(28-02-12) Dietary linoleic acid elevates endogenous 2-AG and anandamide and induces obesity.

Alvheim AR, Malde MK, Osei-Hyiaman D, Hong Lin Y, Pawlosky R, Madsen L, Kristiansen K, Fr?yland L, Hibbeln JR.
Source
1] National Institute of Nutrition and Seafood Research (NIFES), Bergen, Norway [2] National Institute on Alcohol Abuse & Alcoholism, NIH, Bethesda, Maryland, USA [3] Department of Biomedicine, University of Bergen, Norway.
Abstract
Suppressing hyperactive endocannabinoid tone is a critical target for reducing obesity. The backbone of both endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) is the omega-6 fatty acid arachidonic acid (AA). Here we posited that excessive dietary intake of linoleic acid (LA), the precursor of AA, would induce endocannabinoid hyperactivity and promote obesity. Linoleic acid was isolated as an independent variable to reflect the dietary increase in LA from 1 percent of energy (en%) to 8 en% occurring in the US during the 20(th) century. Mice were fed diets containing 1 en% LA, 8 en% LA and 8 en% LA + 1 en% eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) in medium fat diets (35 en% fat) and high fat diets (60 en%) for 14 weeks from weaning. Increasing LA from 1 en% to 8 en% elevated AA -phospholipids in liver and erythrocytes, tripled 2-AG+1-AG and AEA associated with increased food intake, feed efficiency and adiposity in mice. Reducing AA -phospholipids by adding 1en% long-chain omega-3 fats to 8 en% LA diets resulted in metabolic patterns resembling 1 en% LA diets. Selectively reducing LA to 1 en% reversed the obesogenic properties of a 60 en% fat diet. These animal diets modeled 20(th) century increases of human LA consumption, changes that closely correlate with increasing prevalence rates of obesity. In summary, dietary LA increased tissue AA, and subsequently elevated 2-AG+1-AG and AEA resulting in the development of diet-induced obesity. The adipogenic effect of LA can be prevented by consuming sufficient EPA and DHA to reduce the AA -phospholipid pool and normalize endocannabinoid tone.

Source: Obesity (Silver Spring). 2012 Feb

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