Table 1.
Rodent resveratrol studies with histological liver data
| Ref. | Focus | Model | RSV dose | RSV exposure (wk) | Histology/LW | TG/CH content | Liver AMPK activation | Suggested RSV actions/mechanisms |
| Baur et al[37] (2006) | Longevity | Middle-aged DIO mice | 22.4 mg/kg BW = 0.04% in diet | 27 | +/+ | ND | + | Elevated PGC-1α deacetylation as marker of enzymatic SIRT1 activity. Phosphorylation of ACC |
| Ahn et al[65] (2008) | NAFLD/NASH | DIO mice (1% CH in diet) | 1.25 g/kg diet | 8 | +/+ Decrease in NASH | +/- | ND | Reduced hepatic expression of FAS, PPARγ, CD36. Increased PPARα expression |
| Kang et al[46] (2010) | Insulin signaling | DIO mice | 30 mg/kg BW | 2 | +/ND | ND | - | Increased Akt phosphorylation, improving insulin signaling |
| Labbé et al[109] (2011) | NAFLD, metabolic profile, longevity | Werner syndrome mice | 0.04% RSV in diet | Life-long (≤ 22.5 mo) | +/ND | ND | - | Decreased FAS expression Decreased HCC prevalence |
| Tauriainen et al[115] (2011) | Obesity, NAFLD | DIO mice | 2 or 4 g/kg diet | 15 | +/ND | ND | ND | Increased SIRT1 expression in liver tissue. High-dose most effective |
| Cho et al[111] (2012) | NAFLD | DIO mice (1% CH in diet) | 7 mg/kg BW or 30 mg/kg BW | 10 | +/ND | +/+ | ND | Suppressed FAS activity. Activation of FA β-oxidation in liver. The lower dose is more efficient than the higher dose |
| Zhou et al[108] (2012) | Overall transcriptomic and metabolic profiling | DIO mice | 0.04% or 0.02% RSV + quercetin 0.02% | 26 | +/ND | -/+ | ND | Modulation of inflammation and FA β-oxidation. Combination with quercetin was more effective than RSV alone |
| Jeon et al[51] (2012) | Cognitive deficit | DIO mice | 200 mg/kg BW | 20 | +/ND | ND | ND | Attenuation of hepatic lipid peroxidation and macrophage infiltration |
| Shiozaki et al[97] (2012) | Longevity | SAMP10 mice | 0.04% RSV | 20 | +/ND | ND | ND | Inhibition of ACC. Improved mitochon-drial number, redox status and activity |
| Gao et al[114] (2013) | NAFLD | T0901317-treated mice | 200 mg/kg BW | < 1 | +/+ | +/ND | + | Inhibition of ACC. Unchanged expression SREBP-1c and related genes |
| Li et al[110] (2013) | NAFLD | HFS mice | 50 mg/kg BW | 3 | +/ND Decrease in NASH | ND | ND | Inhibition of NF-κB-induced inflamma-tion and MDA-induced oxidative stress. Protection against NASH fibrosis |
| Bujanda et al[49] (2008) | NAFLD | Fasting/feeding special diet, rats | 10 mg daily | 4 | +/- | ND | ND | Hepatic TNF-α decrease. Improved oxidant/antioxidant markers (MDA, NOS, SOD, e.g., catalase) |
| Shang et al[74] (2008) | NAFLD | HFD rats | 100 mg/kg BW | 10 | +/+ | +/- | + | Suppressed SREBP-1c and FAS gene expression |
| Poulsen et al[76] (2012) | NAFLD | HFD rats | 100 mg daily | 8 | +/- | +/ND | - | Increased UCP2 expression Increased mitochondrial number |
| Gomez-Zorita et al[103] (2012) | NAFLD | Obese Zucker rats | 15 mg/kg BW or 45 mg/kg BW | 6 | +/+ | +/? | ND | Increased CPT-1α and ACO No effect on activity of lipogenic enzymes |
| Bagul et al[94] (2012) | Oxidative stress | High fructose fed rats | 10 mg/kg BW | 8 | +/ND | ND | ND | Attenuation of hepatic oxidative stress, e.g., with increased level of NRF2 |
| Franco et al[96] (2013) | Oxidative stress and NAFLD | Obese ‘early weaned’ rats | 30 mg/kg BW | 4 | +/ND | +/ND | ND | Decreased markers of oxidative stress |
| Xin et al[66] (2013) | NAFLD | HFS rats | 50 or 100 mg/kg BW | 13 | +/ND | +/+ | ND | Decreased hepatic LDLr and SRB1 mRNA and protein express |
| Cho et al[67] (2008) | Hyperlipidemia | HFD hamsters | 0.25 g/kg diet | 8 | +/+ | +/+ | ND | Decreased HMG-CoA expression and modulated lipoprotein expression |
| Burgess et al[110] (2011) | Metabolic syndrome | HFD mini-swine | 100 mg/kg daily | 11 | (+)/ND | ND | ND | Improved insulin sensitivity |
+ positive finding; - negative finding; ND: Not determined. LW: Liver weight; BW: Body weight; TG: Triglyceride; CH: Cholesterol; AMPK: AMP-activated protein kinase; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1 α; SIRT1: Silent information regulation 2 homolog 1; ACC: Acetyl-CoA carboxylase; NAFLD/NASH: Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis; DIO: Diet induced obesity; FAS: Fatty acid synthase; PPARγ/α: Peroxisome proliferator-activated receptor γ/α; SAMP10: Senescence-accelerated mouse P10; HCC: Hepatocellular carcinoma; FA: Fatty acids; SREBP-1c: Sterol regulatory element-binding protein-1c; TNF-α: Tumor necrosis factor-α; MDA: Malondialdehyde; NOS: Nitric oxide synthase; SOD: Superoxide dismutase; HFD: High fat diet; UCP2: Uncoupling protein 2; CPT-1α: Carnitine palmitoyl transferase-1α; ACO: Acyl-coenzyme A oxidase; NRF2: Nuclear factor-like 2; HFS: High fat/sucrose diet; LDLr: Low-density lipoprotein receptor; SRB1: Scavenger receptor class B member 1; HMG-CoA: 3-hydroxy-3-methylglutaryl-coenzyme A.