PPAR-activating compounds

Overview of compounds that activate PPARs, including their primary pharmacological action, effects on ABCA1 and ABCG1 expression (arrows: mRNA, protein), and effects on cellular cholesterol efflux. Effects on ABCA1, ABCG1, and cholesterol efflux are presented as follows: (↓) decreased; (= ) no effect; (↑) increased. Italicized symbols indicate changes in ABCA1 and ABCG1 mRNA levels, whereas nonitalicized symbols indicate protein levels.

CompoundPrimary ActionABCA1ABCG1Cholesterol EffluxReference
PPARγ-activating compounds
15d-PGJ2Prostanoid-specific receptor inhibitorTHP-1PMaLipid-loaded HMCRuan et al., 2003; Jiang and Li, 2017
HMC apoA-I
4010B-30Benzamide analogRAW264.7RAW264.7Du et al., 2015b
HepG2 apoA-I
CiglitazonePPARγ agonist↑=THP-1THP-1THP-1Argmann et al., 2003, 2005
E3317PPARγ agonistRAW264.7RAW264.7Wang et al., 2018
LO2 apoA-I
GQ-11PPARγ/α agonistLiverbSilva et al., 2018
GW1929PPARγ agonistHepG2Mogilenko et al., 2010
GW7845PPARγ agonistTHP-1THP-1Chawla et al., 2001; Oliver et al., 2001
PropofolGABAB receptor agonistTHP-1THP-1THP-1Ma et al., 2015; Hsu et al., 2018
LysophosphatidylcholineUnknownPMaPMaHou et al., 2007
Mycophenolic acidInosine-5′-monophosphate dehydrogenase inhibitorHepG2Xu et al., 2011
PioglitazonePPARγ agonistTHP-1THP-1THP-1Panzenboeck et al., 2006; Nakaya et al., 2007; Tanabe et al., 2008; Ogata et al., 2009; Cocks et al., 2010; Ozasa et al., 2011; Wang et al., 2014b, 2015b; Jiang and Li, 2017; Silva et al., 2018
HepG2Monocyte-derived macrop apoA-I
gBECsDiabetic patientscpBCECs
WI38 fibroblastsRat cortical neuronsgBECs
Monocyte-derived macropcWI38 fibroblasts
=Liverb apoA-I
Diabetic patientsc HDL
Rat cortical neuronsDiabetic patientsc
RosiglitazonePPARγ agonistTHP-1THP-1THPChawla et al., 2001; Chinetti et al., 2001; Claudel et al., 2001; Li et al., 2004, 2015; Llaverias et al., 2006
Aorta lesione
TelmisartanAngiotensin receptor 1 antagonistTHP-1THP-1THP-1Nakaya et al., 2007
Monocyte-derived macropcMonocyte-derived macropc
TroglitazonePPARγ agonistTHP-1PMapBCECsCabrero et al., 2003; Panzenboeck et al., 2006; Lee et al., 2008; Jiang and Li, 2017
gBECs apoA-I
=Monocyte-derived macropc HDL
PPARα-activating compounds
AspirinCOX-1/2 inhibitorTHP-1RAW264.7Viñals et al., 2005; Wang et al., 2010
AtorvastatinHMG-CoA reductase inhibitorTHP-1THP-1THP-1Argmann et al., 2005; Maejima et al., 2011; Nicholls et al., 2015, 2017
McARH7777 apoA-I
BezafibratePan-PPAR agonistTHP-1THP-1Cabrero et al., 2003; Ruan et al., 2003; Panzenboeck et al., 2006; Hossain et al., 2008; Inaba et al., 2008; Ogata et al., 2009
W138 fibroblastW138 fibroblast
HMCLipid-loaded HMC
Primary hepatocytes apoA-I
=Monocyte-derived macropcPrimary hepatocytes
ClofibratePPARα agonist=HepG2Guan et al., 2003; Kobayashi et al., 2011
=Primary hepatocytesf
FenofibratePPARα agonistTHP-1LivergTHP-1Forcheron et al., 2002; Lin and Bornfeldt, 2002; Cabrero et al., 2003; Thomas et al., 2003; Arakawa et al., 2005; Kooistra et al., 2006; Hossain et al., 2008; Tanabe et al., 2008; Ogata et al., 2009; Jiang and Li, 2017
W138 fibroblastW138 fibroblast
Primary hepatocytesPrimary hepatocytes
=Monocyte-derived macropc
Diabetic patientsc
GemfibrozilPPARα agonistTHP-1THP-1Hossain et al., 2008; Ogata et al., 2009
W138 fibroblastW138 fibroblast
Primary hepatocytesPrimary hepatocytes
GW7647PPARα agonistTHP-1=macropd=THP-1Oliver et al., 2001; Li et al., 2004; Wang et al., 2010; Nakaya et al., 2011
==macropdBMMa apoA-I
==Atherosclerotic lesiond=macropd
LY518674PPARα agonistTHP-1THP-1Hossain et al., 2008; Ogata et al., 2009
W138 fibroblastW138 fibroblast
Primary hepatocytesPrimary hepatocytes
PitavastatinHMG-CoA reductase inhibitorJ774J774Zanotti et al., 2004, 2006; Kobayashi et al., 2011; Maejima et al., 2011
Liverf=LXR−/− mice
PravastatinHMG-CoA reductase inhibitor3T3-L13T3-L13T3-L1Maejima et al., 2011; Mostafa et al., 2016
RosuvastatinHMG-CoA reductase inhibitor=HepatocytesaJ774Shimizu et al., 2014; Mostafa et al., 2016
SimvastatinHMG-CoA reductase inhibitorMcARH7777==PMiTHP-1Argmann et al., 2005; Guan et al., 2008; Maejima et al., 2011; Song et al., 2011; Ying et al., 2013; Gong et al., 2014
Diabetic patients with hyperlipidemia==Liveri apoA-I
==PMd= HDL
WY14643PPARα agonistTHP-1THP-1THP-1Chinetti et al., 2001; Ruan et al., 2003; Beyer et al., 2004; Arakawa et al., 2005; Lee et al., 2008; Maejima et al., 2011
Balb/3T3Lipid-loaded HMC
=McARH7777 apoA-I
Wy,14,563PPARα agonistTHP-1Chawla et al., 2001
PPARδ/β-activating compounds
Carbaprostacyclin (cPGI)PPARδ agonistTHP-1Chawla et al., 2001
GW0742PPARδ agonist=Livera=LiveraBMMaLi et al., 2004; Briand et al., 2009
=Small intestinea=Small intestinea=macropa
=Atherosclerotic lesiond=Aortad
GW501515PPARδ agonistTHP-1=HSKMTHP-1Oliver et al., 2001; Sprecher et al., 2007; Ogata et al., 2009
W138 fibroblastW138 fibroblast
1BR3N fibroblast1BR3N fibroblast
Intestinal FHS74Intestinal
  • BMM, bone marrow– derived macrophage; gBECS, gallbladder epithelial cells; HMC, human mast cell; HSKM, human skeletal muscle cell; macrop, macrophage; pBCECs, porcine brain capillary endothelial cells; PM, peritoneal macrophages; RAECs, rat aortic endothelial cells.

  • a C75BL/6 mice.

  • b LDLR−/− C75BL/6 mice.

  • c Human.

  • d LDLR−/− C75BL/6 hypercholesterolemic mice.

  • e New Zealand White rabbits.

  • f Male Wistar rats.

  • g Male Zucker diabetic fatty rats.

  • h 129SV mice.

  • i Female E3L transgenic mice.