Dietary linoleic acid elevates endogenous 2-AG and anandamide and induces obesity.
Dietary linoleic acid elevates endogenous 2-AG and anandamide and induces obesity.
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DOI：
10.1038/oby.2012.38
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发表时间：
2012-10
期刊：
影响因子：
6.9
通讯作者：
Hibbeln, Joseph R.
中科院分区：
文献类型：
--
作者：
Alvheim, Anita R.;Malde, Marian K.;Osei-Hyiaman, Douglas;Lin, Yu Hong;Pawlosky, Robert J.;Madsen, Lise;Kristiansen, Karsten;Froyland, Livar;Hibbeln, Joseph R.
抑制过度活跃的内源性大麻素是减少肥胖的关键目标。内源性大麻素2-花生四烯酰甘油（2-AG）和花生四烯酰胺（AEA）的骨架都是ω-6脂肪酸花生四烯酸（AA）。在这里，我们假设，过量的饮食摄入亚油酸（LA），AA的前体，会诱导内源性大麻素过度活跃，促进肥胖。LA被分离为自变量，以反映世纪美国发生的LA从能量的1%（en%）增加到8 en%的饮食增加。从断奶开始，给小鼠喂食含有1 en% LA、8 en% LA和8 en% LA + 1 en%二十碳五烯酸（EPA）+二十二碳六烯酸（DHA）的中脂肪饮食（35 en%脂肪）和高脂肪饮食（60 en%）的饮食14周。将LA从1 en%增加到8 en%可升高肝脏和红细胞中的AA-磷脂（PL），使2-AG + 1-AG和AEA增加三倍，并与小鼠的摄食量、饲料效率和肥胖相关。通过向8en% LA饮食中添加1 en%长链ω-3脂肪来减少AA-PL导致类似于1 en% LA饮食的代谢模式。选择性地将LA降低至1 en%逆转了60 en%脂肪饮食的致肥胖特性。这些动物饮食模拟了世纪人类LA消耗的增加，这些变化与肥胖症患病率的增加密切相关。总之，饮食LA增加组织AA，随后升高2-AG + 1-AG和AEA，导致饮食诱导的肥胖的发展。LA的成脂作用可以通过消耗足够的EPA和DHA来减少AA-PL池并使内源性大麻素水平正常化来预防。
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 ω-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. LA 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 United States during the 20th 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 (PL) in liver and erythrocytes, tripled 2-AG + 1-AG and AEA associated with increased food intake, feed efficiency, and adiposity in mice. Reducing AA-PL by adding 1 en% long-chain ω-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 20th 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-PL pool and normalize endocannabinoid tone.
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影响因子：
120.7
作者：
Flegal, KM;Carroll, MD;Johnson, CL
通讯作者：
Johnson, CL
DOI：
10.1073/pnas.101119098
发表时间：
2001-05-22
影响因子：
11.1
作者：
Berger, A;Crozier, G;Di Marzo, V
通讯作者：
Di Marzo, V
影响因子：
15.9
作者：
Osei-Hyiaman, D;DePetrillo, M;Kunos, G
通讯作者：
Kunos, G
影响因子：
4.1
作者：
Matias, Isabel;Petrosino, Stefania;Di Marzo, Vincenzo
通讯作者：
Di Marzo, Vincenzo
影响因子：
4.8
作者：
Madsen, Lise;Pedersen, Lone Moller;Kristiansen, Karsten
通讯作者：
Kristiansen, Karsten