Lysophosphatidylethanolamine Affects Lipid Accumulation and Metabolism in a Human Liver-Derived Cell Line

Yamamoto, Yusuke; Sakurai, ﻿Toshihiro; Chen, Zhen; Inoue, Nao; Chiba, Hitoshi; Hui, Shu‐Ping

doi:10.3390/nu14030579

Cited by 47 publications

(24 citation statements)

References 47 publications

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“…A recent study reported that LPE supplementation induces enhanced cellular lipid droplet formation and increased lipid profiles, including TG-, CE-, PE-, LPE-, and PC-containing linoleic acyl triacylglycerol in human liver-derived cell line C3A. 46 The increased LPC and LPE contents observed in the present study could be potentially attributable to increased biosynthesis or increased PLA2 activity, which needs further studies.…”

Section: Discussionmentioning

confidence: 55%

Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate (EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D Hepatospheroid Cell Culture

Negi

Gadara

Kohoutek

et al. 2023

Environ. Sci. Technol.

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The present study aims to evaluate the effects of repeated exposure to 2-ethylhexyldiphenyl phosphate (EHDPP) on human liver cells. In vitro three-dimensional (3D) hepatospheroid cell culture was utilized to explore the potential mechanisms of EHDPP-mediated metabolic disruption through morphological, transcriptional, and biochemical assays. Lipidomics analysis was performed on the individual hepatospheroids to investigate the effects on intracellular lipid profiles, followed by hepatospheroid morphology, growth, functional parameters, and cytotoxicity evaluation. The possible mechanisms were delineated using the gene-level analysis by assessing the expression of key genes encoding for hepatic lipid metabolism. We revealed that exposure to EHDPP at 1 and 10 μM for 7 days alters the lipid profile of human 3D hepatospheroids. Dysregulation in several lipid classes, including sterol lipids (cholesterol esters), sphingolipids (dihydroceramide, hexosylceramide, ceramide, sphingomyelin), glycerolipids (triglycerides), glycerophospholipids, and fatty acyls, was noted along with alteration in genes including ACAT1, ACAT2, CYP27A1, ABCA1, GPAT2, PNPLA2, PGC1α, and Nrf2. Our study brings a novel insight into the metabolic disrupting effects of EHDPP and demonstrates the utility of hepatospheroids as an in vitro cell culture model complemented with omics technology (e.g., lipidomics) for mechanistic toxicity studies.

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Section: Discussionmentioning

confidence: 55%

Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate (EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D Hepatospheroid Cell Culture

Negi

Gadara

Kohoutek

et al. 2023

Environ. Sci. Technol.

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“…As a family, lysophospholipids play a role as precursors for membrane biosynthesis and as signaling molecules, promoting plaque formation, which leads to atherosclerosis [ 89 , 90 , 91 , 92 , 93 ]. LysoPE (18:2) in particular, has been shown to induce lipid droplet formation and accumulation (within hepatocytes) and is reported in cases of non-ST-elevation myocardial infarction (NSTEMI) [ 94 , 95 ]. Thus, the suppression of this metabolite by probiotic supplementation may result in a reduction of the precursors to cardiovascular disease.…”

Section: Resultsmentioning

confidence: 99%

“…Finally, through an in-depth analysis of the basal, higher-fat, and higher-fat+probiotic cohorts, we discovered that with probiotic supplementation, some potentially aberrant metabolites identified in the higher-fat cohort tissues (notably, S-adenosylhomocysteine and glutathione in the brain cortex, indoxyl sulfate in the kidney, and LysoPE (18:2) in the heart) revert to levels associated with those found in pigs fed a healthy, nutritionally balanced diet. While it remains unknown as to why these higher-fat altered metabolites are particularly sensitive to probiotic supplementation, we can speculate that their reversion to a healthy-associated metabotype may promote healthy neurocognitive function, clear toxic by-products of protein putrefaction, and reduce hallmarks of atherosclerosis [ 28 , 29 , 30 , 31 , 36 , 37 , 52 , 53 , 90 , 91 , 92 , 93 , 94 , 95 , 96 ]. Coupled together, the reversion of the intracellular concentration of these metabolites to a level akin to a healthy diet depicts the beneficial nature of probiotic supplementation and may show its usefulness as a prophylactic approach to address obesity and metabolic syndrome.…”

