Grape seed procyanidin B2 ameliorates hepatic lipid metabolism disorders in db/db mice

Yin,Mei; Zhang,Pei; Yu,Fei; Zhang,Zhen; Cai,Qian; Lu,Weida; Li,Baoying; Qin,Weidong; Cheng,Mei; Wang,Hao; Gao,Haiqing

doi:10.3892/mmr.2017.6900

Grape seed procyanidin B2 ameliorates hepatic lipid metabolism disorders in db/db mice

Authors:
- Mei Yin
- Pei Zhang
- Fei Yu
- Zhen Zhang
- Qian Cai
- Weida Lu
- Baoying Li
- Weidong Qin
- Mei Cheng
- Hao Wang
- Haiqing Gao
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Affiliations: Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Endocrinology, Liaocheng People's Hospital Affiliated to Taishan Medical College, Liaocheng, Shandong 252000, P.R. China, Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: June 30, 2017 https://doi.org/10.3892/mmr.2017.6900
Pages: 2844-2850

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Abstract

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.

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