 
      decreased tissue and circulating inflammatory markers. In contrast, the loss of 
      Tlr4 activity in myeloid cells has little effect on insulin sensitivity. 
      Collectively, these data indicate that the activation of Tlr4 on hepatocytes 
      contributes to obesity-associated inflammation and insulin resistance, and 
      suggest that targeting hepatocyte Tlr4 might be a useful therapeutic strategy for 
      the treatment of type 2 diabetes.
FAU - Jia, Lin
AU  - Jia L
AD  - 1] Division of Hypothalamic Research, Department of Internal Medicine, University 
      of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA [2].
FAU - Vianna, Claudia R
AU  - Vianna CR
AD  - 1] Division of Hypothalamic Research, Department of Internal Medicine, University 
      of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA [2].
FAU - Fukuda, Makoto
AU  - Fukuda M
AD  - 1] Division of Hypothalamic Research, Department of Internal Medicine, University 
      of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA [2].
FAU - Berglund, Eric D
AU  - Berglund ED
AD  - 1] Department of Pharmacology, University of Texas Southwestern Medical Center at 
      Dallas, Dallas, Texas 75390, USA [2] Advanced Imaging Research Center, University 
      of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
FAU - Liu, Chen
AU  - Liu C
AD  - Division of Hypothalamic Research, Department of Internal Medicine, University of 
      Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
FAU - Tao, Caroline
AU  - Tao C
AD  - Touchstone Diabetes Center, University of Texas Southwestern Medical Center, 
      Dallas, Texas 75390, USA.
FAU - Sun, Kai
AU  - Sun K
AD  - Touchstone Diabetes Center, University of Texas Southwestern Medical Center, 
      Dallas, Texas 75390, USA.
FAU - Liu, Tiemin
AU  - Liu T
AD  - Division of Hypothalamic Research, Department of Internal Medicine, University of 
      Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
FAU - Harper, Matthew J
AU  - Harper MJ
AD  - Division of Hypothalamic Research, Department of Internal Medicine, University of 
      Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
FAU - Lee, Charlotte E
AU  - Lee CE
AD  - Division of Hypothalamic Research, Department of Internal Medicine, University of 
      Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
FAU - Lee, Syann
AU  - Lee S
AD  - Division of Hypothalamic Research, Department of Internal Medicine, University of 
      Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
FAU - Scherer, Philipp E
AU  - Scherer PE
AD  - Touchstone Diabetes Center, University of Texas Southwestern Medical Center, 
      Dallas, Texas 75390, USA.
FAU - Elmquist, Joel K
AU  - Elmquist JK
AD  - 1] Division of Hypothalamic Research, Department of Internal Medicine, University 
      of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA [2] 
      Department of Pharmacology, University of Texas Southwestern Medical Center at 
      Dallas, Dallas, Texas 75390, USA.
LA  - eng
GR  - P01 DK088761/DK/NIDDK NIH HHS/United States
GR  - RL9 DK081180/DK/NIDDK NIH HHS/United States
GR  - P01-DK088761/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140512
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Adipose Tissue, White/cytology/immunology
MH  - Animals
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Type 2/etiology
MH  - Diet, High-Fat
MH  - Enzyme Activation
MH  - Fatty Liver/genetics
MH  - Glucose Tolerance Test
MH  - Hepatocytes/*enzymology
MH  - Inflammation/*immunology
MH  - Insulin Resistance/genetics/*immunology
MH  - Liver/cytology/pathology
MH  - Macrophages/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Obesity/*immunology/metabolism
MH  - Toll-Like Receptor 4/genetics/*metabolism
PMC - PMC4080408
MID - NIHMS585593
EDAT- 2014/05/13 06:00
MHDA- 2015/08/05 06:00
PMCR- 2014/11/12
CRDT- 2014/05/13 06:00
PHST- 2014/02/28 00:00 [received]
PHST- 2014/04/11 00:00 [accepted]
PHST- 2014/05/13 06:00 [entrez]
PHST- 2014/05/13 06:00 [pubmed]
PHST- 2015/08/05 06:00 [medline]
PHST- 2014/11/12 00:00 [pmc-release]
AID - ncomms4878 [pii]
AID - 10.1038/ncomms4878 [doi]
PST - epublish
SO  - Nat Commun. 2014 May 12;5:3878. doi: 10.1038/ncomms4878.