Team players in the pathogenesis of metabolic dysfunctions-associated steatotic liver disease: The basis of development of pharmacotherapy

Table 1 Peroxisome proliferator-activated receptor-α functions[101]

Organ/tissue	Positive regulation	Negative regulation
Liver	↑ ApoAI; ↑ ApoAII; ↑ ApoAV	↓ Apoptosis
	↑ Cholesterol catabolism	↓ HL
	↑ FA oxidation and activation	↓ Inflammation
	↑ Fatty acid oxidation genes	↓ Oxidative stress
	↑ FATP; ↑ FAT/CD3	↓ Proteolysis of SREBF1
	↑ Gluconeogenesis and glycolysis	↓ SREBF2
	↑ Insig1
	↑ Ketogenesis
	↑ Lipogenesis
	↑ LPL and triglyserides clearance
Skeletal muscle	↑ FA oxidation gene	↓ Glucose intolerance
	↑ FA oxidation
	↑ Insulin sensitivity
Cardiac muscle	↑ AT2 receptor	↓ AT1 receptor
	↑ FA uptake	↓ Cardiac hypertrophy and inflammation
	↑ FA oxidation	↓ Genes for glucose uptake and oxidation
		↓ ED-1 (CD68) expression
		↓ NF-κB activity
		↓ VCAM-1, ICAM-1
		↓ Platelet and endothelial cell adhesion
Plasma	↑ HDL	↓ ApoC3
	↑ RCT	↓ Dyslipidemia
		↓ Inflammation
		↓ IFN-γ
		↓ TNFα
		↓ sdLDL
		↓ VLDL-triglyserides

Apo: Apoprotein; AT1: Endothelin-1 receptor; AT2: Endothelin-2 receptor; IFN-γ: Interferon gamma; FA: Fatty acid; FATP: Fatty acid transport protein; ICAM-1: Insig-1: Insulin induced gene-1; LPL: Lipoprotein lipase; RCT: Reverse cholesterol transport; sdLDL: Small-dense LDL; VCAM-1: Vascular cell adhesion molecules-1; TNFα: Tumor necrosis factor-alpha.