. 2023 May 24;15(11):2452. doi: 10.3390/nu15112452

Table 1.

Selected mechanisms of action of exercise on hepatic steatosis.

Mechanism of Action	Effects on Hepatic Steatosis	Animal Evidence	Human Evidence	Extrahepatic Benefits	Safety
AMPK	↓ steatosis	Aerobic and resistance training increases AMPK activation	N.A.	↑ GLUT-4 expression	Exercise is safe for people with NAFLD/NASH when supervised by an appropriately qualified exercise professional and with adequate screening and monitoring protocols.
AMPK	↓ steatosis	Aerobic and resistance training increases AMPK activation	N.A.	↑ glucose uptake
FGF-19 and -21	↓ steatosis	Aerobic exercise training increases FGF receptor 1 and FGF receptor 2 Chronic exercise training increases β-klotho Chronic exercise training reduces serum FGF-21	Aerobic and resistance training reduces serum FGF-21	↑ hepatic glycogen synthesis
FGF-19 and -21	↓ steatosis		Effect of exercise on FGF-19 is unclear	↑ hepatic gluconeogenesis
GLP-1	↓ steatosis	N.A.	Acute aerobic exercise ↑ GLP-1	↑ weight loss
			Short term high-intensity aerobic exercise reversed GLP-1 resistance	↑ insulin production
			N.A. for chronic training adaptation	↓ appetite
Mitochondrial function and β-oxidation	↓ steatosis	Exercise training improves mitochondrial function, ↑ mitochondrial content and ↑ β-oxidation	Exercise training improves mitochondrial function, ↑ mitochondrial content and ↑ β-oxidation	↑ insulin sensitivity
UCP	↓ steatosis	Aerobic exercise upregulates UCP-1 and reverses UCP-2 dysfunction in the liver	N.A.	Prevent oxidative stress
PPAR-α/γ	↓ steatosis	Exercise training (moderate-intensity running or swimming; high-intensity interval training; resistance training) activates PPAR-α	N.A.	↑ insulin sensitivity
PPAR-α/γ	↓ steatosis	Maternal aerobic exercise may protect against early life NAFLD in offspring	N.A.	↑ insulin sensitivity
THR-β	↓ steatosis	Aerobic exercise training increases T3 response index	N.A.	Acute exercise ↑ free T3 and T4
				↑ mitochondria size and number
				↑ glucose uptake
				↑ gluconeogenesis
				Chronic exercise ↑ T3 and T4 turnover at same absolute intensity

AMPK = adenosine monophosphate-activated protein kinase; FGF = fibroblast growth factor; GLP = glucagon-like peptide; GLUT = glucose transporter type; N.A. = not available; NAFLD = nonalcoholic fatty liver disease; NASH = nonalcoholic steatohepatitis; PPAR = peroxisome proliferator-activated receptor; T3 = triiodothyronine; T4 = thyroxine; THR = thyroid hormone receptor; UCP = mitochondrial uncoupling proteins.