Metabolomics reveals that vine tea (Ampelopsis grossedentata) prevents high-fat-diet-induced metabolism disorder by improving glucose homeostasis in rats

Abstract

Background: Vine tea (VT), derived from Ampelopsis grossedentata (Hand.-Mazz.) W.T. Wang, is an alternative tea that has been consumed widely in south China for hundreds of years. It has been shown that drinking VT on a daily basis improves hyperlipidemia and hyperglycemia. However, little is known about the preventive functions of VT for metabolic dysregulation and the potential pathological mechanisms involved. This paper elucidates the preventive effects of VT on the dysregulation of lipid and glucose metabolism using rats maintained on a high-fat-diet (HFD) in an attempt to explain the potential mechanisms involved.

Methods: Sprague Dawley (SD) rats were divided into five groups: a group given normal rat chow and water (control group); a group given an HFD and water (HFD group); a group given an HFD and Pioglitazone (PIO group), 5 mg /kg; and groups given an HFD and one of two doses of VT: 500 mg/L or 2000 mg/L. After 8 weeks, changes in food intake, tea consumption, body weight, serum and hepatic biochemical parameters were determined. Moreover, liver samples were isolated for pathology histology and liquid chromatography-mass spectrometry (LC-MS)-based metabolomic research.

Results: VT reduced the serum levels of glucose and total cholesterol, decreased glucose area under the curve in the insulin tolerance test and visibly impaired hepatic lipid accumulation. Metabolomics showed that VT treatment modulated the contents of metabolic intermediates linked to glucose metabolism (including gluconeogenesis and glycolysis), the TCA cycle, purine metabolism and amino acid metabolism.

Conclusion: The current results demonstrate that VT may prevent metabolic impairments induced by the consumption of an HFD. These effects may be caused by improved energy-related metabolism (including gluconeogenesis, glycolysis and TCA cycle), purine metabolism and amino acid metabolism, and reduced lipid levels in the HFD-fed rats.

Fig 1. Effect of vine tea (VT) and pioglitazone (PIO) on serum glucose and lipid profiles in rats.

At the end of 8 weeks, TC (A), TG (B), fasting blood glucose (C) and insulin (D) were measured. The calculated insulin sensitivity index (E) and HOMA-IR index (F) are displayed. ITT: Blood samples were collected from tail veins for glucose measurement at 0, 30, 60, 90 and 120 min after insulin injection (ii) (G). The calculated AUC is depicted (H). Data are presented as the means ± SEM. *P<0.05, **P<0.01, ***P<0.001 compared to normal control; #P<0.05, ##P<0.01, ###P<0.001 compared to the HFD model group, n = 8.

Fig 2. Vine tea (VT) improved hepatic lipid profiles and histopathological assessment in rats.

The liver sections were stained with H&E (magnification of 40). Control group (rats receiving only a common chow) (A); High fat-diet (HFD) group (rats receiving only an HFD) (B); PIO group (pioglitazone, 5 mg/kg, and an HFD) (C); 500 mg/L VT group (VT, 500 mg/L, and an HFD) (D); 2000 mg/L VT group (VT, 2000 mg/L, and HFD) (E). The liver tissues were subjected to lipid extraction for the measurement of TG (F) and TC (G). Data are presented as the means ± SEM. *P<0.05, **P<0.01, ***P<0.001 compared to normal control; #P<0.05, ##P<0.01, ###P<0.001 compared to HFD group, n = 8.

Fig 3. Vine tea (VT) regulated the disturbed metabolism induced by a high fat-diet (HFD) in rats.

Partial least-squares discriminant analysis (PLS-DA) score plots for HPLC/MS data of all the groups (A). PLS-DA score plots showed differences in the metabolic state in the control group (Con, Δ), the HFD model group (M, ◇), the pioglitazone groups (PIO,▽), the 2000 mg/L VT group (HIGH, +), and the 500 mg/L VT groups (LOW, ×). PLS-DA score plot showing the difference in the metabolic state between the control group (Con, Δ) and the HFD model group (M, +) (B). PLS-DA score plot showing the difference in the metabolic state between the HFD model group (M, Δ) and the PIO group (PIO, +) (C). PLS-DA score plot showing the difference in the metabolic state between the 500 mg/L VT groups (LOW, Δ) and the HFD model group (M, +) (D). PLS-DA score plot showing the difference in the metabolic state between the 2000 mg/L VT group (HIGH, Δ) and the HFD model group (M, +) (E). Summary of pathway analysis with MetPA (F). n = 6.

Fig 4. Metabolome pathway map of the quantified metabolites, including the components of glycolysis and the Krebs cycle in each group.

Black bar: control group (rats receiving only common chow); white bar: high fat-diet (HFD) group (rats receiving only an HFD); gray bar: vine tea (VT) group (VT, 2000 mg/L, and HFD). Data are presented as the means ± SEM. *P<0.05, **P<0.01 compared to normal control; #P<0.05, ##P<0.01 compared to HFD model group, n = 6.

Fig 5. Metabolome pathway map of purine metabolism and pyrimidine metabolism in each group.

Black bar: control group (rats receiving only a common chow); white bar: high fat-diet (HFD) group (rats receiving only an HFD); gray bar: vine tea (VT) group (VT, 2000 mg/L, and HFD). Data are presented as the means ± SEM. *P<0.05, **P<0.01, ***P<0.001 compared to normal control; #P<0.05, ##P<0.01, ###P<0.001 compared to HFD model group, n = 6.