Eicosapentaenoic acid-enriched phospholipid ameliorates insulin resistance and lipid metabolism in diet-induced-obese mice

Abstract

Background: Over the past two decades, a striking increase in the number of people with metabolic syndrome (MS) has taken place worldwide. With the elevated risk of not only diabetes but also cardiovascular morbidity and mortality, there is urgent need for strategies to prevent this emerging global epidemic. The present study was undertaken to investigate the effects of dietary eicosapentaenoic acid-enriched phospholipid (EPA-PL) on metabolic disorders.

Methods: Male C57BL/6J mice (n = 7) were fed one of the following 4 diets for a period of 4 weeks: 1) a modified AIN-96G diet with 5% corn oil (control diet); 2) a high fat (20%, wt/wt) and high fructose (20%, wt/wt) diet (HF diet); 3) the HF diet containing 1% SOY-PL (SOY-PL diet); 4) the HF diet containing 1% EPA-PL (EPA-PL diet). The oral glucose tolerance test was performed. Plasma TG, TC, glucose, NEFA, insulin, leptin, adiponectin, TNF-α and IL-6 levels were assessed. In addition, hepatic lipid levels, lipogenic, and lipidolytic enzyme activities and gene expressions were evaluated.

Results: Both EPA-PL and SOY-PL significantly inhibited body weight gain and white adipose tissue accumulation, alleviated glucose intolerance, and lowered both serum fasting glucose and NEFA levels substantially. Only EPA-PL significantly reduced serum TNF-α and IL-6 levels, and increased serum adiponectin level. EPA-PL was more effective in reducing hepatic and serum TG and TC levels than SOY-PL. Both EPA-PL and SOY-PL reduced the activities of hepatic lipogenic enzymes, such as FAS and G6PDH, but only EPA-PL significantly increased CPT, peroxisomal β-oxidation enzymes activities and CPT-1a mRNA level. Alterations of hepatic lipogenic gene expressions, such as FAS, G6PDH, ACC, SCD-1 and SREBP-1c were consistent with changes in related enzyme activities.

Conclusions: According to our study, EPA-PL supplementation was efficacious in suppressing body fat accumulation, and alleviating insulin resistance and hepatic steatosis by modulating the secretion of adipocytokines and inflammatory cytokines, suppression of SREBP-1c mediated lipogenesis and enhancement of fatty acid β-oxidation. These results demonstrate that EPA-PL is a novel beneficial food component for the prevention and improvement of metabolic disorders.

Figure 1

Glucose tolerance test (A) and Area under curve (B) of C57BL/6J mice fed experimental diets^a.Note:^a Data are presented as mean ± SEM; n = 7 mice per group. ^#P < 0.05, ^##P < 0.05, significant difference compared to the control group determined by Student’s t test. ^*P < 0.05, significant difference compared to the HF group determined by ANOVA (Tukey’s test).

Figure 2

Hepatic enzyme activities involved in fatty acid biosynthesis in C57BL/6J mice fed experimental diets^a.Note:^a Data are presented as mean ± SEM; n = 7 mice per group. ^#P < 0.05, significant difference compared to the control group determined by Student’s t test. ^*P < 0.05, ^**P < 0.01, significant difference compared to the HF group determined by ANOVA (Tukey’s test).

Figure 3

Hepatic enzyme activities involved in fatty acid oxidation in C57BL/6J mice fed experimental diets^a.Note:^a Data are presented as mean ± SEM; n = 7 mice per group. ^##P < 0.01, significant difference compared to the control group determined by Student’s t test. ^**P < 0.01, significant difference compared to the HF group determined by ANOVA (Tukey’s test).

Figure 4

Hepatic mRNA expressions of genes related to lipid metabolism in C57BL/6J mice fed experimental diets^a.Note:^a Data are presented as mean ± SEM; n = 7 mice per group. ^#P < 0.05, significant difference compared to the control group determined by Student’s t test. ^*P < 0.05, ^**P < 0.01, significant difference compared to the HF group determined by ANOVA (Tukey’s test).