Obesity Reduces Maternal Blood Triglyceride Concentrations by Reducing Angiopoietin-Like Protein 4 Expression in Mice.

Tytuł:: Obesity Reduces Maternal Blood Triglyceride Concentrations by Reducing Angiopoietin-Like Protein 4 Expression in Mice.
Autorzy:: Qiao L; Department of Pediatrics, University of California San Diego, La Jolla, CA.
Shetty SK; Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, Obesity Research and Education Initiative, University of Iowa Carver College of Medicine, Iowa City, IA.
Spitler KM; Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, Obesity Research and Education Initiative, University of Iowa Carver College of Medicine, Iowa City, IA.
Wattez JS; Department of Pediatrics, University of California San Diego, La Jolla, CA.
Davies BSJ; Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, Obesity Research and Education Initiative, University of Iowa Carver College of Medicine, Iowa City, IA.
Shao J; Department of Pediatrics, University of California San Diego, La Jolla, CA .
Źródło:: Diabetes [Diabetes] 2020 Jun; Vol. 69 (6), pp. 1100-1109. Date of Electronic Publication: 2020 Feb 12.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: Alexandria, VA : American Diabetes Association
Original Publication: [New York, American Diabetes Association]
MeSH Terms:: Angiopoietin-Like Protein 4/*metabolism
Obesity/*blood
Triglycerides/*blood
Angiopoietin-Like Protein 4/genetics ; Animals ; Diet, Fat-Restricted ; Diet, High-Fat ; Dietary Fats/administration & dosage ; Female ; Gene Expression Regulation/drug effects ; Mice ; Mice, Knockout ; Obesity/metabolism ; Pregnancy ; Triglycerides/metabolism ; Uncoupling Protein 1/genetics ; Uncoupling Protein 1/metabolism
References:: Diabetes. 2008 Jul;57(7):1824-33. (PMID: 18375436)
Obesity (Silver Spring). 2011 Jul;19(7):1476-81. (PMID: 21394096)
Diabetes Care. 2013 Sep;36(9):2706-13. (PMID: 23757425)
Biochem Biophys Res Commun. 2012 Aug 10;424(4):786-92. (PMID: 22809513)
Sci Rep. 2016 Jul 20;6:29971. (PMID: 27436227)
Obstet Gynecol. 2001 May;97(5 Pt 1):776-80. (PMID: 11339933)
Am J Physiol Endocrinol Metab. 2018 Dec 1;315(6):E1224-E1231. (PMID: 30277793)
Mol Cell Biol. 2000 Jul;20(14):5343-9. (PMID: 10866690)
PLoS One. 2016 Aug 25;11(8):e0161206. (PMID: 27560495)
J Biol Chem. 2004 Jan 16;279(3):2038-45. (PMID: 14570927)
Oncogene. 2019 Mar;38(13):2351-2363. (PMID: 30518876)
Am J Physiol. 1994 Jun;266(6 Pt 1):E930-5. (PMID: 8023924)
Diabetes. 2017 May;66(5):1126-1135. (PMID: 28073830)
PLoS One. 2012;7(3):e33370. (PMID: 22442686)
PLoS One. 2015 Mar 04;10(3):e0118586. (PMID: 25738800)
J Clin Invest. 2009 Jan;119(1):70-9. (PMID: 19075393)
J Biol Chem. 2000 Sep 15;275(37):28488-93. (PMID: 10862772)
Obesity (Silver Spring). 2014 Mar;22(3):932-8. (PMID: 23853155)
Diabetes. 2015 Sep;64(9):3111-20. (PMID: 25948680)
Biochim Biophys Acta. 2014 Jul;1841(7):919-33. (PMID: 24721265)
Am J Physiol Endocrinol Metab. 2012 Aug 1;303(3):E334-51. (PMID: 22569073)
Biochim Biophys Acta. 1970 Sep 8;210(3):473-82. (PMID: 5528598)
Sci Rep. 2018 Aug 20;8(1):12428. (PMID: 30127377)
Obesity (Silver Spring). 2018 Aug;26(8):1347-1356. (PMID: 29931812)
J Biol Chem. 2002 Sep 13;277(37):33742-8. (PMID: 12097324)
Cell. 2013 May 9;153(4):747-58. (PMID: 23623304)
Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):E1043-52. (PMID: 24591600)
PLoS One. 2015 Sep 01;10(9):e0136701. (PMID: 26325425)
FASEB J. 2013 Oct;27(10):3928-37. (PMID: 23825226)
Diabetes Care. 2011 Oct;34(10):2198-204. (PMID: 21775754)
Int J Obes (Lond). 2015 Apr;39(4):642-9. (PMID: 25777180)
Diabetologia. 2015 Mar;58(3):615-24. (PMID: 25608625)
Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19751-6. (PMID: 23150577)
J Biol Chem. 2009 May 8;284(19):13213-22. (PMID: 19270337)
Nat Med. 2011 Feb;17(2):200-5. (PMID: 21258337)
Placenta. 2013 Nov;34(11):1087-90. (PMID: 24090886)
Diabetes Care. 2008 Sep;31(9):1858-63. (PMID: 18606978)
Endocrinology. 2005 Nov;146(11):4943-50. (PMID: 16081640)
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17450-5. (PMID: 17088546)
J Lipid Res. 1996 Feb;37(2):299-308. (PMID: 9026528)
J Endocrinol. 2007 Aug;194(2):305-12. (PMID: 17641280)
Mol Metab. 2017 Jun 19;6(8):809-818. (PMID: 28752045)
Nat Genet. 2002 Feb;30(2):151-7. (PMID: 11788823)
J Clin Endocrinol Metab. 2013 Feb;98(2):643-52. (PMID: 23337718)
Int J Obes (Lond). 2017 Feb;41(2):317-323. (PMID: 27780978)
J Lipid Res. 2005 Jul;46(7):1484-90. (PMID: 15863837)
Am J Physiol Lung Cell Mol Physiol. 2015 Aug 15;309(4):L360-8. (PMID: 26092997)
Psychoneuroendocrinology. 2015 Oct;60:138-50. (PMID: 26143538)
Clin Epigenetics. 2016 Feb 27;8:22. (PMID: 26925174)
J Lipid Res. 2007 Feb;48(2):278-87. (PMID: 17114807)
BJOG. 2016 Mar;123(4):570-8. (PMID: 25639335)
Grant Information:: R01 DK095132 United States DK NIDDK NIH HHS; R01 DK113007 United States DK NIDDK NIH HHS; R01 HL130146 United States HL NHLBI NIH HHS
Substance Nomenclature:: 0 (Angiopoietin-Like Protein 4)
0 (Angptl4 protein, mouse)
0 (Dietary Fats)
0 (Triglycerides)
0 (Ucp1 protein, mouse)
0 (Uncoupling Protein 1)
Entry Date(s):: Date Created: 20200214 Date Completed: 20201022 Latest Revision: 20211204
Update Code:: 20240105
PubMed Central ID:: PMC7243287
DOI:: 10.2337/db19-1181
PMID:: 32051149
: Czasopismo naukowe

