Global deletion of MGL in mice delays lipid absorption and alters energy homeostasis and diet-induced obesity
Global deletion of MGL in mice delays lipid absorption and alters energy homeostasis and diet-induced obesity
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DOI：
10.1194/jlr.m058586
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发表时间：
2015-06-01
影响因子：
6.5
通讯作者：
Storch, Judith
中科院分区：
文献类型：
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作者：
Douglass, John D.;Zhou, Yin Xiu;Storch, Judith
单酰基甘油脂肪酶（MGL）是一种广泛表达的酶，其催化单酰基甘油（MG）水解以产生FFA和甘油。MGL通过动员脂肪储存以及降解内源性大麻素2-花生四烯酸甘油来促进能量稳态。为了进一步研究MG代谢在能量稳态中的作用，MGL（-/-）小鼠被喂食10%（千卡）低脂饮食（LFD）或45%（千卡）高脂饮食（HFD）12周。与WT对照组小鼠相比，MGL（-/-）小鼠中MG种类显著增加。在基线和LFD喂养12周后，MGL（-/-）小鼠比WT小鼠瘦。HFD喂养的MGL（-/-）小鼠的循环脂质降低，参与葡萄糖稳态和能量平衡的几种血浆肽的水平也降低。有趣的是，MGL（-/-）小鼠在口服脂肪攻击后肠道TG分泌显著减少，表明脂质吸收延迟。总体而言，结果表明，整体MGL缺失导致全身变化，产生更瘦的表型和改善的血清代谢谱。
Monoacylglycerol lipase (MGL) is a ubiquitously expressed enzyme that catalyzes the hydrolysis of monoacylglycerols (MGs) to yield FFAs and glycerol. MGL contributes to energy homeostasis through the mobilization of fat stores and also via the degradation of the endocannabinoid 2-arachidonoyl glycerol. To further examine the role of MG metabolism in energy homeostasis, MGL(-/-) mice were fed either a 10% (kilocalories) low-fat diet (LFD) or a 45% (kilocalories) high-fat diet (HFD) for 12 weeks. Profound increases of MG species in the MGL(-/-) mice compared with WT control mice were found. Weight gain over the 12 weeks was blunted in both diet groups. MGL(-/-) mice were leaner than WT mice at both baseline and after 12 weeks of LFD feeding. Circulating lipids were decreased in HFD-fed MGL(-/-) mice, as were the levels of several plasma peptides involved in glucose homeostasis and energy balance. Interestingly, MGL(-/-) mice had markedly reduced intestinal TG secretion following an oral fat challenge, suggesting delayed lipid absorption. Overall, the results indicate that global MGL deletion leads to systemic changes that produce a leaner phenotype and an improved serum metabolic profile.