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

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.

The Preventative Effects of Procyanidin on Binge Ethanol‐Induced Lipid Accumulation and ROS Overproduction via the Promotion of Hepatic Autophagy

“…Procyanidins represent a group of naturally occurring plant polyphenols withpowerful antioxidative properties, and are mainly found in grape seeds, grape skin, and green tea. Several researches have demonstrated the beneficial effects of grape seeds procyanidins on metabolic diseases . Here, we study the anti‐ALD action of a dimer procyanidin (DPC, Figure ), which is composed of catechins linked by a C─O─C bond.…”

Growth Performance, Carcass Traits and Breast Meat Fatty Acids Profile of Helmeted Guinea Fowls (Numida meleagris) Fed Increasing Level of Linseed (Linum usitatissimum) and Pumpkin Seed (Cucurbita moschata) Meals

“…Currently, lipid metabolism disorders are considered a serious health problem in the world population, mainly causing obesity, insulin resistance, inflammation, coronary artery disease and type 2 diabetes (Cao, 2014). The main risk factors for these types of diseases are high body mass index, consumption of alcohol and tobacco, lack of physical activity, low fruit and vegetable intake, high saturated fat intake and low in essential fatty acids, and high n-6/n-3 ratio (Yin et al, 2017). In this sense, many international organizations have recommended the daily consumption of essential fatty acids omega 3 and omega 6, as well as a close ratio between them to stimulate brain development and decrease the induction of different types of cancer and metabolic diseases (British Nutrition Foundation, 1992;World Health Organization/FAO, 1995).…”

Achacha (Garcinia humilis) Rind Improves Cardiovascular Function in Rats with Diet-Induced Metabolic Syndrome

“…The treatment also reduced malondialdehyde concentrations and promoted antioxidant enzyme activities (catalase and superoxide dismutase) compared to the vehicle-treated group, which were related to the activation of Nrf2 protein that upregulates antioxidant defences [ 52 ]. Procyanidin B2 supplementation also reduced 4-hydroxynonenal which is a measure of lipid peroxidation by reactive oxygen species [ 53 ] and advanced glycation end products [ 54 ].…”

“…As in our study, no differences were shown in serum NEFA concentrations between high-fat and groups treated with epicatechin (10 mg/kg), catechin (10 mg/kg), or procyanidin B2 (10 mg/kg) except those treated with the combination as cocoa powder (100 mg/kg) [ 64 ]. However, administration of 30 mg/kg/day of grape seed procyanidin B2 in diabetic db / db mice reduced body weight [ 53 ].…”