Maternal obesity alters placental lysophosphatidylcholines, lipid storage, and the expression of genes associated with lipid metabolism

Bidne, Katie L; Rister, Alana L.; McCain, Andrea R.; Hitt, Brianna D.; Dodds, Eric D.; Wood, Jennifer R.

doi:10.1093/biolre/ioaa191

Cited by 10 publications

(5 citation statements)

References 59 publications

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“…In a human study, Yamazaki et al [ 98 ] showed that even placental pathologies due to maternal (gestational hypertension or preeclampsia) or fetal (small for gestational age) diseases may disturb the lipid composition in the terminal and stem villi at delivery. In a mouse study, a US research group [ 99 ] showed that maternal diet and obesity strongly influence the lipid composition of the placenta of mice on gestational day 12.5: there was a 2.5 to 6-fold increase in PC36:1, PC38:3, LPC16:1, LPC18:1, and LPC20:1 in the decidua of the obese group following a Western diet compared to lean mice on a normal diet.…”

Section: Discussionmentioning

confidence: 99%

Lipid Changes in the Peri-Implantation Period with Mass Spectrometry Imaging: A Systematic Review

Gitta

Márk

Szentpéteri

et al. 2023

Life

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Mass spectrometry imaging is a sensitive method for detecting molecules in tissues in their native form. Lipids mainly act as energy stores and membrane constituents, but they also play a role in lipid signaling. Previous studies have suggested an important role of lipids in implantation; therefore, our aim was to investigate the lipid changes during this period based on the available literature. The systematic literature search was performed on Ovid MEDLINE, Cochrane Library, Embase, and LILACS. We included studies about lipid changes in the early embryonal stage of healthy mammalian development published as mass spectrometry imaging. The search retrieved 917 articles without duplicates, and five articles were included in the narrative synthesis of the results. Two articles found a different spatial distribution of lipids in the early bovine embryo and receptive uterus. Three articles investigated lipids in mice in the peri-implantation period and found a different spatial distribution of several glycerophospholipids in both embryonic and maternal tissues. Although only five studies from three different research groups were included in this systematic review, it is clear that the spatial distribution of lipids is diverse in different tissues and their distribution varies from day to day. This may be a key factor in successful implantation, but further studies are needed to elucidate the exact mechanism.

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Section: Discussionmentioning

confidence: 99%

Lipid Changes in the Peri-Implantation Period with Mass Spectrometry Imaging: A Systematic Review

Gitta

Márk

Szentpéteri

et al. 2023

Life

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“…Several reports have suggested that maternal obesity alters the placental architecture and negatively impacts fetal growth and development [7][8][9][10]. Placental lipid accumulation is also dramatically increased in obese mothers as compared to lean mothers [11]. A recent study obtained obese placenta from the first trimester of pregnancy and showed increased lipid accumulation and altered expression of major lipid metabolic genes in the placenta [9].…”

Section: Introductionmentioning

confidence: 99%

Palmitate induces integrated stress response and lipoapoptosis in trophoblasts

Sahoo,

Krishnamoorthy,

Wood

et al. 2024

Cell Death Dis

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Maternal obesity increases the risk of childhood obesity and programs the offspring to develop metabolic syndrome later in their life. Palmitate is the predominant saturated free fatty acid (FFA) that is transported across the placenta to the fetus. We have recently shown that saturated FFA in the maternal circulation as a result of increased adipose tissue lipolysis in third trimester of pregnancy induces trophoblast lipoapoptosis. Here, we hypothesized that palmitate induces integrated stress response by activating mitogen-activated protein kinases (MAPKs), endoplasmic reticulum (ER) stress and granular stress and lipoapoptosis in trophoblasts. Choriocarcinoma-derived third-trimester placental trophoblast-like cells (JEG-3 and JAR) referred as trophoblasts were exposed to various concentrations of palmitate (PA). Apoptosis was assessed by nuclear morphological changes and caspase 3/7 activity. Immunoblot and immunofluorescence analysis was performed to measure the activation of MAPKs, ER stress and granular stress response pathways. Trophoblasts exposed to pathophysiological concentrations of PA showed a concentration-dependent increase in trophoblast lipoapoptosis. PA induces a caspase-dependent trophoblast lipoapoptosis. Further, PA induces MAPK activation (JNK and ERK) via phosphorylation, and activation of ER stress as evidenced by an increased phosphorylation eIF2α & IRE1α. PA also induces the activation of stress granules formation. Two pro-apoptotic transcriptional mediators of PA-induced trophoblast lipoapoptosis, CHOP and FoxO3 have increased nuclear translocation. Mechanistically, PA-induced JNK is critical for trophoblast lipoapoptosis. However, PA-induced activation of ERK and stress granule formation were shown to be cell survival signals to combat subcellular stress due to PA exposure. In conclusion, PA induces the activation of integrated stress responses, among which small molecule inhibition of JNK demonstrated that activation of JNK is critical for PA-induced trophoblast lipoapoptosis and small molecule activation of stress granule formation significantly prevents PA-induced trophoblast lipoapoptosis.

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“…These omic-based readouts have demonstrated the presence of altered neutral and polar lipid profiles (highlighted by changes in underlying fatty acid (FA) composition) in the placentae from obese and GDM pregnancies [ 38 , 39 , 40 , 41 , 42 ]. In addition, pre-clinical mouse models of diet-induced maternal pre-gestational obesity have also described metabolomic and transcriptomic markers associated with altered placental lipid composition and metabolism [ 43 , 44 ]. Overall, the current literature has highlighted that abnormal lipid processing occurs in the obese and diabetic placenta.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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 advice and implementing dietary interventions to maintain appropriate placental function by limiting excessive exposure to saturated NEFAs remain crucial in managing at-risk obese and GDM pregnancies.

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Maternal obesity alters placental lysophosphatidylcholines, lipid storage, and the expression of genes associated with lipid metabolism

Cited by 10 publications

References 59 publications

Lipid Changes in the Peri-Implantation Period with Mass Spectrometry Imaging: A Systematic Review

Lipid Changes in the Peri-Implantation Period with Mass Spectrometry Imaging: A Systematic Review

Palmitate induces integrated stress response and lipoapoptosis in trophoblasts

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

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