title: Antiobesity effect of eicosapentaenoic acid in high-fat/high-sucrose diet-induced obesity: importance of hepatic lipogenesis.
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.
  
  
  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.
authors.affiliation: Development Research, Pharmaceutical Research Center, Mochida Pharmaceutical, Shizuoka, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawano
authors.forename: Tatsuto
authors.initials: T
authors.lastname: Notsu
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ohta
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakakuki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Mizuguchi
authors.forename: Michiko
authors.initials: M
authors.lastname: Itoh
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suganami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000517:prevention & control; D004041:Dietary Fats / Q000494:pharmacology*; D019422:Dietary Sucrose / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D002149:Energy Intake; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005395:Fish Oils / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced / Q000517:prevention & control; D006946:Hyperinsulinism / Q000139:chemically induced / Q000517:prevention & control; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000517:prevention & control; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D001786:Blood Glucose; D004041:Dietary Fats; D019422:Dietary Sucrose; D005230:Fatty Acids, Nonesterified; D005395:Fish Oils; D007328:Insulin; D014280:Triglycerides; D002784:Cholesterol; D015118:Eicosapentaenoic Acid