title: Lipidomic and spatio-temporal imaging of fat by mass spectrometry in mice duodenum during lipid digestion.
abstract: Intestinal absorption of dietary fat is a complex process mediated by enterocytes leading to lipid assembly and secretion of circulating lipoproteins as chylomicrons, vLDL and intestinal HDL (iHDL). Understanding lipid digestion is of importance knowing the correlation between excessive fat absorption and atherosclerosis. By using time-of-flight secondary ion mass spectrometry (TOF-SIMS), we illustrated a spatio-temporal localization of fat in mice duodenum, at different times of digestion after a lipid gavage, for the first time. Fatty acids progressively increased in enterocytes as well as taurocholic acid, secreted by bile and engaged in the entero-hepatic re-absorption cycle. Cytosolic lipid droplets (CLD) from enterocytes were originally purified separating chylomicron-like, intermediate droplets and smaller HDL-like. A lipidomic quantification revealed their contents in triglycerides, free and esterified cholesterol, phosphatidylcholine, sphingomyelin and ceramides but also in free fatty acids, mono- and di-acylglycerols. An acyl-transferase activity was identified and the enzyme monoacylglycerol acyl transferase 2 (MGAT2) was immunodetected in all CLD. The largest droplets was also shown to contain the microsomal triglyceride transfer protein (MTTP), the acyl-coenzyme A-cholesterol acyltransferases (ACAT) 1 and 2, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). This highlights the fact that during the digestion of fats, enterocyte CLD contain some enzymes involved in the different stages of the metabolism of diet fatty acids and cholesterol, in anticipation of the crucial work of endoplasmic reticulum in the process. The data further underlines the dual role of chylomicrons and iHDL in fat digestion which should help to efficiently complement lipid-lowering therapy.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique (CNRS), Gif-sur-Yvette, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Seyer
authors.forename: Michela
authors.initials: M
authors.lastname: Cantiello
authors.forename: Justine
authors.initials: J
authors.lastname: Bertrand-Michel
authors.forename: Véronique
authors.initials: V
authors.lastname: Roques
authors.forename: Michel
authors.initials: M
authors.lastname: Nauze
authors.forename: Valérie
authors.initials: V
authors.lastname: Bézirard
authors.forename: Xavier
authors.initials: X
authors.lastname: Collet
authors.forename: David
authors.initials: D
authors.lastname: Touboul
authors.forename: Alain
authors.initials: A
authors.lastname: Brunelle
authors.forename: Christine
authors.initials: C
authors.lastname: Coméra
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D004386:Duodenum / Q000166:cytology / Q000378:metabolism*; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression; D007408:Intestinal Absorption; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D000097587:Sterol O-Acyltransferase 2; D000217:Acyltransferases
chemical_list: D000101:Acetyl-CoA C-Acetyltransferase; D002352:Carrier Proteins; D002784:Cholesterol; D002914:Chylomicrons; D004041:Dietary Fats; D005227:Fatty Acids; D008049:Lipase; D008075:Lipoproteins, HDL; D017351:N-Acetylglucosaminyltransferases; D002787:Sterol Esterase; D002785:Sterol O-Acyltransferase; D013656:Taurocholic Acid; D014280:Triglycerides; D000097587:Sterol O-Acyltransferase 2; C106092:microsomal triglyceride transfer protein; C506641:Acat1 protein, mouse; C063313:alpha-1,6-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
references.citation: J Lipid Res. 2008 Feb;49(2):438-54
references.pmid: 18025000
references.citation: Am J Physiol Endocrinol Metab. 2009 Jun;296(6):E1183-94
references.pmid: 19158321
references.citation: J Biol Chem. 2006 Mar 17;281(11):7214-9
references.pmid: 16421100
references.citation: J Clin Invest. 1972 Oct;51(10):2686-92
references.pmid: 4341437
references.citation: J Clin Invest. 2005 May;115(5):1290-7
references.pmid: 15841205
references.citation: J Lipid Res. 1977 Jul;18(4):496-511
references.pmid: 894141
references.citation: Atherosclerosis. 2010 Jun;210(2):362-5
references.pmid: 20116793
references.citation: Anal Chem. 2009 Apr 15;81(8):2823-31
references.pmid: 19296690
references.citation: J Biol Chem. 2003 Apr 18;278(16):13611-4
references.pmid: 12618427
references.citation: Am J Physiol Gastrointest Liver Physiol. 2011 May;300(5):G803-14
