Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPARα signaling.
Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPARα signaling.
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DOI：
10.1194/jlr.m031716
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发表时间：
2013-02
影响因子：
6.5
通讯作者：
Kratky D
中科院分区：
文献类型：
--
作者：
Obrowsky S;Chandak PG;Patankar JV;Povoden S;Schlager S;Kershaw EE;Bogner-Strauss JG;Hoefler G;Levak-Frank S;Kratky D
脂肪甘油三酯脂肪酶（ATGL）是介导甘油三酯（TG）水解的限速酶。ATGL的缺乏导致TG在多种组织中积累，强调了ATGL在维持脂质稳态中的关键作用。最近的证据表明，ATGL通过激活过氧化物酶体增殖物激活受体α（PPARα）影响TG代谢。为了研究肠ATGL对脂质代谢的特定作用，我们产生了仅在肠中缺乏ATGL的小鼠（ATGLiKO）。我们发现ATGLiKO小肠中TG水解酶活性降低，细胞内TG含量增加。[3H]三油酸酯的胃内给药导致放射性TG在肠道中的蓄积，而体循环的吸收没有变化。腹膜内注射的[3H]油酸酯也在ATGLiKO肠中的TG内积累，表明ATGL从体循环中动员脂肪酸，由基底侧从血液中吸收。PPARα靶基因的下调表明肠ATGL调节胆固醇吸收。因此，肠内ATGL缺乏导致胆固醇吸收延迟。重要的是，这项研究提供了证据表明，ATGL对肠道TG吸收没有影响，但水解了从肠腔和体循环中摄取的TG。我们的数据支持ATGL在调节小肠中的PPARα依赖性过程中的作用。
Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triglyceride (TG) hydrolysis. The lack of ATGL results in TG accumulation in multiple tissues, underscoring the critical role of ATGL in maintaining lipid homeostasis. Recent evidence suggests that ATGL affects TG metabolism via activation of peroxisome proliferator-activated receptor α (PPARα). To investigate specific effects of intestinal ATGL on lipid metabolism we generated mice lacking ATGL exclusively in the intestine (ATGLiKO). We found decreased TG hydrolase activity and increased intracellular TG content in ATGLiKO small intestines. Intragastric administration of [3H]trioleate resulted in the accumulation of radioactive TG in the intestine, whereas absorption into the systemic circulation was unchanged. Intraperitoneally injected [3H]oleate also accumulated within TG in ATGLiKO intestines, indicating that ATGL mobilizes fatty acids from the systemic circulation absorbed by the basolateral side from the blood. Down-regulation of PPARα target genes suggested modulation of cholesterol absorption by intestinal ATGL. Accordingly, ATGL deficiency in the intestine resulted in delayed cholesterol absorption. Importantly, this study provides evidence that ATGL has no impact on intestinal TG absorption but hydrolyzes TGs taken up from the intestinal lumen and systemic circulation. Our data support the role of ATGL in modulating PPARα-dependent processes also in the small intestine.