EPA Prevents Fat Mass Expansion and Metabolic Disturbances in Mice Fed With a Western Diet

J Lipid Res. 2016 Aug;57(8):1382-97. doi: 10.1194/jlr.M065458. Epub 2016 Jun 15.


The impact of alpha linolenic acid (ALA), EPA, and DHA on obesity and metabolic complications was studied in mice fed a high-fat, high-sucrose (HF) diet. HF diets were supplemented with ALA, EPA, or DHA (1% w/w) and given to C57BL/6J mice for 16 weeks and to Ob/Ob mice for 6 weeks. In C57BL/6J mice, EPA reduced plasma cholesterol (-20%), limited fat mass accumulation (-23%) and adipose cell hypertrophy (-50%), and reduced plasma leptin concentration (-60%) compared with HF-fed mice. Furthermore, mice supplemented with EPA exhibited a higher insulin sensitivity (+24%) and glucose tolerance (+20%) compared with HF-fed mice. Similar effects were observed in EPA-supplemented Ob/Ob mice, although fat mass accumulation was not prevented. By contrast, in comparison with HF-fed mice, DHA did not prevent fat mass accumulation, increased plasma leptin concentration (+128%) in C57BL/6J mice, and did not improve glucose homeostasis in C57BL/6J and Ob/Ob mice. In 3T3-L1 adipocytes, DHA stimulated leptin expression whereas EPA induced adiponectin expression, suggesting that improved leptin/adiponectin balance may contribute to the protective effect of EPA. In conclusion, supplementation with EPA, but not ALA and DHA, could preserve glucose homeostasis in an obesogenic environment and limit fat mass accumulation in the early stage of weight gain.

Keywords: adipose tissue; eicosapentaenoic acid; insulin resistance; obesity; omega-3 polyunsaturated fatty acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipogenesis
  • Adipokines / metabolism
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism
  • Adipose Tissue, White / pathology*
  • Adiposity / drug effects
  • Animals
  • Anti-Obesity Agents / pharmacology*
  • Cell Membrane / metabolism
  • Diet, Western / adverse effects*
  • Drug Evaluation, Preclinical
  • Eicosapentaenoic Acid / pharmacology*
  • Erythrocytes / metabolism
  • Gene Expression
  • Glucose Intolerance
  • Insulin Resistance
  • Leptin / genetics
  • Leptin / metabolism
  • Lipid Metabolism / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / drug therapy
  • Obesity / etiology
  • Obesity / metabolism*
  • Phospholipids / metabolism


  • Adipokines
  • Anti-Obesity Agents
  • Leptin
  • Phospholipids
  • Eicosapentaenoic Acid