Maternal eicosapentaenoic acid feeding promotes placental angiogenesis through a Sirtuin-1 independent inflammatory pathway.

Abstract

Maternal overnutrition or obesity is associated with a wide range of metabolic disorders and may impair placental angiogenesis. Previous studies have shown that n-3 polyunsaturated fatty acids (PUFA) promote fetal growth in both rodents and humans. Whether n-3 PUFA impacts on placental angiogenesis in vivo remains unclear. Sirtuin-1 (SIRT1) is a protein deacetylase that plays an important role in regulating inflammation and endothelial function. Little information is available on a putative role of SIRT1 in placental angiogenesis. The goal of this study was to examine the capability of eicosapentaenoic acid (EPA) to regulate angiogenesis and inflammation in SIRT1-deficient placentas. In the present study, male and female SIRT1+/- mice were mated overnight, then primiparous SIRT1+/- mice were fed a 60% kcal HFD or equienergy EPA diet (4.4% EPA-ethyl ester). We found that the EPA diet significantly improved maternal insulin sensitivity and decreased plasma levels of inflammatory factors IL-6 and TNFα concentration. Moreover, EPA treatment promoted fetus growth and placental angiogenesis, and inhibited the hypoxia inducible factor-1α(HIF1α) pathway. SIRT1 deficiency exhibited an opposite effect, leading to decrease in placental angiogenesis and fetal weight. No significant effect was observed between diet and genotype. Here, we reported for the first time that EPA treatment increased the expression of placental inflammatory genes and promoted translocation of NFκB into the nucleus. On the contrary, SIRT1-deficient placentas showed a decreased inflammation state. Together, these data demonstrate a previously unknown role of EPA to promote placental angiogenesis through a SIRT1 independent inflammatory pathway.

• Authors: Jie Peng, Yuanfei Zhou, Zhang Hong, Yinghui Wu, Anle Cai, Mao Xia, Zhao Deng, Yang Yang, Tongxing Song, Jia Xiong, Hongkui Wei, Jian Peng
• Journal: Biochimica et biophysica acta. Molecular and cell biology of lipids (Biochim Biophys Acta Mol Cell Biol Lipids) Vol. 1864 Issue 2 Pg. 147-157 (02 2019) ISSN: 1879-2618 [Electronic] Netherlands
• PMID: 30445165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• Angiogenesis Inducing Agents
• Fatty Acids, Omega-3
• NF-kappa B
• Tumor Necrosis Factor-alpha
• eicosapentaenoic acid ethyl ester
• Eicosapentaenoic Acid
• Sirt1 protein, mouse
• Sirtuin 1

Topics

• Angiogenesis Inducing Agents (metabolism)
• Animals
• Diet, High-Fat
• Dietary Supplements
• Eicosapentaenoic Acid (analogs & derivatives, metabolism, pharmacology)
• Fatty Acids, Omega-3 (metabolism)
• Female
• Inflammation (metabolism)
• Insulin Resistance
• Male
• Maternal Exposure
• Mice
• Mice, Inbred C57BL
• Mice, Inbred ICR
• NF-kappa B (metabolism)
• Neovascularization, Physiologic (drug effects, physiology)
• Obesity (metabolism)
• Placenta (drug effects)
• Pregnancy
• Sirtuin 1 (metabolism, physiology)
• Tumor Necrosis Factor-alpha (metabolism)