PMID- 22824914
OWN - NLM
STAT- MEDLINE
DCOM- 20130513
LR  - 20220722
IS  - 2092-6413 (Electronic)
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 44
IP  - 10
DP  - 2012 Oct 31
TI  - Peroxisome proliferator-activated receptor delta agonist attenuates hepatic steatosis 
      by anti-inflammatory mechanism.
PG  - 578-85
LID - 10.3858/emm.2012.44.10.066 [doi]
AB  - Although peroxisome proliferator receptor (PPAR)-alpha and PPAR-gamma agonist have been 
      developed as chemical tools to uncover biological roles for the PPARs such as 
      lipid and carbohydrate metabolism, PPAR-delta has not been fully investigated. In 
      this study, we examined the effects of the PPAR-delta agonist GW0742 on fatty liver 
      changes and inflammatory markers. We investigated the effects of PPAR-delta agonist 
      GW0742 on fatty liver changes in OLETF rats. Intrahepatic triglyceride contents 
      and expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) 
      and monocyte chemo-attractant protein-1 (MCP-1) and also, PPAR-gamma coactivator 
      (PGC)-1alpha gene were evaluated in liver tissues of OLETF rats and HepG2 cells after 
      GW0742 treatment. The level of TNF-alpha and MCP-1 was also examined in supernatant 
      of Raw264. 7 cell culture. To address the effects of GW0742 on insulin signaling, 
      we performed in vitro study with AML12 mouse hepatocytes. Rats treated with 
      GW0742 (10 mg/kg/day) from 26 to 36 weeks showed improvement in fatty 
      infiltration of the liver. In liver tissues, mRNA expressions of TNF-alpha, MCP-1, 
      and PGC-1alpha were significantly decreased in diabetic rats treated with GW0742 
      compared to diabetic control rats. We also observed that GW0742 had inhibitory 
      effects on palmitic acid-induced fatty accumulation and inflammatory markers in 
      HepG2 and Raw264.7 cells. The expression level of Akt and IRS-1 was significantly 
      increased by treatment with GW0742. The PPAR-delta agonist may attenuate hepatic fat 
      accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1alpha gene 
      expression, and improvement of insulin signaling.
FAU - Lee, Mi Young
AU  - Lee MY
AD  - Department of Internal Medicine, Korea Institute of Lifestyle Medicine Yonsei 
      University Wonju College of Medicine Wonju 220-701, Korea.
FAU - Choi, Ran
AU  - Choi R
FAU - Kim, Hong Min
AU  - Kim HM
FAU - Cho, Eun Ju
AU  - Cho EJ
FAU - Kim, Bo Hwan
AU  - Kim BH
FAU - Choi, Yeon Sik
AU  - Choi YS
FAU - Naowaboot, Jarinyaporn
AU  - Naowaboot J
FAU - Lee, Eun Young
AU  - Lee EY
FAU - Yang, Young Chul
AU  - Yang YC
FAU - Shin, Jang Yel
AU  - Shin JY
FAU - Shin, Young Goo
AU  - Shin YG
FAU - Chung, Choon Hee
AU  - Chung CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Blood Glucose)
RN  - 0 (Cytokines)
RN  - 0 (PPAR delta)
RN  - 0 (Thiazoles)
RN  - 0 (Triglycerides)
RN  - 4PZK9FJC4Z 
      ((4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic 
      acid)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology/therapeutic use
MH  - Blood Glucose
MH  - Cytokines/genetics/metabolism
MH  - Diabetes Mellitus/blood/immunology/metabolism
MH  - Fatty Liver/blood/*drug therapy/immunology
MH  - Glucose Tolerance Test
MH  - Hep G2 Cells
MH  - Humans
MH  - Insulin Resistance
MH  - Liver/metabolism
MH  - Male
MH  - PPAR delta/*agonists/metabolism
MH  - Rats
MH  - Rats, Long-Evans
MH  - Thiazoles/*pharmacology/therapeutic use
MH  - Triglycerides/metabolism
PMC - PMC3490079
EDAT- 2012/07/25 06:00
MHDA- 2013/05/15 06:00
PMCR- 2012/10/31
CRDT- 2012/07/25 06:00
PHST- 2012/07/25 06:00 [entrez]
PHST- 2012/07/25 06:00 [pubmed]
PHST- 2013/05/15 06:00 [medline]
PHST- 2012/10/31 00:00 [pmc-release]
AID - emm.2012.44.066 [pii]
AID - 10.3858/emm.2012.44.10.066 [doi]
PST - ppublish
SO  - Exp Mol Med. 2012 Oct 31;44(10):578-85. doi: 10.3858/emm.2012.44.10.066.