ORIGINAL ARTICLE Dietary Linoleic Acid Elevates the Endocannabinoids 2-AG and Anandamide and Promotes Weight Gain in Mice Fed a Low Fat Diet

The Author(s) 2013. This article is published with open access at Springerlink.com Abstract Dietary intake of linoleic acid (LNA, 18:2n-6) has increased dramatically during the 20th century and is associated with greater prevalence of obesity. The endo-cannabinoid system is involved in regulation of energy bal-ance and a sustained hyperactivity of the endocannabinoid system may contribute to obesity. Arachidonic acid (ARA, 20:4n-6) is the precursor for 2-AG and anandamide (AEA), and we sought to determine if low fat diets (LFD) could be made obesogenic by increasing the endocannabinoid pre-cursor pool of ARA, causing excessive endocannabinoid signaling leading to weight gain and a metabolic profile associated with obesity. Mice (C57BL/6j, 6 weeks of age) were fed 1 en % LNA and 8 en % LNA in low fat (12.5 en%) and medium fat diets (MFD, 35 en%) for 16 weeks. We found that increasing dietary LNA from 1 to 8 en % in LFD and MFD significantly increased ARA in phospholipids (ARA–PL), elevated 2-AG and AEA in liver, elevated plasma leptin, and resulted in larger adipocytes and more macrophage infiltration in adipose tissue. In LFD, dietary LNA of 8 en % increased feed efficiency and caused greater weight gain than in an isocaloric reduction to 1 en % LNA. Increasing dietary LNA from 1 to 8 en % elevates liver endocannabinoid levels and increases the risk of developing obesity. Thus a high dietary content of LNA (8 en%) increases the adipogenic properties of a low fat diet