PPARdelta ligand L-165041 ameliorates Western diet-induced hepatic lipid accumulation and inflammation in LDLR-/- mice.
Although peroxisome proliferator-activated receptor delta (PPARdelta) has been implicated in energy metabolism and lipid oxidation process, detailed roles of PPARdelta in lipid homeostasis under pathologic conditions still remain controversial. Thus, we investigated the effect of PPARdelta ligand L-165041 on Western diet-induced fatty liver using low-density lipoprotein receptor-deficient (LDLR(-/-)) mice. LDLR(-/-) mice received either L-165041 (5mg/kg/day) or vehicle (0.1N NaOH) with Western diet for 16 weeks. According to our data, L-165041 drastically reduced lipid accumulation in the liver, decreasing total hepatic cholesterol and triglyceride content compared to the vehicle group. Gene expression analysis demonstrated that L-165041 lowered hepatic expression of PPARgamma, apolipoprotein B, interleukin 1 beta (IL-1beta), and interleukin-6. In contrast, L-165041 increased hepatic expressions of PPARdelta, lipoprotein lipase (LPL), and ATP-binding cassette transporter G1 (ABCG1). Our data suggest that L-165041 might be effective in preventing Western diet-induced hepatic steatosis by regulating genes involved in lipid metabolism and the inflammatory response.
Lim
Hyun-Joung
HJ
Division of Cardiovascular and Rare Diseases, Center for Biomedical Sciences, National Institute of Health, Republic of Korea.
Park
Jin-Hee
JH
Lee
Seahyoung
S
Choi
Hye-Eun
HE
Lee
Kuy-Sook
KS
Park
Hyun-Young
HY
D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D004032:Diet / Q000009:adverse effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008024:Ligands; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D010642:Phenoxyacetates / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism
C520164:4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid; D001055:Apolipoproteins B; D016207:Cytokines; D008024:Ligands; D047494:PPAR delta; D010642:Phenoxyacetates; D012333:RNA, Messenger; D011973:Receptors, LDL; D014280:Triglycerides; D002784:Cholesterol