DEHP and DINP Induce Tissue- and Gender-Specific Disturbances in Fatty Acid and Lipidomic Profiles in Neonatal Mice: A Comparative Study

Abstract

Di-isononyl phthalate (DINP) is considered one of the main industrial alternatives to di­(2-ethylhexyl)­phthalate (DEHP), a well-known chemical with various toxic effects including the disruption with lipid metabolism. However, the potential effects of DINP on lipid metabolism have rarely been investigated in mammals. Our study demonstrated that exposure of neonatal mice to DEHP and DINP at a daily dose of 0.048 or 4.8 mg/kg from postnatal day 0 (PND0) to PND21 caused nonmonotonic as well as tissue- and gender-specific alterations of total fatty acid (FA) compositions in plasma, heart, and adipose tissues. However, the patterns of disruption differed between DEHP- and DINP-treated groups. On the basis of targeted lipidomic analyses, we further identified gender-specific alterations of eight lipid classes in plasma following DEHP or DINP exposure. At the higher dose, DEHP induced decreases in total phosphatidylcholines and phosphatidylinositol (PI) in females and increases in phosphatidylethanolamines (PEs) and triglycerides in males. By contrast, DINP at the higher dose caused alterations of PEs, PIs, phosphatidylserines, and cholesterols exclusively in male mice, but no changes were observed in female pups. Although the most significant dysregulation of lipid metabolism was often observed for the higher dose, the lower one could also disrupt lipid profiles and sometimes its effects may even be more significant than those induced by the higher dose. Our study for the first time identified tissue- and gender-specific disruptions of FA compositions and lipidomic profiles in mice neonatally exposed to DINP. These findings question the suitability of DINP as a safe DEHP substitute and lay a solid foundation for further elucidation of its effects on lipid metabolism and underlying mechanisms.

Lipidomic Changes in Banana (Musa cavendish) during Ripening and Comparison of Extraction by Folch and Bligh–Dyer Methods

“…Mass spectrometer parameters were set as follows: CUR: 25 psi, IonSpray voltage: 5500 V, TEM: 350 °C, GS1:30 psi, GS2:30 psi. The MRM information referred to our previous method with some modifications, and the details are given in Table S2. Lipid annotation was based on our previous and other methods.…”

“…The MRM information referred to our previous method with some modifications, and the details are given in Table S2. Lipid annotation was based on our previous and other methods. Concentrations of each lipid species were calculated by relating the peak areas of each species to the peak area of the corresponding internal standard using Analyst 1.6.3 software (AB Sciex, U.S.A.), and normalized by wet weight.…”

“…Instrumental Analysis. Targeted lipidomics were analyzed on an ExionLC AD ultrahigh performance LC (UHPLC, AB Sciex, Toronto, Canada) coupled to an AB Sciex Q TRAP 5500 mass spectrometer, equipped with a Zorbax Eclipse Plus C18 column (2.1 mm × 50 mm, 1.8 μm particle size, Agilent Technologies, U.S.A.) according to our previous publication 22 with modifications on the LC conditions. Sample injection volume was 5 μL.…”

Metabolomic Characterizations of Fullerene Nanomaterials Potentiate Muscle of Clownfish (Amphiprion Ocellaris)

“…Furthermore, the phosphopantetheinyl portion of CoA is a crucial component of acyl carrier protein, essential for the biosynthesis of fatty acid and lipid metabolism [23]. In our study, some lipids and lipid-like molecules were identified as core elements, these affected lipid metabolism mainly contain the general functions of energy storage, cell membrane composition and signal transmission and molecular recognition processes [24][25][26]. Fullerene nanoparticles stimulated the release of arachidonic acid from clownfish cells and arachidonic acid (AA) from membrane phospholipids via phospholipase A2S, which may be related to the pathophysiological events [27].…”

A Novel Mechanism of Monoethylhexyl Phthalate in Lipid Accumulation via Inhibiting Fatty Acid Beta-Oxidation on Hepatic Cells

“…Previous in vitro and in vivo experiments confirmed that MEHP as an active compound can have impact on lipolysis and glycolysis metabolism, resulting in lipid accumulation. − The possible mechanisms of MEHP-induced lipid metabolism dysregulation may be due to its capability in inhibiting the Janus kinase 2-signal transducer and activator of the transcription protein 5 (JAK2/STAT5) pathway, working as the agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ) and disturbing the mitogen-activated protein kinase (MAPK) pathway . It was well known that the JAK2/STAT5 signaling pathway is involved in lipogenesis, and PPAR-γ participates in regulating the expression of cellular lipids .…”