references.pmid: 21350192
references.citation: J Lipid Res. 2010 May;51(5):945-56
references.pmid: 19965594
references.citation: J Biol Chem. 2006 Feb 17;281(7):4075-86
references.pmid: 16354657
references.citation: Metabolism. 2000 Apr;49(4):467-72
references.pmid: 10778870
references.citation: Biochim Biophys Acta. 2009 Dec;1791(12):1173-80
references.pmid: 19698802
references.citation: Can J Biochem Physiol. 1959 Aug;37(8):911-7
references.pmid: 13671378
references.citation: Mol Cell Biochem. 2009 Jun;326(1-2):79-86
references.pmid: 19116776
references.citation: J Biol Chem. 2001 Jul 6;276(27):25324-35
references.pmid: 11333258
references.citation: Gut. 2010 Jul;59(7):888-95
references.pmid: 20581237
references.citation: J Lipid Res. 2007 Apr;48(4):837-47
references.pmid: 17210984
references.citation: J Lipid Res. 1964 Apr;5:225-31
references.pmid: 14174009
references.citation: J Lipid Res. 2009 Nov;50(11):2148-56
references.pmid: 19696439
references.citation: Traffic. 2008 Mar;9(3):338-52
references.pmid: 18088320
references.citation: Can J Cardiol. 2011 Mar-Apr;27(2):183-91
references.pmid: 21459267
references.citation: Anal Bioanal Chem. 2010 Jan;396(1):151-62
references.pmid: 19711060
references.citation: J Lipid Res. 2009 Jun;50(6):1080-9
references.pmid: 19218555
references.citation: J Lipid Res. 2012 Jan;53(1):95-104
references.pmid: 22045928
references.citation: J Lipid Res. 2009 Nov;50(11):2235-44
references.pmid: 19454765
references.citation: J Lipid Res. 1998 Aug;39(8):1543-57
references.pmid: 9717714
references.citation: Am J Cardiol. 2000 Nov 1;86(9):943-9
references.pmid: 11053704
references.citation: J Lipid Res. 2005 Jul;46(7):1491-501
references.pmid: 15834127
references.citation: Science. 2004 Feb 20;303(5661):1201-4
references.pmid: 14976318
references.citation: Arterioscler Thromb Vasc Biol. 2009 May;29(5):767-73
references.pmid: 19286631
references.citation: J Biol Chem. 1998 Dec 25;273(52):35132-41
references.pmid: 9857049
references.citation: Biochim Biophys Acta. 2009 Jul;1791(7):679-83
references.pmid: 19272334
references.citation: J Lipid Res. 2007 Aug;48(8):1735-45
references.pmid: 17473178
references.citation: J Lipid Res. 2010 Oct;51(10):3034-45
references.pmid: 20616379
references.citation: Br J Nutr. 2012 May;107(9):1296-304
references.pmid: 21929836
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):243-50
references.pmid: 20206487
references.citation: J Lipid Res. 2007 Sep;48(9):2028-38
references.pmid: 17582142
references.citation: Analyst. 2004 Jun;129(6):483-7
references.pmid: 15152322
references.citation: J Lipid Res. 1995 Nov;36(11):2405-12
references.pmid: 8656078
references.citation: Am J Physiol Gastrointest Liver Physiol. 2008 Apr;294(4):G839-43
references.pmid: 18276831
references.citation: J Biol Chem. 2004 Apr 30;279(18):18878-86
references.pmid: 14966132
references.citation: J Biol Chem. 2008 Oct 31;283(44):29802-11
references.pmid: 18768481
references.citation: Am J Physiol Gastrointest Liver Physiol. 2002 Aug;283(2):G340-6
references.pmid: 12121881
references.citation: Curr Opin Chem Biol. 2011 Oct;15(5):725-32
references.pmid: 21612973
references.citation: Clin Chem. 1993 Jun;39(6):960-4
references.pmid: 8504564
references.citation: J Cell Physiol. 2005 Mar;202(3):767-76
references.pmid: 15389567
references.citation: Biol Cell. 2011 Nov;103(11):499-517
references.pmid: 21787361
references.citation: J Biol Chem. 1994 Apr 15;269(15):11572-7
references.pmid: 8157689
references.citation: J Biol Chem. 2003 Feb 21;278(8):6510-5
references.pmid: 12482847
references.citation: J Biol Chem. 2007 Jul 6;282(27):19493-501
references.pmid: 17507371
references.citation: Eur J Nutr. 2001 Aug;40(4):161-7
references.pmid: 11905957
references.citation: FEBS Lett. 2010 Jun 3;584(11):2168-75
references.pmid: 20347811
references.citation: J Am Soc Mass Spectrom. 2005 Oct;16(10):1608-18
references.pmid: 16112869
references.citation: Biochimie. 2011 Jan;93(1):113-9
references.pmid: 20570708
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Sep;293(3):G519-24
references.pmid: 17495031
references.citation: J Ultrastruct Res. 1981 Jul;76(1):15-26
references.pmid: 7277573
references.citation: Anal Chem. 2004 Mar 15;76(6):1550-9
references.pmid: 15018551
references.citation: J Cell Biol. 1962 Dec 1;15(3):541-62
references.pmid: 19866614
references.citation: J Biol Chem. 2003 May 16;278(20):18532-7
references.pmid: 12621063