Ethanol Extract from Ulva prolifera Prevents High-Fat Diet-Induced Insulin Resistance, Oxidative Stress, and Inflammation Response in Mice

Abstract

Ulva prolifera is the major causative species in the green tide, a serious marine ecological disaster, which bloomed in the Yellow Sea and the Bohai Sea of China. However, it is also a popular edible seaweed and its extracts exerts anti-inflammatory and antioxidant effects. The present study investigated the effects of ethanol extract of U. prolifera (EUP) on insulin sensitivity, inflammatory response, and oxidative stress in high-fat-diet- (HFD-) treated mice. HFD-treated mice obtained drinking water containing 2% or 5% EUP. The results showed that EUP supplementation significantly prevented HFD-induced weight gain of liver and fat. EUP supplementation also improved glucose tolerance and insulin resistance in HFD-treated mice. Moreover, EUP supplementation prevented the increased expression of genes involved in triglyceride synthesis and proinflammatory genes and the decreased expression of genes involved in fatty acid oxidation in liver of HFD-treated mice. Furthermore, EUP supplementation decreased reactive oxygen species content, while increasing glutathione content and glutathione peroxidase activity in HFD-treated mice. In conclusion, our results showed that EUP improved insulin resistance and had antilipid accumulation and anti-inflammatory and antioxidative effects on HFD-treated mice. We suggested that U. prolifera extracts may be regarded as potential candidate for the prevention of nonalcoholic fatty liver disease.

Figure 1

Ethanol extract from U. prolifera prevented body weight gain in HFD-treated mice. CON, mice were fed on a low-fat diet; HF, mice were fed on a high-fat diet; LUP, mice were fed on a high-fat diet supplemented with 2% ethanol extract from U. prolifera; HUP, mice were fed on a high-fat diet supplemented with 5% ethanol extract from U. prolifera. Values are expressed as mean ± SEM, n = 8; ^∗p < 0.05; ∗ means significant difference between HF group and the other three groups.

Figure 2

Ethanol extract from U. prolifera improved glucose tolerance and insulin sensitivity in HFD-treated mice. (a) Serum insulin concentration. (b) Serum TG concentration. (c) Glucose tolerance test. (d) Insulin tolerance test. CON, mice were fed on a low-fat diet; HF, mice were fed on a high-fat diet; LUP, mice were fed on a high-fat diet supplemented with 2% ethanol extract from U. prolifera; HUP, mice were fed on a high-fat diet supplemented with 5% ethanol extract from U. prolifera. TG, triglyceride. Values are expressed as mean ± SEM, n = 8; ^∗p < 0.05; ∗ means significant difference between HF group and the other three groups.

Figure 3

Ethanol extract from U. prolifera prevented inflammatory response in liver of HFD-treated mice. CON, mice were fed on a low-fat diet; HF, mice were fed on a high-fat diet; LUP, mice were fed on a high-fat diet supplemented with 2% ethanol extract from U. prolifera; HUP, mice were fed on a high-fat diet supplemented with 5% ethanol extract from U. prolifera. Values are expressed as mean ± SEM, n = 8; ^∗p < 0.05; ∗ means significant difference between HF group and the other three groups.

Figure 4

Ethanol extract from U. prolifera improved oxidative stress in liver of HFD-treated mice. (a) ROS stained with dihydroethidium in liver (red). (b) Relative ROS content; (c) GSH content in liver; (d) GSH-Px activity in liver. CON, mice were fed on a low-fat diet; HF, mice were fed on a high-fat diet; LUP, mice were fed on a high-fat diet supplemented with 2% ethanol extract from U. prolifera; HUP, mice were fed on a high-fat diet supplemented with 5% ethanol extract from U. prolifera. ROS, reactive oxygen species; GSH, glutathione; GSH-Px, glutathione peroxidase. Values are expressed as mean ± SEM, n = 8; ^∗p < 0.05; ∗ means significant difference between HF group and the other three groups.

Figure 5

Ethanol extract from U. prolifera prevented lipid accumulation in liver of HFD-treated mice. CON, mice were fed on a low-fat diet; HF, mice were fed on a high-fat diet; LUP, mice were fed on a high-fat diet supplemented with 2% ethanol extract from U. prolifera; HUP, mice were fed on a high-fat diet supplemented with 5% ethanol extract from U. prolifera. DGAT, diacylglycerol O-acyltransferase; CPT-1a, carnitine palmitoyltransferase 1a; Acadm, medium-chain acyl-CoA dehydrogenase; ACOX1, acyl-CoA oxidase 1. Values are expressed as mean ± SEM, n = 8; ^∗p < 0.05; ∗ means significant difference between HF group and the other three groups.