Table 2.
Blueberries hepatoprotective effects in (pre)diabetic animal models.
| Animal Model | Source/Dose | Duration | Main Outcomes | Ref |
|---|---|---|---|---|
| HFD-fed male C57BL/6J mice | BB anthocyanin extract (200 mg/kg BW) |
8 weeks | ↓ BW, liver and adipose tissue weight ↓ Insulin levels ↓ HOMA-IR ↓ TGs and T-Chol ↓ Hepatic steatosis ↓ Serum ceramide and DAG levels ↓ Serum PP2A and Prkcz mRNA expression ↓ ALT and AST activities |
[32] |
| Obese Zucker rats | Freeze-dried wild BB powder (8% of diet) | 8 weeks | = BW ↓ Fasting plasma TAG and T-Chol ↓ Hepatic SREBP-1 and FAS mRNA expression = Hepatic PPAR-α and PPAR-γ mRNA expression |
[126] |
| ↓ Fasting plasma TNF- α, IL-6, and CRP ↑ Plasma adiponectin ↓ Hepatic TNF- α, IL-6, CRP and NF-kB mRNA expression |
[153] | |||
| HFD-fed Sprague Dawley rat | BB juice (15 g/kg) combined with probiotics | 8 weeks | ↓ Serum TGs, T-Chol, LDL-c and MDA ↓ Hepatic lipid accumulation ↑ Hepatic SIRT1and PPAR-α mRNA and protein expression ↓ Hepatic mRNA levels of SREBP-1c ↑ Serum SOD and GSH activities ↓ Serum ALT and AST activities |
[151] |
| ↑ Hepatic mitochondrial swelling ↓ State 3 and 4 respiration rates ↑ RCR and ADP/O ratio ↑ Hepatic mitochondrial GSH and SOD mRNA and protein expression levels ↑ Hepatic protein and mRNA expression of SIRT1 ↑ Hepatic mRNA expression of PGC-1α ↓ Hepatic mitochondrial MDA levels and ROS activity |
[146] | |||
| HFD-fed obese postmenopausal female C57BL/6J mice | BB powder (4% of diet) | 12 weeks | = BW and fat mass ↑ Glucose tolerance ↓ Hepatic steatosis ↑ Hepatic FAO and lipid handling (↑ LCHAD, and FAT/CD36 mRNA expression) ↑ Fecal SCFAs levels |
[154] |
| HFD-fed C57BL/6J mice | BB polyphenol extract (200 mg/kg body weight (bw)/day) |
12 weeks | ↓ BW ↓ Serum LDL -c levels ↑ Serum HDL-c levels ↓ Hepatic TGS and T-Chol ↓ Hepatic PPAR-γ, FAS, and SREBP-1 mRNA expression ↑ Hepatic CPT1 and PPAR-α mRNA expression ↑ AMPK phosphorylation |
[34] |
| HFD-fed male C57BL/6J mice | BB anthocyanins (200 mg/kg) |
12 weeks | ↓ BW ↓ Serum and hepatic lipid and MDA levels ↑ Hepatic SOD and GPx activities ↓ TNF-α, IL-6 and NF-kB mRNA expression ↑ Fecal SCFAS Hepatic glycerophospholipids and glutathione metabolism and insulin-signaling pathways modulation |
[155] |
| Diabetic male KK-Ay mice | BB anthocyanin extract (10 g/Kg diet) | 4 weeks | = BW and ↓ liver weight ↓ Serum glucose levels ↑ Insulin sensitivity ↓ Serum TGs and TC-Chol ↓ HGP ↑ Hepatic AMPK phosphorylation ↓ Hepatic lipid content ↓ Hepatic gluconeogenesis (↓ PEPCK and G6Pase mRNA expression) ↑ FAO (↑ PPAR-α, ACO and CPT1 mRNA expression) |
[136] |
| HFD-fed C57BL/6J mice | Fermented BB juice | 17 weeks | ↑ BW gain ↑ Insulin sensitivity and glucose homeostasis ↓ Fasting serum glucose ↓ Serum LDL-c ↓ Serum TNF-α and ↑ IL-10 ↓ Hepatic fat accumulation ↑ Hepatic mRNA expression of IR and IRS ↓ Hepatic SCD1, SREBP1c and FAS expression ↑ mRNA and protein expression of GLUT-1; GCK, LDL-receptor and PPAR-α ↓ mRNA and protein expression of PPAR-γ ↑ Akt phosphorylation |
[156] |
| GK rats | Decoctions of Vaccinium myrtillus L. (bilberry) leaves | 4 weeks | = BW ↑ Glucose tolerance ↓ Occasional glycaemia ↑ Mitochondrial oxidative and phosphorylative activities ↑ State 3 respiration, FCCP-uncoupled respiratory and RCR activities |
[149] |
ACO, acyl-CoA oxidase; Akt, protein kinase B; ALT, alanine aminotransferase; AMPK, 5′ adenosine monophosphate-activated protein kinase; AST, aspartate aminotransferase; BW, body weight; CPT1, carnitinepalmitoyltransferase-1A; DAG, diacylglycerol; FAO, fatty acid oxidation; FAS, fatty acid synthase; FCCP, carbonyl cyanide p-(tri-fluromethoxy)phenyl-hydrazone; G6Pase, glucose 6-phosphatase; GCK, Glucokinase; GLUT-1, glucose transporter 1; GPx, glutathione peroxidase; GK, Goto-Kakizaki; HGP, hepatic glucose production; HFD, high-fat diet; HOMA-IR, homeostatic model assessment for insulin resistance; IL, interleukin; LCHAD, long-chain hydroxyacyl-CoA dehydrogenase; LDL-c, low-density lipoprotein-cholesterol; MDA, malondialdehyde; PEPCK, phosphoenolpyruvate carboxykinase; RCR, respiratory control ratio; SCD1, stearoyl-CoA desaturase-1; SCFAS, short-chain fatty acids; SOD, superoxide dismutase; SREBP-1, sterol regulatory element-binding protein-1; TNF-α, tumor necrosis factor-α; T-Chol, total-cholesterol; ↑, increased; ↓, decreased; =, unchanged.