Section: Discussionmentioning

confidence: 99%

LC-QToF-Based Metabolomics Identifies Aberrant Tissue Metabolites Associated with a Higher-Fat Diet and Their ‘Reversion to Healthy’ with Dietary Probiotic Supplementation

et al. 2023

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Over 33% of Americans are labeled as obese, leading the World Health Organization to designate obesity as a major public health problem. One consequence of obesity is the development of metabolic syndrome, a condition which has been correlated to an increased risk for developing cardiovascular disease and Type 2 diabetes. Prolonged ingestion of a higher-fat diet, one cause of obesity, results in alterations to the gut microbiome. These alterations are implicated to have a profound role in the evolution and progression of obesity-linked diseases. Probiotics are associated with positive health effects such as limiting pathogen colonization, aiding in digestion, and vitamin synthesis. Using Ossabaw pigs as a model for obesity, and in conjunction with our previous research, we performed an in-depth, nontargeted, metabolomic analysis on select organs to elucidate the effects of dietary supplementation with the probiotic Lacticaseibacillus paracasei. We focused our analysis on the effects of probiotic supplementation on a higher-fat (obesogenic) diet and a nutritionally balanced diet. Notably, our findings reveal that the brain cortex is highly sensitive to dietary influencers, and with probiotic supplementation, several aberrant metabolites associated with a higher-fat diet revert to healthy levels, thus demonstrating the potential for a probiotic intervention for obesity-linked disease.

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“…In vitro, LPC 16:0 and LPC 18:0 promote lipid accumulation and apoptosis [ 62 , 63 ]. LPE 18:2 activates G-protein-coupled receptor signaling and increases lipid accumulation [ 65 , 66 ], while serum LPE 16:0 associates with diabetes mellitus [ 67 ]. LPG is the agonist of G-protein-coupled receptor 55 and induces inflammation in macrophages [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Adipokine chemerin overexpression in trophoblasts leads to dyslipidemia in pregnant mice: implications for preeclampsia

et al. 2023

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Background The adipokine chemerin regulates adipogenesis and the metabolic function of both adipocytes and liver. Chemerin is elevated in preeclamptic women, and overexpression of chemerin in placental trophoblasts induces preeclampsia-like symptoms in mice. Preeclampsia is known to be accompanied by dyslipidemia, albeit via unknown mechanisms. Here, we hypothesized that chemerin might be a contributor to dyslipidemia. Methods Serum lipid fractions as well as lipid-related genes and proteins were determined in pregnant mice with chemerin overexpression in placental trophoblasts and chemerin-overexpressing human trophoblasts. In addition, a phospholipidomics analysis was performed in chemerin-overexpressing trophoblasts. Results Overexpression of chemerin in trophoblasts increased the circulating and placental levels of cholesterol rather than triglycerides. It also increased the serum levels of lysophosphatidic acid, high-density lipoprotein cholesterol (HDL-C), and and low-density lipoprotein cholesterol (LDL-C), and induced placental lipid accumulation. Mechanistically, chemerin upregulated the levels of peroxisome proliferator-activated receptor g, fatty acid-binding protein 4, adiponectin, sterol regulatory element-binding protein 1 and 2, and the ratio of phosphorylated extracellular signal-regulated protein kinase (ERK)1/2 / total ERK1/2 in the placenta of mice and human trophoblasts. Furthermore, chemerin overexpression in human trophoblasts increased the production of lysophospholipids and phospholipids, particularly lysophosphatidylethanolamine. Conclusions Overexpression of placental chemerin production disrupts trophoblast lipid metabolism, thereby potentially contributing to dyslipidemia in preeclampsia.

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Lysophosphatidylethanolamine Affects Lipid Accumulation and Metabolism in a Human Liver-Derived Cell Line

Cited by 47 publications

References 47 publications

Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate (EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D Hepatospheroid Cell Culture

Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate (EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D Hepatospheroid Cell Culture

LC-QToF-Based Metabolomics Identifies Aberrant Tissue Metabolites Associated with a Higher-Fat Diet and Their ‘Reversion to Healthy’ with Dietary Probiotic Supplementation

Adipokine chemerin overexpression in trophoblasts leads to dyslipidemia in pregnant mice: implications for preeclampsia

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