Effects of resveratrol and other polyphenols in hepatic steatosis

Table 2 In vivo studies carried out with resveratrol

Ref.	Animal model	Resveratrol dose and treatment period length	Effects	Mechanisms
Baur et al[31], 2006	Male C57BL/6NIA mice fed a high-fat diet	0.04% in the diet (estimated 22.4 mg/kg bw per day)	↓ Lipid droplets in liver	↓ Acetylation status of PGC-1α protein in liver
		6 wk
		186 mg kg bw per day	↑ Mitochondrial number
		6 wk
Kasdallah-Grissa et al[39], 2006	Male Wistar rats fed a standard diet	0.04% in the diet (estimated 300-450 mg/kg bw per day)	↓ Oxidative stress
	3 g ethanol/kg bw per day	6 wk	↓ Lipid peroxidation
Ahn et al[32], 2008	Male C57BL6/J mice fed an atherogenic diet	0.0125% in the diet (estimated 10 mg/kg bw per day)	↓Total lipids and triacylglycerols in liver	↓ Expression lipogenic enzymes
		8 wk	Ameliorated necroinflammation	↑ Expression enzymes involved in fatty acid oxidation
				↑ SIRT1 mRNA expression
Ajmo et al[40], 2008	Male C57BL/6J mice fed a low-fat diet	200 mg/kg bw per day	↓ Liver weight	↓ SREBP-1c mRNA and protein expressions
	Ethanol added to account 29% of total calories	400 mg/kg bw per day 4 wk	↓ Lipid droplets	↓ FAS, SCD, ACC, ME mRNA
			↓ Triacylglycerols	↑ PGC-1α mRNA
				↑ ACO, CPT-1a mRNA
				↑ Fatty acid oxidation
				Activation AMPK/SIRT1 axis
Bujanda et al[37], 2008	Male Wistar rats	10 mg/kg bw per day	↓ Liver fat infiltration
	Steatosis induced by feeding rats ad libitum for four days per week and then fasting them the remaining three days	4 wk	↓ Oxidative stress ↓ ALT
Kim et al[33], 2008	C57BL/6J mice a high fat diet	0.4% in the diet (estimated 400 mg/kg bw per day) 10 wk	↓ Liver weight
			↓ Triacylglycerols
Shang et al[30], 2008	Male Wistar rats fed a high-fat, high-sucrose diet	100 mg/kg bw per day 10 wk	↓ Triacylglycerols	↑ AMPK phosphorylation (activation)
			↓ Lipid droplets	↓ SREBP-1c and FAS mRNA
Rivera et al[42], 2009	Male fa/fa Zucker rats fed standard diet	10 mg/kg bw per day 8 wk	↓ Triacylglycerols	↓ ACC activity
				AMPK activation
Cho et al[34], 2012	Male C57BL/6J mice fed a high-fat diet	0.005% in the diet (0.5 mg/kg bw per day)	0.5 mg/kg bw per day	↓ PAP = Enzymes involved in fatty acid oxidation
		10 wk	↓ Triacylglycerols
			↓ Number and size of liver fat droplets	↓ FAS and ME activities
		0.02% in the diet (2 mg/kg bw per day)	2 mg/kg bw per day ↓ Triacylglycerols	↓ PAP = Enzymes involved in fatty acid oxidation
		10 wk	↓ Number and size of liver fat droplets
Gómez-Zorita et al[43], 2012	Male fa/fa Zucker rats fed a standard diet	15 mg/kg bw per day	15 and 45 mg/kg bw	= Lipogenic enzyme activity
		45 mg/kg bw per day	↓ Liver weight	↑ Activity of enzymes involved in fatty acid oxidation
			↓ Triacylglycerols
		6 wk	↓ Oxidative stress
			15 mg/kg bw↓ Transaminases
Poulsen et al[35], 2012	Male Wistar rats fed a high-fat diet	100 mg/kg bw per day	Normalized triacylglycerols No hepatic inflammation	↑ UCP2 ↑ Mitochondria number
		8 wk
Alberdi et al[36], 2013	Male Sprague-Dawley rats fed a high-fat, high-sucrose diet	30 mg/kg of bw per day	↓ Triacylglycerols	↑ Activity of enzymes involved in fatty acid oxidation = FAS, G6PDH, ME activities
		6 wk
				↑ Phosphorylated ACC/total ACC (inhibition)
				↑ Phosphorylated AMPK/total AMPK (activation)
				= PPAR-α, SREBP-1c, SIRT1, PGC-1α, TFAM, COX2, and HNF-4α, ↓ Acetylated PGC-1α /total PGC-1α (activation)
Franco et al[38], 2013	Lactating Wistar rats	30 mg/kg per day	↓ Triacylglycerols
		4 wk	↓ Oxidative stress

↓: Decrease; ↑: Increase. BW: Body weight; PGC-1α: Peroxisome proliferator-activated receptor-c coactivator 1 α; SIRT1: Sirtuin 1; SREBP-1c: Sterol regulatory element binding protein 1c; FAS: Fatty acid synthase; SCD: Stearoylcoenzyme A desaturase; ACC: Acetyl CoA carboxylase; ME: Malic enzyme; ACO: Acyl-coenzyme A oxidase 1; CPT-1a: Carnitine palmitoyltransferase 1a; AMPK: AMP-activated kinase; ALT: Alanine aminotransferase; PPAR-γ: Peroxisome proliferator-activated receptor γ; C/EBP: CCAAT/enhancer binding protein; LXR: Liver X receptor; PAP: Phosphatidate phosphohydrolase; UCP2: Mitochondrial uncoupling protein 2; G6PDH: Glucose-6-phosphate dehydrogenase; PPAR-α: Peroxisome proliferator-activated receptor α; TFAM: Mitochondrial transcription factor A; COX2: Cyclooxygenase 2; HNF-4 α: Hepatocyte nuclear factor 4 α.