TABLE 2

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.

Compound	Primary Action	ABCA1		ABCG1		Cholesterol Efflux		Reference
PPARγ-activating compounds
15d-PGJ2	Prostanoid-specific receptor inhibitor	↑	THP-1	↑	PM^{^a}		Lipid-loaded HMC	Ruan et al., 2003; Jiang and Li, 2017
		↑	HMC			↑	apoA-I
		↓↓	PM^{^a}				PM^{^a}
						↓	apoA-I
						↑	HDL
4010B-30	Benzamide analog	↑	RAW264.7		—		RAW264.7	Du et al., 2015b
4010B-30	Benzamide analog	↑	HepG2		—	↑	apoA-I	Du et al., 2015b
Ciglitazone	PPARγ agonist	↑=	THP-1	↑	THP-1	↑	THP-1	Argmann et al., 2003, 2005
E3317	PPARγ agonist		RAW264.7				RAW264.7	Wang et al., 2018
E3317	PPARγ agonist	↑↑	LO2			↑	apoA-I	Wang et al., 2018
GQ-11	PPARγ/α agonist	↑	Liver^{^b}					Silva et al., 2018
GW1929	PPARγ agonist	↑↑	HepG2		—		—	Mogilenko et al., 2010
GW7845	PPARγ agonist	↑	THP-1		—	↑	THP-1	Chawla et al., 2001; Oliver et al., 2001
Propofol	GABA_B receptor agonist	↑↑	THP-1	↑↑	THP-1	↑	THP-1	Ma et al., 2015; Hsu et al., 2018
		↑	RAECs				RAECs
						↑	HDL
Lysophosphatidylcholine	Unknown	↑↑	PM^{^a}		—	↑	PM^{^a}	Hou et al., 2007
Mycophenolic acid	Inosine-5′-monophosphate dehydrogenase inhibitor	↑↑	HepG2		—		—	Xu et al., 2011
Pioglitazone	PPARγ agonist	↑↑	THP-1	↑↑	THP-1		THP-1	Panzenboeck 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
		↑	HepG2	↑	Monocyte-derived macrop	↑	apoA-I
		↑↑	pBCECs	↑	PM^{^a}	↑	HDL
		↑	gBECs	↑	Diabetic patients^{^c}	↓	pBCECs
		↑↑	WI38 fibroblasts	↑	Rat cortical neurons	↑	gBECs
		↑	Monocyte-derived macrop^{^c}			↑	WI38 fibroblasts
		↓↓	PM^{^a}				PM^{^a}
		=	Liver^{^b}			↓	apoA-I
		↑	Diabetic patients^{^c}			↑	HDL
		↑	Rat cortical neurons			↑	Diabetic patients^{^c}

