Intestinal Cgi-58 deficiency reduces postprandial lipid absorption.
Intestinal Cgi-58 deficiency reduces postprandial lipid absorption.
复制标题
DOI：
10.1371/journal.pone.0091652
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yu L
中科院分区：
文献类型：
--
作者：
Xie P;Guo F;Ma Y;Zhu H;Wang F;Xue B;Shi H;Yang J;Yu L
比较基因鉴定-58 （CGI-58）是一种脂滴（LD）相关蛋白，在体外促进细胞内甘油三酯（TG）水解。人类CGI-58的突变导致TG在包括肠在内的许多组织中积累。肠细胞被认为不储存富含tg的ld，但脂肪膳食确实会诱导ld在细胞质内的暂时积累。积累的ld最终被清除，这意味着肠细胞中存在TG水解机制。然而，负责LD-TG水解的蛋白质的身份仍然未知。在这里，我们报告了小鼠肠道特异性CGI-58失活显著降低餐后血浆TG浓度和肠道TG水解酶活性，这与肠道TG含量增加4倍和吸收性肠细胞中大量细胞内LD积累有关。肠道特异性CGI-58基因敲除小鼠的肠道脂肪酸吸收和氧化也表现出轻微但显著的减少。令人惊讶的是，肠道CGI-58的失活显著提高血浆和肠道胆固醇，并降低肝脏胆固醇，而不改变肠道胆固醇吸收和粪便中性胆固醇排泄。综上所述，肠道CGI-58是有效的餐后脂蛋白- tg分泌和维持肝脏和血浆脂质稳态所必需的。我们的动物模型将作为一个有价值的工具，进一步确定肠道脂肪代谢如何影响代谢紊乱的发病机制，如肥胖和2型糖尿病。
Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes.
登录
查看更多内容
影响因子：
9.8
作者：
Lefevre, C;Jobard, F;Fischer, J
通讯作者：
Fischer, J
影响因子：
6.5
作者：
Brown, J. Mark;Betters, Jenna L.;Yu, Liqing
通讯作者：
Yu, Liqing
影响因子：
6.5
作者：
Brown, J. Mark;Chung, Soonkyu;Yu, Liqing
通讯作者：
Yu, Liqing
影响因子：
24.5
作者：
Robertson, MD;Parkes, M;Frayn, KN
通讯作者：
Frayn, KN
影响因子：
4.8
作者：
Subramanian, V;Rothenberg, A;Brasaemle, DL
通讯作者：
Brasaemle, DL