PPAR Medicines and Human Disease: The ABCs of It All

Table 2

In vivo effects of PPAR ligands on ABC transporters.

ABC transporter	Ligand	Receptor	Model	Transporter effect	Reference
ABCA1	PPARα	Fenofibrate	Hypertriglyceridemic patients	Differential HDL synthesis due to ABCA1 variants	[87]
		WY14643	SV129 mice	↑ Abca1 mRNA and protein in intestine	[88]
				↓ intestinal absorption of cholesterol
	PPAR𝛾	Telmisartan	ApoE−/− C57BL mice	↑ Abca1 mRNA in aorta	[63]
				↓ atherosclerotic lesion size and number
Pgp/MDR1/ABCB1	PPARα	Ciprofibrate	SV129 mice	↑ hepatic Mdr1 & Mdr3 mRNA	[73]
MDR2/MDR3/ABCB4	PPAR𝛼	Bezafibrate	CF1 mice	↑ hepatic Mdr2 mRNA	[78]
				↑ bile secretion of phospholipid
			Humanized liver-uPA/SCID chimeric mice	↑ hepatic MDR2/MDR3 mRNA and protein	[71]
				↑ hepatic MDR2/MDR3 redistribution into bile canaliculi
		Ciprofibrate	SV129 mice	↑ hepatic Mdr2 mRNA and protein	[73]
				↑ bile secretion of cholesterol and phospholipids
			CF1 mice	↑ hepatic Mdr2 mRNA	[78]
				↑ Mdr2 redistribution into bile canaliculi
				↑ bile secretion of phospholipid
		Clofibrate	CF1 mice	↑ hepatic Mdr2 mRNA	[78]
				↑ Mdr2 redistribution into bile canaliculi
				↑ bile secretion of phospholipid
		Fenofibrate	CF1 mice	↑ hepatic Mdr2 mRNA	[78]
		Gemfibrozil	CF1 mice	↑ hepatic Mdr2 mRNA	[78]
MRP1/ABCC1	PPAR𝛼	Ciprofibrate	C57BL mice	↓ hepatic Mrp1 mRNA	[83]
		Clofibrate	C57BL mice	↓ hepatic Mrp1 mRNA	[83]
		GW7647	C57BL mice	↓ Mrp1 mRNA in small intestine	[85]
		WY14643	C57BL mice	↓ Mrp1 mRNA in small intestine	[85]
MRP2/ABCC2	PPAR𝛼	Clofibrate	Sprague-Dawley rats	↓ hepatic Mrp2 protein	[89]
		DEHP	Sprague-Dawley rats	↓ hepatic Mrp2 protein	[89]
		PFDA	Sprague-Dawley rats	↓ hepatic Mrp2 protein	[89]
MRP3/ABCC3	PPAR𝛼	Ciprofibrate	C57BL mice	↑ hepatic Mrp3 mRNA	[83]
		Clofibrate	C57BL mice	↑ hepatic Mrp3 mRNA	[83]
			CD1 mice	↑ hepatic Mrp3 mRNA and protein	[82]
			SV129 mice
		DEHP	C57BL mice	↑ hepatic Mrp3 mRNA	[83]
		PFDA	C57BL mice	↑ hepatic Mrp3 mRNA	[84]
				↑ serum levels of bilirubin and bile acids
MRP4/ABCC4	PPAR𝛼	Clofibrate	CD1 mice	↑ hepatic Mrp4 mRNA and protein	[82]
			SV129 mice
		PFDA	C57BL mice	↑ hepatic Mrp3 mRNA	[84]
				↑ serum levels of bilirubin and bile acids
ABCG1	PPAR𝛼	Fenofibrate	Zucker diabetic fatty rats	↑ Abcg1 mRNA	[90]
				↑ HDL particle size
	PPAR𝛾	Telmisartan	ApoE−/− C57BL mice	↑ Abcg1 mRNA in aorta	[63]
				↓ atherosclerotic lesion size and number
BCRP/ABCG2	PPAR𝛼	Clofibrate	CD1 mice	↑ hepatic Bcrp mRNA and protein	[82]
			SV129 mice	↑ hepatic Bcrp mRNA	[82]
		GW7647	C57BL mice	↑ Bcrp mRNA in small intestine	[85]
		WY14643	C57BL mice	↑ Bcrp mRNA in small intestine	[85]