Rosiglitazone	PPARγ agonist	↑↑	THP-1	↑↑	THP-1	↑	THP	Chawla et al., 2001; Chinetti et al., 2001; Claudel et al., 2001; Li et al., 2004, 2015; Llaverias et al., 2006
		↑	RAW264.7	↑	macrop^{^d}	↑	RAW264.7
		↑	HepG2	↑	Aorta^{^d}	↑	macrop^{^d}
		==	macrop^{^d}			↑	PM^{^e}
		↑	PM^{^e}			↑	Hepatocytes^{^e}
		↑=	Hepatocytes^{^e}
		=	Aorta^{^d}
			Aorta lesion^{^e}
Telmisartan	Angiotensin receptor 1 antagonist	↑↑	THP-1	↑↑	THP-1	↑	THP-1	Nakaya et al., 2007
Telmisartan	Angiotensin receptor 1 antagonist	↑	Monocyte-derived macrop^{^c}	↑	Monocyte-derived macrop^{^c}	↑	THP-1	Nakaya et al., 2007
Troglitazone	PPARγ agonist	↑	THP-1	↑	PM^{^a}	↑	pBCECs	Cabrero et al., 2003; Panzenboeck et al., 2006; Lee et al., 2008; Jiang and Li, 2017
		↓↑	pBCECs				PM^{^a}
		↑↑	gBECs			↓	apoA-I
		=	Monocyte-derived macrop^{^c}			↑	HDL
		↓↓	PM^{^a}
PPARα-activating compounds
Aspirin	COX-1/2 inhibitor	↑	THP-1		—		RAW264.7	Viñals et al., 2005; Wang et al., 2010
Aspirin	COX-1/2 inhibitor	↑↑	RAW264.7		—	↑	apoA-I	Viñals et al., 2005; Wang et al., 2010
Atorvastatin	HMG-CoA reductase inhibitor	↑	THP-1	↑	THP-1		THP-1	Argmann et al., 2005; Maejima et al., 2011; Nicholls et al., 2015, 2017
		↑	McARH7777			↑	apoA-I
						↑	HDL
Bezafibrate	Pan-PPAR agonist	↑↑	THP-1		—	↑	THP-1	Cabrero et al., 2003; Ruan et al., 2003; Panzenboeck et al., 2006; Hossain et al., 2008; Inaba et al., 2008; Ogata et al., 2009
		↑↑	HepG2			↑	HepG2
		==	pBCECs			=	pBCECs
		↑↑	W138 fibroblast			↑	W138 fibroblast
		↑	HMC				Lipid-loaded HMC
		↑↑	Primary hepatocytes			↑	apoA-I
		=	Monocyte-derived macrop^{^c}			↑	Primary hepatocytes
		=	aorta^{^b}
Clofibrate	PPARα agonist	↑=	HepG2		—		—	Guan et al., 2003; Kobayashi et al., 2011
		=	Primary hepatocytes^{^f}
		↑	Liver^{^f}
Fenofibrate	PPARα agonist	↑↑	THP-1	↑	Liver^{^g}	↑	THP-1	Forcheron 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
		↑↑	RAW264.7			↑	RAW264.7
		↑↑	HepG2			↑	HepG2
		=↑	pBCECs			=	pBCECs
		↑↑	Balb/3T3			=	Balb/3T3
		↑↑	W138 fibroblast			↑	W138 fibroblast
		↑↑	Primary hepatocytes			↑	Primary hepatocytes
		=	Monocyte-derived macrop^{^c}
		↑	PM^{^a}
		↑	Liver^{^h}
		↑	Diabetic patients^{^c}
		↑	Aorta^ⁱ
Gemfibrozil	PPARα agonist	↑↑	THP-1		—	↑	THP-1	Hossain et al., 2008; Ogata et al., 2009
		↑↑	HepG2			↑	HepG2
		↑↑	W138 fibroblast			↑	W138 fibroblast
		↑↑	Primary hepatocytes			↑	Primary hepatocytes
GW7647	PPARα agonist	↑	THP-1	=	macrop^{^d}	=	THP-1	Oliver et al., 2001; Li et al., 2004; Wang et al., 2010; Nakaya et al., 2011
		↑↑	RAW264.7	=	Aorta^{^d}		RAW264.7
		==	macrop^{^d}	↑↑	BMM^{^a}	↑	apoA-I
		==	Atherosclerotic lesion^{^d}			=	macrop^{^d}
		↑↑	BMM^{^a}			↑	BMM^{^a}
LY518674	PPARα agonist	↑↑	THP-1		—	↑	THP-1	Hossain et al., 2008; Ogata et al., 2009
		↑↑	HepG2			↑	HepG2
		↑↑	W138 fibroblast			↑	W138 fibroblast
		↑↑	Primary hepatocytes			↑	Primary hepatocytes
Pitavastatin	HMG-CoA reductase inhibitor	↓	J774		—	↓	J774	Zanotti et al., 2004, 2006; Kobayashi et al., 2011; Maejima et al., 2011
		↑	HepG2			↑	Fu5AH
		↑↑	McARH7777			↓	PM^{^a}^,^{^b}^,^{^d}
		↑	Liver^{^f}			=	LXR^−/− mice
Pravastatin	HMG-CoA reductase inhibitor	↑↑	3T3-L1	↓↓	3T3-L1	↓	3T3-L1	Maejima et al., 2011; Mostafa et al., 2016
Pravastatin	HMG-CoA reductase inhibitor	=	McARH7777	↓↓	3T3-L1	↓	3T3-L1	Maejima et al., 2011; Mostafa et al., 2016
Rosuvastatin	HMG-CoA reductase inhibitor	=	Hepatocytes^{^a}			↑	J774	Shimizu et al., 2014; Mostafa et al., 2016
						↑	BMM^{^a}	Shimizu et al., 2014; Mostafa et al., 2016
						↑	RCT^{^a}
Simvastatin	HMG-CoA reductase inhibitor	↑	McARH7777	==	PM^ⁱ		THP-1	Argmann 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	==	Liver^ⁱ	↑	apoA-I
		==	PM^{^d}			=	HDL
		↑↑	Liver^ⁱ			↑	RAW264.7
WY14643	PPARα agonist	↑↑	THP-1	↑	THP-1	↑	THP-1	Chinetti et al., 2001; Ruan et al., 2003; Beyer et al., 2004; Arakawa et al., 2005; Lee et al., 2008; Maejima et al., 2011
		↑↑	RAW264.7			↑	RAW264.7
		↑↑	gBECs			=	Balb/3T3
		↑↑	Balb/3T3				Lipid-loaded HMC
		=	McARH7777			↑	apoA-I
		↑	Liver^{^a}
Wy,14,563	PPARα agonist		—		—	↑	THP-1	Chawla et al., 2001
PPARδ/β-activating compounds
Carbaprostacyclin (cPGI)	PPARδ agonist		—		—	↑	THP-1	Chawla et al., 2001
GW0742	PPARδ agonist	=	Liver^{^a}	=	Liver^{^a}	↑	BMM^{^a}	Li et al., 2004; Briand et al., 2009
		=	Small intestine^{^a}	=	Small intestine^{^a}	=	macrop^{^a}
		==	macrop^{^d}	=	macrop^{^d}
		=	Atherosclerotic lesion^{^d}	=	Aorta^{^d}
GW501515	PPARδ agonist	↑↑	THP-1	=	HSKM	↑	THP-1	Oliver et al., 2001; Sprecher et al., 2007; Ogata et al., 2009
		↑↑	W138 fibroblast			↑	W138 fibroblast
		↑	1BR3N fibroblast			↑	1BR3N fibroblast
		↑	Intestinal FHS74			↑	Intestinal
		↑	HSKM				HSKM

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.