دورية أكاديمية
أعرض في EDS

Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen.

التفاصيل البيبلوغرافية
العنوان: Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen.
المؤلفون: Yang Y; Department of Medicine and.; Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, California, USA., Beigneux AP; Department of Medicine and., Song W; Department of Medicine and., Nguyen LP; Department of Medicine and., Jung H; Department of Medicine and., Tu Y; Department of Medicine and., Weston TA; Department of Medicine and., Tran CM; Department of Medicine and., Xie K; Department of Medicine and., Yu RG; Department of Medicine and., Tran AP; Department of Medicine and., Miyashita K; Department of Clinical Laboratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan., Nakajima K; Department of Clinical Laboratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan., Murakami M; Department of Clinical Laboratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan., Chen YQ; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA., Zhen EY; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA., Kim JR; Department of Medicine and., Kim PH; Department of Medicine and., Birrane G; Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA., Tontonoz P; Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, California, USA., Ploug M; Finsen Laboratory, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark., Konrad RJ; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA., Fong LG; Department of Medicine and., Young SG; Department of Medicine and.; Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
المصدر: The Journal of clinical investigation [J Clin Invest] 2023 Dec 01; Vol. 133 (23). Date of Electronic Publication: 2023 Dec 01.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
مواضيع طبية MeSH: Hypertriglyceridemia*/genetics , Hypertriglyceridemia*/metabolism , Receptors, Lipoprotein*/genetics , Receptors, Lipoprotein*/metabolism , Apolipoprotein A-V*/genetics, Animals ; Mice ; Capillaries/metabolism ; Lipoprotein Lipase/genetics ; Lipoprotein Lipase/metabolism ; Triglycerides/blood
مستخلص: Why apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia has remained unclear, but we have suspected that the underlying cause is reduced amounts of lipoprotein lipase (LPL) in capillaries. By routine immunohistochemistry, we observed reduced LPL staining of heart and brown adipose tissue (BAT) capillaries in Apoa5-/- mice. Also, after an intravenous injection of LPL-, CD31-, and GPIHBP1-specific mAbs, the binding of LPL Abs to heart and BAT capillaries (relative to CD31 or GPIHBP1 Abs) was reduced in Apoa5-/- mice. LPL levels in the postheparin plasma were also lower in Apoa5-/- mice. We suspected that a recent biochemical observation - that APOA5 binds to the ANGPTL3/8 complex and suppresses its capacity to inhibit LPL catalytic activity - could be related to the low intracapillary LPL levels in Apoa5-/- mice. We showed that an ANGPTL3/8-specific mAb (IBA490) and APOA5 normalized plasma triglyceride (TG) levels and intracapillary LPL levels in Apoa5-/- mice. We also showed that ANGPTL3/8 detached LPL from heparan sulfate proteoglycans and GPIHBP1 on the surface of cells and that the LPL detachment was blocked by IBA490 and APOA5. Our studies explain the hypertriglyceridemia in Apoa5-/- mice and further illuminate the molecular mechanisms that regulate plasma TG metabolism.
References: JCI Insight. 2017 Oct 19;2(20):. (PMID: 29046479)
J Biol Chem. 2004 Jul 2;279(27):27941-7. (PMID: 15090553)
J Biol Chem. 1995 Oct 13;270(41):24525-31. (PMID: 7592670)
J Lipid Res. 2005 Sep;46(9):2015-22. (PMID: 15961791)
J Biol Chem. 2011 Jun 3;286(22):19735-43. (PMID: 21478160)
J Clin Invest. 2005 Oct;115(10):2862-9. (PMID: 16200213)
J Lipid Res. 2020 Sep;61(9):1253. (PMID: 32327484)
