ATGL/CGI-58-Dependent Hydrolysis of a Lipid Storage Pool in Murine Enterocytes

被引:31
作者
Korbelius, Melanie [1 ]
Vujic, Nemanja [1 ]
Sachdev, Vinay [1 ,3 ]
Obrowsky, Sascha [1 ,4 ]
Rainer, Silvia [1 ]
Gottschalk, Benjamin [1 ]
Graier, Wolfgang F. [1 ,2 ]
Kratky, Dagmar [1 ,2 ]
机构
[1] Med Univ Graz, Gottfried Schatz Res Ctr, Mol Biol & Biochem, A-8010 Graz, Austria
[2] BioTechMed Graz, A-8010 Graz, Styria, Austria
[3] Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 Amsterdam, Netherlands
[4] EVER Neuro Pharma, A-4866 Unterach Am Attersee, Upper Austria, Austria
基金
奥地利科学基金会;
关键词
ADIPOSE TRIGLYCERIDE LIPASE; FREE FATTY-ACIDS; HEPATIC STEATOSIS; SMALL-INTESTINE; METABOLISM; TRIACYLGLYCEROL; LIPOLYSIS; DROPLETS; CGI-58; COMPARTMENTATION;
D O I
10.1016/j.celrep.2019.07.030
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
As circulating lipid levels are balanced by the rate of lipoprotein release and clearance from the plasma, lipid absorption in the small intestine critically contributes to the maintenance of whole-body lipid homeostasis. Within enterocytes, excessive triglycerides are transiently stored as cytosolic lipid droplets (cLDs), and their mobilization sustains lipid supply during interprandial periods. Using mice lacking adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) exclusively in the intestine (intestine-specific double KO [iDKO]), we show that ATGL/CGI-58 are not involved in providing substrates for chylomicron synthesis. Massive intestinal cLD accumulation in iDKO mice independent of dietary lipids together with inefficient lipid incorporation into cLDs in the early absorption phase demonstrate the existence of a secretion/re-uptake cycle, corroborating the availability of two diverse cLD pools. This study identified ATGL/CGI-58 as critical players in the catabolism of basolaterally (blood) derived lipids and highlights the necessity to modify the current model of intestinal lipid metabolism.
引用
收藏
页码:1923 / +
页数:16
相关论文
共 51 条
[1]   ROLE OF THE GUT IN LIPID HOMEOSTASIS [J].
Abumrad, Nada A. ;
Davidson, Nicholas O. .
PHYSIOLOGICAL REVIEWS, 2012, 92 (03) :1061-1085
[2]   Characteristics and functions of lipid droplets and associated proteins in enterocytes [J].
Beilstein, Frauke ;
Carriere, Veronique ;
Leturque, Armelle ;
Demignot, Sylvie .
EXPERIMENTAL CELL RESEARCH, 2016, 340 (02) :172-179
[3]   CGI-58 knockdown in mice causes hepatic steatosis but prevents diet-induced obesity and glucose intolerance [J].
Brown, J. Mark ;
Betters, Jenna L. ;
Lord, Caleb ;
Ma, Yinyan ;
Han, Xianlin ;
Yang, Kui ;
Alger, Heather M. ;
Melchior, John ;
Sawyer, Janet ;
Shah, Ramesh ;
Wilson, Martha D. ;
Liu, Xiuli ;
Graham, Mark J. ;
Lee, Richard ;
Crooke, Rosanne ;
Shulman, Gerald I. ;
Xue, Bingzhong ;
Shi, Hang ;
Yu, Liqing .
JOURNAL OF LIPID RESEARCH, 2010, 51 (11) :3306-3315
[4]   Increased very low density lipoprotein (VLDL) secretion, hepatic steatosis, and insulin resistance [J].
Choi, Sung Hee ;
Ginsberg, Henry N. .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2011, 22 (09) :353-363
[5]   Triglyceride-rich lipoproteins and cytosolic lipid droplets in enterocytes: Key players in intestinal physiology and metabolic disorders [J].
Demignot, Sylvie ;
Beilstein, Frauke ;
Morel, Etienne .
BIOCHIMIE, 2014, 96 :48-55
[6]   Studies on the Substrate and Stereo/Regioselectivity of Adipose Triglyceride Lipase, Hormone-sensitive Lipase, and Diacylglycerol-O-acyltransferases [J].
Eichmann, Thomas O. ;
Kumari, Manju ;
Haas, Joel T. ;
Farese, Robert V., Jr. ;
Zimmermann, Robert ;
Lass, Achim ;
Zechner, Rudolf .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (49) :41446-41457
[7]  
Encapsula NanoSciences, 2012, SYST ADM CLODR LIP V
[8]   Rapid chylomicron appearance following sequential meals: effects of second meal composition [J].
Evans, K ;
Kuusela, PJ ;
Cruz, ML ;
Wilhelmova, I ;
Fielding, BA ;
Frayn, KN .
BRITISH JOURNAL OF NUTRITION, 1998, 79 (05) :425-429
[9]   Lipid Droplets Finally Get a Little R-E-S-P-E-C-T [J].
Farese, Robert V., Jr. ;
Walther, Tobias C. .
CELL, 2009, 139 (05) :855-860
[10]   Postprandial lipemia: The origin of an early peak studied by specific dietary fatty acid intake during sequential meals [J].
Fielding, BA ;
Callow, J ;
Owen, RM ;
Samra, JS ;
Matthews, DR ;
Frayn, KN .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 1996, 63 (01) :36-41