To ensure fetal lipid supply, maternal blood triglyceride (TG) concentrations are robustly elevated during pregnancy. Interestingly, a lower increase in maternal blood TG concentrations has been observed in some obese mothers. We have shown that high-fat (HF) feeding during pregnancy significantly reduces maternal blood TG levels. Therefore, we performed this study to investigate if and how obesity alters maternal blood TG levels. Maternal obesity was established by prepregnant HF (ppHF) feeding, which avoided the dietary effect during pregnancy. We found not only that maternal blood TG concentrations in ppHF dams were remarkably lower than in control dams but also that the TG peak occurred earlier during gestation. Hepatic TG production and intestinal TG absorption were unchanged in ppHF dams, but systemic lipoprotein lipase (LPL) activity was increased, suggesting that increased blood TG clearance contributes to the decreased blood TG concentrations in ppHF dams. Although significantly higher levels of UCP1 protein were observed in interscapular brown adipose tissue (iBAT) of ppHF dams, Ucp1 gene deletion did not restore blood TG concentrations in ppHF dams. Expression of the angiopoietin-like protein 4 (ANGPTL4), a potent endogenous LPL inhibitor, was significantly increased during pregnancy. However, the pregnancy-induced elevation of blood TG was almost abolished in Angptl4 -/- dams. Compared with control dams, Angptl4 mRNA levels were significantly lower in iBAT, gonadal white adipose tissue, and livers of ppHF dams. Importantly, ectopic overexpression of ANGPTL4 restored maternal blood TG concentrations in ppHF dams. Together, these results indicate that ANGPTL4 plays a vital role in increasing maternal blood TG concentrations during pregnancy. Obesity impairs the rise of maternal blood TG concentrations by reducing ANGPTL4 expression in mice.
(© 2020 by the American Diabetes Association.)

Comment in: Diabetes. 2020 Jun;69(6):1087-1089. (PMID: 32434834)

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