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, 59 (10), 2495-504

Antiobesity Effect of Eicosapentaenoic Acid in High-Fat/High-Sucrose Diet-Induced Obesity: Importance of Hepatic Lipogenesis

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Antiobesity Effect of Eicosapentaenoic Acid in High-Fat/High-Sucrose Diet-Induced Obesity: Importance of Hepatic Lipogenesis

Ayumi Sato et al. Diabetes.

Abstract

Objective: Given the pleiotropic effect of eicosapentaenoic acid (EPA), it is interesting to know whether EPA is capable of improving obesity. Here we examined the anti-obesity effect of EPA in mice with two distinct models of obesity.

Research design and methods: Male C57BL/6J mice were fed a high-fat/high-sucrose diet (25.0% [w/w] fat, 32.5% [w/w] sucrose) (HF/HS group) or a high-fat diet (38.1% [w/w] fat, 8.5% [w/w] sucrose) (HF group) for 4-20 weeks. A total of 5% EPA was administered by partially substituting EPA for fat in the HF/HS + EPA and HF + EPA groups.

Results: Both the HF/HS and HF groups similarly developed obesity. EPA treatment strongly suppresses body weight gain and obesity-related hyperglycemia and hyperinsulinemia in HF/HS-fed mice (HF/HS + EPA group), where hepatic triglyceride content and lipogenic enzymes are increased. There is no appreciable effect of EPA on body weight in HF-fed mice (HF + EPA group) without enhanced expression of hepatic lipogenic enzymes. Moreover, EPA is capable of reducing hepatic triglyceride secretion and changing VLDL fatty acid composition in the HF/HS group. By indirect calorimetry analysis, we also found that EPA is capable of increasing energy consumption in the HF/HS + EPA group.

Conclusions: This study is the first demonstration that the anti-obesity effect of EPA in HF/HS-induced obesity is associated with the suppression of hepatic lipogenesis and steatosis. Because the metabolic syndrome is often associated with hepatic lipogenesis and steatosis, the data suggest that EPA is suited for treatment of the metabolic syndrome.

Figures

FIG. 1.
FIG. 1.
Effect of EPA on HF/HS- and HF-induced obesity. A and B: Body weight change. C and D: WAT weights. E and F: Proinflammatory gene expression in the epididymal WAT. n = 7–10. †P < 0.05; ††P < 0.01 vs. control group. **P < 0.01 vs. HF (/HS) group.
FIG. 2.
FIG. 2.
Effect of EPA on HF/HS- and HF-induced metabolic abnormalities. A and B: Plasma insulin. C and D: Plasma glucose. E and F: Hepatic triglyceride content. †P < 0.05; ††P < 0.01 vs. control group. *P < 0.05; **P < 0.01 vs. HF (/HS) group.
FIG. 3.
FIG. 3.
Effect of EPA on energy metabolism–related genes in the HF/HS groups. A and B: Liver. C and D: Skeletal muscle. E: Epididymal WAT. F: Hepatic SREBP-1 protein in the HF/HS group. n = 7–10. †P < 0.05; ††P < 0.01 vs. control group. *P < 0.05; **P < 0.01 vs. HF/HS group. ACO, acyl-CoA oxidase; ATGL, adipose triglyceride lipase; CPT-1a, carnitine palmitoyltransferase-1a; CS, citrate synthase; GK, glucokinase; HAD, hydroxyacyl-CoA dehydrogenase; HK-2, hexokinase-2; HSL, hormone-sensitive lipase; MCAD, acetyl-CoA dehydrogenase, medium chain; PFKL, phosphofructokinase, liver; PFKM, phosphofructokinase, muscle, B-type.
FIG. 4.
FIG. 4.
Effect of EPA on energy metabolism–related genes in the HF groups. A and B: Liver. C: Skeletal muscle. D: Epididymal WAT. E: Hepatic SREBP-1 protein in the HF group. n = 10. †P < 0.05; ††P < 0.01 vs. control group. **P < 0.01 vs. HF group. ACO, acyl-CoA oxidase.
FIG. 5.
FIG. 5.
Effect of EPA on triglyceride secretion rate (TGSR) and VLDL fatty acid composition in the HF/HS group. A: TGSR. B: VLDL fatty acid composition. n = 6. †P < 0.05; ††P < 0.01 vs. control group. *P < 0.05; **P < 0.01 vs. HF/HS group.
FIG. 6.
FIG. 6.
Effect of EPA on WAT lipolysis and energy consumption in the HS/HF group. A: Glycerol release from epididymal WAT with or without 10 μmol/l isoproterenol. B: UCP-1 mRNA expression in BAT. Indirect calorimetry analysis of VO2 (C and D) and RER (E and F). n = 9. ††P < 0.01 vs. control group. *P < 0.05; **P < 0.01 vs. HF/HS group.
FIG. 7.
FIG. 7.
Possible mechanism underlying the anti-obesity effect of EPA. EPA prevents WAT accumulation in HF/HS-induced obese mice possibly through the suppression of hepatic lipogenesis and enhancement of energy consumption.

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