J Clin Invest. 1995 Dec;96(6):2555-68. (PMID: 8675619)
J Lipid Res. 2022 May;63(5):100198. (PMID: 35307397)
J Biol Chem. 2008 Dec 12;283(50):34511-8. (PMID: 18845532)
J Lipid Res. 2008 Mar;49(3):572-80. (PMID: 18056685)
J Lipid Res. 2017 Jun;58(6):1166-1173. (PMID: 28413163)
Atherosclerosis. 2014 Mar;233(1):97-103. (PMID: 24529129)
Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16109-14. (PMID: 24043787)
J Lipid Res. 2021;62:100149. (PMID: 34780727)
J Biol Chem. 2009 Oct 30;284(44):30240-7. (PMID: 19726683)
Sci Rep. 2017 Dec 20;7(1):17921. (PMID: 29263402)
Proc Natl Acad Sci U S A. 2023 Feb 14;120(7):e2214081120. (PMID: 36763533)
Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1723-1732. (PMID: 30559189)
Arterioscler Thromb Vasc Biol. 2019 Mar;39(3):373-386. (PMID: 30700132)
Science. 2001 Oct 5;294(5540):169-73. (PMID: 11588264)
Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2573-9. (PMID: 16166565)
J Biol Chem. 2005 Jun 3;280(22):21553-60. (PMID: 15774484)
J Lipid Res. 2008 Aug;49(8):1846-54. (PMID: 18441017)
J Lipid Res. 2020 Aug;61(8):1203-1220. (PMID: 32487544)
Biochem Biophys Res Commun. 2004 Jun 25;319(2):397-404. (PMID: 15178420)
Comp Biochem Physiol B Biochem Mol Biol. 1998 Oct;121(2):201-12. (PMID: 9972295)
Proc Natl Acad Sci U S A. 2021 Mar 23;118(12):. (PMID: 33723082)
Mol Metab. 2017 Oct;6(10):1137-1149. (PMID: 29031715)
J Lipid Res. 2021;62:100068. (PMID: 33762177)
Cell Metab. 2007 Apr;5(4):279-91. (PMID: 17403372)
Elife. 2016 Jan 03;5:e12095. (PMID: 26725083)
Nature. 2015 Feb 5;518(7537):102-6. (PMID: 25487149)
Diabetes Metab J. 2020 Apr;44(2):213-221. (PMID: 32347023)
J Lipid Res. 2020 Oct;61(10):1347-1359. (PMID: 32690595)
J Biol Chem. 2005 Jul 8;280(27):25383-7. (PMID: 15878877)
J Intern Med. 2008 Apr;263(4):450-8. (PMID: 18324930)
Clin Chem. 2005 Feb;51(2):351-9. (PMID: 15528295)
Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):11630-5. (PMID: 26305978)
Clin Genet. 2004 Feb;65(2):126-30. (PMID: 14984471)
Front Cell Dev Biol. 2021 Jul 15;9:702508. (PMID: 34336854)
Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):411-7. (PMID: 15591215)
Cell Metab. 2010 Jul 7;12(1):42-52. (PMID: 20620994)
J Biol Chem. 2015 May 8;290(19):11865-77. (PMID: 25809481)
Methods. 2001 Dec;25(4):402-8. (PMID: 11846609)
Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):455-62. (PMID: 18258818)
Proc Natl Acad Sci U S A. 2020 Feb 25;117(8):4337-4346. (PMID: 32034094)
Chem Phys Lipids. 2006 Sep;143(1-2):22-8. (PMID: 16806135)
J Lipid Res. 2007 Dec;48(12):2788-91. (PMID: 17872590)
JCI Insight. 2020 Sep 3;5(17):. (PMID: 32730227)
Proc Natl Acad Sci U S A. 2023 Feb 21;120(8):e2219833120. (PMID: 36787365)
Am J Pathol. 1992 Oct;141(4):843-54. (PMID: 1415479)
Circulation. 1998 Nov 10;98(19):2088-93. (PMID: 9808609)
Elife. 2016 Dec 08;5:. (PMID: 27929370)
J Biol Chem. 2001 Nov 30;276(48):44512-20. (PMID: 11577099)
J Lipid Res. 2017 Jul;58(7):1453-1461. (PMID: 28476858)
J Clin Invest. 2022 Mar 1;132(5):. (PMID: 35229724)
Cell Metab. 2014 May 6;19(5):849-60. (PMID: 24726386)
Metabolism. 1988 Jun;37(6):597-601. (PMID: 3374326)
معلومات مُعتمدة: R01 HL087228 United States HL NHLBI NIH HHS; R01 HL171737 United States HL NHLBI NIH HHS; P01 HL146358 United States HL NHLBI NIH HHS; P01 HL090553 United States HL NHLBI NIH HHS; R35 HL139725 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: Endothelial cells; Lipoproteins; Metabolism; Mouse models; Vascular Biology
المشرفين على المادة: EC 3.1.1.34 (Lipoprotein Lipase)
0 (Receptors, Lipoprotein)
0 (Triglycerides)
0 (Apoa5 protein, mouse)
0 (Apolipoprotein A-V)
تواريخ الأحداث: Date Created: 20231012 Date Completed: 20240131 Latest Revision: 20240710
رمز التحديث: 20240710
مُعرف محوري في PubMed: PMC10688983
DOI: 10.1172/JCI172600
PMID: 37824203
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI172600