Over-expression of monoacylglycerol lipase (MGL) in small intestine alters endocannabinoid levels and whole body energy balance, resulting in obesity.
Over-expression of monoacylglycerol lipase (MGL) in small intestine alters endocannabinoid levels and whole body energy balance, resulting in obesity.
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DOI：
10.1371/journal.pone.0043962
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Storch J
中科院分区：
文献类型：
--
作者：
Chon SH;Douglass JD;Zhou YX;Malik N;Dixon JL;Brinker A;Quadro L;Storch J
小肠单酰基甘油脂肪酶（MGL）的功能尚不清楚。其在该组织中的表达是令人惊讶的，因为小肠的主要功能之一是将膳食来源的MG转化为三酰甘油（TG），而不是降解它们。为了阐明肠道MGL的功能，我们产生了在小肠中特异性过表达MGL的转基因小鼠（iMGL小鼠）。仅3周高脂肪喂养后，iMGL小鼠显示肥胖表型;与野生型同窝小鼠相比，iMGL小鼠的体重增加和体脂量显著更高，沿着肝脏和血浆TG水平升高。iMGL小鼠贪食，尽管瘦体重不变，但能量消耗减少，表明肥胖增加是由于热量摄入增加和全身效应导致代谢率降低。转基因的存在导致肠粘膜中大多数MG种类的水平较低，包括内源性大麻素2-花生四烯酸甘油（2-AG）。因此，结果表明肠道MGL和肠道2-AG以及可能的其他MG种类通过调节食物摄入以及代谢率在全身能量平衡中的作用。
The function of small intestinal monoacylglycerol lipase (MGL) is unknown. Its expression in this tissue is surprising because one of the primary functions of the small intestine is to convert diet-derived MGs to triacylglycerol (TG), and not to degrade them. To elucidate the function of intestinal MGL, we generated transgenic mice that over-express MGL specifically in small intestine (iMGL mice). After only 3 weeks of high fat feeding, iMGL mice showed an obese phenotype; body weight gain and body fat mass were markedly higher in iMGL mice, along with increased hepatic and plasma TG levels compared to wild type littermates. The iMGL mice were hyperphagic and displayed reduced energy expenditure despite unchanged lean body mass, suggesting that the increased adiposity was due to both increased caloric intake and systemic effects resulting in a hypometabolic rate. The presence of the transgene resulted in lower levels of most MG species in intestinal mucosa, including the endocannabinoid 2-arachidonoyl glycerol (2-AG). The results therefore suggest a role for intestinal MGL, and intestinal 2-AG and perhaps other MG species, in whole body energy balance via regulation of food intake as well as metabolic rate.
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影响因子：
7.7
作者：
Hajri, Tahar;Hall, Angela M.;Abumrad, Nada A.
通讯作者：
Abumrad, Nada A.
影响因子：
3.6
作者：
Dinh, TP;Kathuria, S;Piomelli, D
通讯作者：
Piomelli, D
DOI：
10.1073/pnas.1104675108
发表时间：
2011-08-02
影响因子：
11.1
作者：
DiPatrizio, Nicholas V.;Astarita, Giuseppe;Piomelli, Daniele
通讯作者：
Piomelli, Daniele
DOI：
10.1016/0005-2760(86)90286-9
发表时间：
1986-04-15
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FREDRIKSON, G;TORNQVIST, H;BELFRAGE, P
通讯作者：
BELFRAGE, P
DOI：
10.1152/ajpgi.90500.2008
发表时间：
2008-12-01
影响因子：
4.5
作者：
Duncan, Marnie;Thomas, Adam D.;Sharkey, Keith A.
通讯作者：
Sharkey, Keith A.