Diabetes is commonly associated with liver
lipid metabolism disorders.
AMP-activated protein kinase (AMPK) has a key role in regulating lipid metabolism. Grape seed
procyanidin B2 (GSPB2), a natural
polyphenol polymer, ameliorates
mitochondrial dysfunction and inhibits oxidative stress or apoptosis via AMPK pathways. In the present study, the hypothesis that GSPB2 treatment may ameliorate liver
lipid metabolic disorders by activating AMPK and downstream pathways was tested in diabetic mice. Db/m mice were used as controls, and diabetic db/db mice were randomly divided into 2 groups for treatment: Vehicle and GSPB2 (30 mg/kg/day for 10 weeks). Animals were weighed every week. Fasting blood was collected prior to sacrifice to measure fasting
blood glucose (FBG),
triglycerides (TG) and total
cholesterol (TC). Hepatic TG and
free fatty acid (FFA) levels were analyzed. Hepatic sections were examined by light microscopy following
hematoxylin and
eosin staining. The expression of hepatic AMPK, phosphorylated acetyl‑CoA carboxylase (ACC),
carnitine palmitoyl
transferase 1 (CPT1) and 4‑hydroxynonenal (4‑HNE) was measured by western blot analysis. Liver mitochondria were isolated to assess
electron transport complex I (CI), complex II (CII) and complex IV by high-resolution respirometry. The results demonstrated that GSPB2 significantly decreased
body weight and serum TG, TC and FFA levels, but not FBG levels in diabetic mice. GSPB2 visibly decreased lipid droplet accumulation in the liver and significantly reduced hepatic TG and FFA levels. In diabetic mice, GSPB2 restored liver AMPK and ACC phosphorylation, increased CPT1
protein expression, ameliorated lipid peroxidation damage, which was assessed by comparing 4‑HNE levels, and partially restored the damaged mitochondrial respiratory capacity of CI and CII in the liver. In conclusion, long‑term oral treatment with GSPB2 may benefit hepatic
lipid metabolism disorders, potentially by decreasing hepatic
lipid synthesis and increasing hepatic FFA β‑oxidation via the AMPK‑ACC pathway.