PMID- 26084695
OWN - NLM
STAT- MEDLINE
DCOM- 20151016
LR  - 20200930
IS  - 1522-1490 (Electronic)
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 309
IP  - 3
DP  - 2015 Aug 1
TI  - Selective overexpression of Toll-like receptor-4 in skeletal muscle impairs 
      metabolic adaptation to high-fat feeding.
PG  - R304-13
LID - 10.1152/ajpregu.00139.2015 [doi]
AB  - Toll-like receptor-4 (TLR-4) is elevated in skeletal muscle of obese humans, and 
      data from our laboratory have shown that activation of TLR-4 in skeletal muscle 
      via LPS results in decreased fatty acid oxidation (FAO). The purpose of this 
      study was to determine whether overexpression of TLR-4 in skeletal muscle alters 
      mitochondrial function and whole body metabolism in the context of a chow and 
      high-fat diet. C57BL/6J mice (males, 6-8 mo of age) with skeletal muscle-specific 
      overexpression of the TLR-4 (mTLR-4) gene were created and used for this study. 
      Isolated mitochondria and whole muscle homogenates from rodent skeletal muscle 
      (gastrocnemius and quadriceps) were investigated. TLR-4 overexpression resulted 
      in a significant reduction in FAO in muscle homogenates; however, mitochondrial 
      respiration and reactive oxygen species (ROS) production did not appear to be 
      affected on a standard chow diet. To determine the role of TLR-4 overexpression 
      in skeletal muscle in response to high-fat feeding, mTLR-4 mice and WT control 
      mice were fed low- and high-fat diets for 16 wk. The high-fat diet significantly 
      decreased FAO in mTLR-4 mice, which was observed in concert with elevated body 
      weight and fat, greater glucose intolerance, and increase in production of ROS 
      and cellular oxidative damage compared with WT littermates. These findings 
      suggest that TLR-4 plays an important role in the metabolic response in skeletal 
      muscle to high-fat feeding.
CI  - Copyright (c) 2015 the American Physiological Society.
FAU - McMillan, Ryan P
AU  - McMillan RP
AD  - Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, 
      Virginia; Metabolic Phenotyping Core, Virginia Tech, Blacksburg, Virginia; Fralin 
      Translational Obesity Research Center, Virginia Tech, Blacksburg, Virginia;
FAU - Wu, Yaru
AU  - Wu Y
AD  - Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, 
      Virginia;
FAU - Voelker, Kevin
AU  - Voelker K
AD  - Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, 
      Virginia;
FAU - Fundaro, Gabrielle
AU  - Fundaro G
AD  - Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, 
      Virginia;
FAU - Kavanaugh, John
AU  - Kavanaugh J
AD  - Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, 
      Virginia;
FAU - Stevens, Joseph R
AU  - Stevens JR
AD  - Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, 
      Virginia; Fralin Translational Obesity Research Center, Virginia Tech, 
      Blacksburg, Virginia;
FAU - Shabrokh, Elika
AU  - Shabrokh E
AD  - Department of Surgery, University of Michigan Medical School, Ann Arbor, 
      Michigan; and.
FAU - Ali, Mostafa
AU  - Ali M
AD  - Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, 
      Virginia;
FAU - Harvey, Mordecai
AU  - Harvey M
AD  - Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, 
      Virginia;
FAU - Anderson, Angela S
AU  - Anderson AS
AD  - Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, 
      Virginia;
FAU - Boutagy, Nabil E
AU  - Boutagy NE
AD  - Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, 
      Virginia; Fralin Translational Obesity Research Center, Virginia Tech, 
      Blacksburg, Virginia;
FAU - Mynatt, Randall L
AU  - Mynatt RL
AD  - Gene Nutrient Interactions, Pennington Biomedical Research Center, Baton Rouge, 
      Louisiana.
FAU - Frisard, Madlyn I
AU  - Frisard MI
AD  - Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, 
      Virginia; Metabolic Phenotyping Core, Virginia Tech, Blacksburg, Virginia; Fralin 
      Translational Obesity Research Center, Virginia Tech, Blacksburg, Virginia;
FAU - Hulver, Matthew W
AU  - Hulver MW
AD  - Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, 
      Virginia; Metabolic Phenotyping Core, Virginia Tech, Blacksburg, Virginia; Fralin 
      Translational Obesity Research Center, Virginia Tech, Blacksburg, Virginia; 
      hulvermw@vt.edu.
LA  - eng
GR  - 2R01 DK-078765/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150617
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Adaptation, Physiological
MH  - Animal Feed
MH  - Animals
MH  - Body Composition/physiology
MH  - Body Weight/physiology
MH  - *Diet, High-Fat
MH  - Energy Metabolism/physiology
MH  - Insulin Resistance/physiology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mitochondria/*metabolism
MH  - Muscle, Skeletal/*metabolism
MH  - Obesity/*metabolism
MH  - Toll-Like Receptor 4/*metabolism
PMC - PMC4525328
OTO - NOTNLM
OT  - Toll-like receptor 4
OT  - fatty acid oxidation
OT  - high-fat diet
OT  - reactive oxygen species
OT  - skeletal muscle
EDAT- 2015/06/19 06:00
MHDA- 2015/10/17 06:00
PMCR- 2016/08/01
CRDT- 2015/06/19 06:00
PHST- 2015/04/06 00:00 [received]
PHST- 2015/06/11 00:00 [accepted]
PHST- 2015/06/19 06:00 [entrez]
PHST- 2015/06/19 06:00 [pubmed]
PHST- 2015/10/17 06:00 [medline]
PHST- 2016/08/01 00:00 [pmc-release]
AID - ajpregu.00139.2015 [pii]
AID - R-00139-2015 [pii]
AID - 10.1152/ajpregu.00139.2015 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2015 Aug 1;309(3):R304-13. doi: 
      10.1152/ajpregu.00139.2015. Epub 2015 Jun 17.