PMID- 25063273
OWN - NLM
STAT- MEDLINE
DCOM- 20150706
LR  - 20211021
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 57
IP  - 10
DP  - 2014 Oct
TI  - PPARbeta/delta prevents endoplasmic reticulum stress-associated inflammation and insulin 
      resistance in skeletal muscle cells through an AMPK-dependent mechanism.
PG  - 2126-35
LID - 10.1007/s00125-014-3331-8 [doi]
AB  - AIM/HYPOTHESIS: Endoplasmic reticulum (ER) stress, which is involved in the link 
      between inflammation and insulin resistance, contributes to the development of 
      type 2 diabetes mellitus. In this study, we assessed whether peroxisome 
      proliferator-activated receptor (PPAR)beta/delta prevented ER stress-associated 
      inflammation and insulin resistance in skeletal muscle cells. METHODS: Studies 
      were conducted in mouse C2C12 myotubes, in the human myogenic cell line LHCN-M2 
      and in skeletal muscle from wild-type and PPARbeta/delta-deficient mice and mice exposed 
      to a high-fat diet. RESULTS: The PPARbeta/delta agonist GW501516 prevented lipid-induced 
      ER stress in mouse and human myotubes and in skeletal muscle of mice fed a 
      high-fat diet. PPARbeta/delta activation also prevented thapsigargin- and 
      tunicamycin-induced ER stress in human and murine skeletal muscle cells. In 
      agreement with this, PPARbeta/delta activation prevented ER stress-associated 
      inflammation and insulin resistance, and glucose-intolerant PPARbeta/delta-deficient 
      mice showed increased phosphorylated levels of inositol-requiring 1 transmembrane 
      kinase/endonuclease-1alpha in skeletal muscle. Our findings demonstrate that PPARbeta/delta 
      activation prevents ER stress through the activation of AMP-activated protein 
      kinase (AMPK), and the subsequent inhibition of extracellular-signal-regulated 
      kinase (ERK)1/2 due to the inhibitory crosstalk between AMPK and ERK1/2, since 
      overexpression of a dominant negative AMPK construct (K45R) reversed the effects 
      attained by PPARbeta/delta activation. CONCLUSIONS/INTERPRETATION: Overall, these 
      findings indicate that PPARbeta/delta prevents ER stress, inflammation and insulin 
      resistance in skeletal muscle cells by activating AMPK.
FAU - Salvado, Laia
AU  - Salvado L
AD  - Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, 
      University of Barcelona, Diagonal 643, 08028, Barcelona, Spain.
FAU - Barroso, Emma
AU  - Barroso E
FAU - Gomez-Foix, Anna Maria
AU  - Gomez-Foix AM
FAU - Palomer, Xavier
AU  - Palomer X
FAU - Michalik, Liliane
AU  - Michalik L
FAU - Wahli, Walter
AU  - Wahli W
FAU - Vazquez-Carrera, Manuel
AU  - Vazquez-Carrera M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140726
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (PPAR delta)
RN  - 0 (PPAR-beta)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Cell Line
MH  - Diet, High-Fat/adverse effects
MH  - Endoplasmic Reticulum Stress/genetics/*physiology
MH  - Humans
MH  - In Vitro Techniques
MH  - Inflammation/etiology/genetics/*metabolism
MH  - Insulin Resistance/genetics/*physiology
MH  - Mice
MH  - Muscle Fibers, Skeletal/metabolism
MH  - Muscle, Skeletal/*metabolism
MH  - PPAR delta/deficiency/genetics/*physiology
MH  - PPAR-beta/deficiency/genetics/*physiology
EDAT- 2014/07/27 06:00
MHDA- 2015/07/07 06:00
CRDT- 2014/07/27 06:00
PHST- 2014/05/14 00:00 [received]
PHST- 2014/06/26 00:00 [accepted]
PHST- 2014/07/27 06:00 [entrez]
PHST- 2014/07/27 06:00 [pubmed]
PHST- 2015/07/07 06:00 [medline]
AID - 10.1007/s00125-014-3331-8 [doi]
PST - ppublish
SO  - Diabetologia. 2014 Oct;57(10):2126-35. doi: 10.1007/s00125-014-3331-8. Epub 2014 
      Jul 26.