Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice

Abstract

Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) decreased the plasma triglyceride in prepartum mice. To identify the fatty acid (FA) species involved and to understand the underlying mechanisms, pregnant Sv/129 wild-type (mPPARα), peroxisome proliferator-activated receptor α-null (Pparα-null) and humanized PPARα (hPPARα) mice were treated with diets containing 0%, 0.01%, 0.05% or 0.1% DEHP. Dams were dissected on gestational day 18 together with fetuses, and on postnatal day 2 together with newborns. n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs in maternal plasma and in liver of wild-type offspring, and representative enzymes for FA desaturation and elongation in maternal liver, were measured. The plasma levels of linoleic acid, α-linolenic acid, palmitic acid and oleic acid were higher in the pregnant control mPPARa mice than in Ppara-null and hPPARa mice. DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPARα mice. Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype-independent manner, while it was lower in the livers of fetuses than pups. DEHP exposure slightly increased hepatic arachidonic acid, α-linolenic acid, palmitoleic acid and oleic acid in fetuses, but not in pups. However, DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice. Taken together, the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPARα mice than in other genotypes, and DEHP exposure decreased these specific FA concentrations only in mPPARα mice, similarly to triglyceride levels.

Exposure to phthalates is associated with lipid profile in peripubertal Mexican youth

“…Three decades ago, Bell observed that dietary administration of DEHP inhibited cholesterolgenesis and decreased blood lipid levels in multiple animal species (7). More recent rodent models (8, 36) suggest that the hypolipidemic effect of DEHP may arise through its interactions with peroxisome proliferator-activated receptor-α (PPAR-α), a ligand-activated transcription factor that can decrease production of LDL-C and triglycerides, and upregulate HDL-C levels through its roles in lipid oxidation and fatty acid synthesis (37, 38). Likewise, our finding that higher peripubertal MEP was associated with lower total cholesterol and LDL-C could be explained by the fact that MEP is an estrogenic compound that may act as a PPAR-γ agonist (39) to reduce circulating lipid levels by promoting uptake and storage of free fatty acids in adipose tissue (40).…”

Prenatal maternal blood triglyceride and fatty acid levels in relation to exposure to di(2-ethylhexyl)phthalate: a cross-sectional study

“…FA levels in maternal blood were determined duplicately by GC-MS as described in detail in our earlier study [17] after extracting lipids according to the method of Folch et al [22]. Nine FA species targeted for measurement included palmitic and stearic acids of saturated FAs, palmitoleic and oleic acids of monounsaturated FAs, LA and arachidonic acid (AA) of the n-6 family, and ALA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of the n-3 family.…”

“…Moreover, prenatal DEHP exposure was reported to correlate with shorter anogenital distance, reduced penile size and incomplete testicular descent [13,14], more non-optimal reflexes [15] and reduced masculine play behavior [16] in male infants, suggesting that possible sex difference exists in DEHP toxicity. Additionally, our group recently reported that maternal exposure to DEHP decreased plasma levels of triglycerides (TG) [1] and four fatty acid (FA) components [17] in prepartum mice, including palmitic acid, oleic acid, linoleic acid (LA), and a-linolenic acid (ALA), which was suspected to correlate with adverse effects of DEHP. However, no information regarding humans is available.…”

Effects of Di-(2-ethylhexyl) Phthalate on Lipid Metabolism by the JAK/STAT Pathway in Rats

“…Human exposure to DEHP is reported to be mainly through ingestion and dermal contact [3]. In recent years, a number of studies have shown that exposure to DEHP can cause abnormal lipid metabolism in humans, which results in numerous health implications such as heart disease, diabetes, and as the most common disorder, obesity [4,5,6]. …”