Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

An Integrated Multi-OMICS Approach Highlights Elevated Non-esterified Fatty Acids Impact BeWo Trophoblast Metabolism and Lipid Processing

Zachary JW Easton
ORCID logo ,
Ousseynou Sarr
,
Lin Zhao
,
Adriana Z Buzatto
ORCID logo ,
Xian Luo
ORCID logo ,
Shuang Zhao
,
Liang Li
ORCID logo ,
Timothy RH Regnault
* ORCID logo
Version 1 : Received: 13 June 2023 / Approved: 14 June 2023 / Online: 14 June 2023 (09:44:17 CEST)

A peer-reviewed article of this Preprint also exists.

Easton, Z.J.W.; Sarr, O.; Zhao, L.; Buzatto, A.Z.; Luo, X.; Zhao, S.; Li, L.; Regnault, T.R.H. An Integrated Multi-OMICS Approach Highlights Elevated Non-Esterified Fatty Acids Impact BeWo Trophoblast Metabolism and Lipid Processing. Metabolites 2023, 13, 883. Easton, Z.J.W.; Sarr, O.; Zhao, L.; Buzatto, A.Z.; Luo, X.; Zhao, S.; Li, L.; Regnault, T.R.H. An Integrated Multi-OMICS Approach Highlights Elevated Non-Esterified Fatty Acids Impact BeWo Trophoblast Metabolism and Lipid Processing. Metabolites 2023, 13, 883.

Abstract

Maternal obesity and gestational diabetes mellitus (GDM) are linked with impaired placental function and early onset of non-communicable cardiometabolic diseases in offspring. Previous studies have highlighted that the dietary non-esterified fatty acids (NEFAs), palmitate (PA) and oleate (OA), key dietary metabolites associated with maternal obesity and GDM, are potential modulators of placental lipid processing. Using the BeWo cell line model, the current study integrated transcriptomic (mRNA microarray), metabolomic, and lipidomic readouts to characterize the underlying impacts of exogenous PA and OA on placental villous trophoblast cell metabolism. Targeted gas chromatography and thin layer chromatography highlighted that saturated and monounsaturated NEFAs differentially impact BeWo cell lipid profiles. Furthermore, cellular lipid profiles differed when exposed to single and multiple NEFA species. Additional multi-omic analyses suggested that PA exposure is associated with enrichment in β-oxidation pathways, while OA exposure is associated with enrichment in anti-inflammatory and antioxidant pathways. Overall, this study further demonstrated that dietary PA and OA are important regulators of placental lipid metabolism. Encouraging appropriate dietary advise and implementing dietary interventions that maintain appropriate placental function by limiting excessive exposure to saturated NEFAs such as PA, will continue to be crucial in the clinical management of at-risk obese and GDM pregnancies.

Keywords

BeWo cells; placental lipid metabolism; fatty acid desaturation; fatty acid elongation; transcriptome; metabolome; lipidome; OMIC integration

Subject

Medicine and Pharmacology, Obstetrics and Gynaecology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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