Journal article
Obesity Reduces Maternal Blood Triglyceride Concentrations by Reducing Angiopoietin-Like Protein 4 Expression in Mice
Diabetes (New York, N.Y.), Vol.69(6), pp.1100-1109
02/12/2020
DOI: 10.2337/db19-1181
PMCID: PMC7243287
PMID: 32051149
Abstract
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.
Details
- Title: Subtitle
- Obesity Reduces Maternal Blood Triglyceride Concentrations by Reducing Angiopoietin-Like Protein 4 Expression in Mice
- Creators
- Liping Qiao - University of California, San DiegoShwetha K. Shetty - University of IowaKathryn M. Spitler - University of IowaJean-Sebastien Wattez - University of California, San DiegoBrandon S.J. Davies - University of IowaJianhua Shao - University of California, San Diego
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.69(6), pp.1100-1109
- Publisher
- American Diabetes Association
- DOI
- 10.2337/db19-1181
- PMID
- 32051149
- PMCID
- PMC7243287
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Grant note
- 1–16-IBS-272 / ; HL-130146 / ; DK-095132; DK-113007 / ;
- Language
- English
- Date published
- 02/12/2020
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Health and Human Physiology
- Record Identifier
- 9984288725302771
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