Functional Role of PPARs in Ruminants: Potential Targets for Fine-Tuning Metabolism during Growth and Lactation

Table 2

PPAR isotype target genes in ruminants grouped by main biological function.

Gene	HUGO gene name	Tissue/cells^1	PPAR^2	Reference
Fatty acid import and activation
ACSL1	Acyl-CoA synthetase long-chain family member 1	MDBK	⇑ PPARα	[28, 61]
		Liver	⇑ PPARα	[78]
ACSL3	Acyl-CoA synthetase long-chain family member 3	MDBK	⇑ PPARα	[28]
CD36	Thrombospondin receptor	MDBK	⇑ PPARα	[28]
		BAEC	⇑ PPARγ	[79]
		MAC-T	⇔ PPARγ	[26]
FABP4	Fatty acid binding protein 4	Muscle	⇑ PPARγ	[80]^#
		MDBK	⇑ PPARα	[28]
		MAC-T	⇔ PPARγ	[26]
LPL	Lipoprotein lipase	sP. adipose	⇑ PPARγ	[81]
		MAC-T	⇔ PPARγ	[26]
		bS. adipose	⇔ PPARγ	[82]
Fatty acid synthesis
ACACA	Acetyl-CoA carboxylase alpha	MAC-T	⇑ PPARγ	[26]
FASN	Fatty acid synthase	MAC-T	⇑ PPARγ	[26, 83]
		bS. adipose	⇔ PPARγ	[82]
		bS. adipose	⇓ PPARγ	[84]
INSIG1	Insulin induced gene 1	MAC-T	⇑ PPARγ	[26]
SCD	Stearoyl-CoA desaturase (delta-9-desaturase)	MDBK	⇑ PPARα	[28]
SREBF1	Sterol regulatory element binding factor 1	MAC-T	⇑ PPARγ	[26]
		MDBK	⇑ PPARα	[28]
Fatty acid oxidation
ACADVL	Acyl-CoA dehydrogenase, very long chain	MDBK	⇑ PPARα	[61]
		Liver	⇑ PPARα	[78]
ACOX1	Acyl-coenzyme A oxidase 1	MDBK	⇔ PPARα	[61]
		Liver**	⇑ PPARα	[78]
CPT1A	Carnitine palmitoyltransferase 1A (liver)	MDBK	⇑ PPARα	[28, 36, 61]
		Liver**	⇑ PPARα	[78]
CPT2	Carnitine palmitoyltransferase 2	PAEC	⇑ PPARγ	[85]
CRAT	Carnitine O-acetyltransferase	PAEC	⇑ PPARγ	[85]
CYP4A11	Cytochrome P450, family 4, subfam. A, polypeptide 11	Liver	⇑ PPARα	[78]
Triacylglycerol synthesis
AGPAT6	1-acylglycerol-3-phosphate O-acyltransferase 6	MAC-T	⇑ PPARγ	[26]
DGAT1	Diacylglycerol O-acyltransferase 1	MAC-T	⇑ PPARγ	[26]
LPIN1	Lipin 1	MAC-T	⇑ PPARγ	[26]
		MDBK	⇑ PPARα	[28, 61]
LPIN3	Lipin 3	MDBK	⇑ PPARα	[28, 78]
Cholesterol synthesis
HMGCR	3-Hydroxy-3-methylglutaryl-CoA reductase	MDBK	⇑ PPARα	[28]
SREBF2	Sterol regulatory element binding transcription factor 2	MAC-T	⇑ PPARγ	[26]
Signaling molecules
ANGPTL4	Angiopoietin-like 4	Liver	⇑ PPARα	[56, 86]^++
		MDBK	⇑ PPARα	[28]
FGF21	Fibroblast growth factor 21	Liver	⇑ PPARα	[86]^++
EDN1	Endothelin 1	BAEC	⇓ PPARα	[87]
			⇓ PPARγ
LEP	Leptin	bS. adipose	⇑ PPARγ	[84]
NOS3	Nitric oxide synthase 3 (endothelial cell)	BAEC	⇑ PPARα	[88]
PTGS2	Prostaglandin-endoperoxide synthase 2	BEND	⇑ PPARα	[44]
			⇑ PPARγ	[44]
		pBESC	⇑ PPARα	[77]
		MAC-T	⇔ PPARγ	[26]
SPP1	Osteopontin	MDBK	⇑ PPARα	[28]
VEGF	Vascular endothelial growth factor	BAEC	⇑ PPARγ	[89]
Other functions
CDKN2A	Cyclin-dependent kinase inhibitor 2A	BAEC	⇓ PPARγ	[90]
GAPDH ^$	Glyceraldehyde-3-phosphate-dehydrogenase	s. ASC	⇑ PPARγ	[91]
			⇑ PPARβ/δ
OLR1	Oxidized low density lipoprotein receptor 1	BAEC	⇑ PPARα	[92]
			⇓ PPARγ	[46]
PC	Pyruvate carboxylase	Hepatoma*	⇑ PPARα	[93]
		MDBK	⇔ PPARα	[28]
SLC2A1	Solute carrier family 2, member 1	BAEC	⇓ PPAR𝛽/δ	[68]
TERF2	Telomeric repeat binding factor 2	BAEC	⇑ PPARγ	[90]
PPAR activation-related functions
PPARA	Peroxisome-proliferator-activated receptor alpha	BAEC	⇑ PPARα	[62]
		MDBK	⇔ PPARα	[28, 61]
		Liver	⇑ PPARγ	[81]
		Muscle**	⇑ PPARγ	[81]
PPARG	Peroxisome-proliferator-activated receptor gamma	bEPC	⇑ PPARγ	[94]
		MAC-T	⇔ PPARγ	[26]
PPARGC1A	PPAR𝛾, coactivator 1 alpha	s. Muscle	⇑ PPARγ	[81]

¹Acronyms: BAEC: Bovine Aortic Endothelial Cells; BEND: Bovine Endometrial Cells; bEPC: bovine renal Epithelial cells; BRCP: Bovine Retinal Capillary Pericytes; bS. Adipose: bovine subcutaneous adipose; pBESC: primary (16-day cycle) bovine endometrial stromal cells; MDBK: Madin-Darby Kidney Cell Line; PAEC: ovine pulmonary arterial endothelial cells; sP.adipose: sheep perirenal adipose; ¹s. ASC: sheep adipose stem cells; s. Muscle: sheep muscle.
²The PPAR activated by the treatment with a different effect on expression of the target gene (⇑ induction; ⇓ inhibition; ⇔ no change).
*Rat hepatoma was transfected with bovine PC promoter region.
**The increase in expression was with 𝑃<0.10 but 𝑃>0.05.
^$The activity and not the mRNA expression of GAPDH was measured.
^#Inferred based on the high correlation of expression between PPARG and FABP4.
⁺⁺Inferred based on hepatic mRNA expression in studies with peripartal cows and undernutrition ketosis [56, 86, 95] (see main body of the paper for details).