Biology subjects

Duberg, D.

Publications and source records attributed to Duberg, D..

3 recordsLinked to original sources

bioRxiv2026

Early-life PFAS exposure induces systemic metabolic alterations in plasma and brain in mice

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants associated with adverse health effects, including emerging neurodevelopmental and neurological outcomes. Although PFAS can cross the placental and blood-brain barriers, the metabolic mechanisms underlying their neurotoxicity and potential sex-specific effects remain poorly understood. Here, we investigated the effects of prenatal and early-life exposure to a human-relevant PFAS mixture on plasma and brain metabolism in mice. The mixture contained perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), and perfluorononanoic acid (PFNA) at environmentally relevant, subtoxic concentrations. Mass spectrometry-based metabolomics revealed pronounced, sex-dependent metabolic alterations in both plasma and brain. Female brains exhibited more extensive metabolic changes, particularly in lipid and arachidonic acid metabolism, steroid hormone pathways, and carbohydrate and energy metabolism. In contrast, male brains showed more selective perturbations, predominantly involving amino acid and neuroactive signaling pathways related to neurotransmitter metabolism. These distinct metabolic signatures indicate that early-life PFAS exposure affects brain metabolism through sex-dependent mechanisms. Our findings identify the brain metabolome as a sensitive target of early-life PFAS exposure and emphasize the importance of considering sex as a biological variable when assessing the neurotoxicity of persistent environmental contaminants.

pharmacology and toxicology↗

bioRxiv2025

Metabolic effects and biotransformation of perfluorohexyloctane (F6H8) in human hepatocytes

Perfluorohexyloctane (F6H8) is a semifluorinated alkane recently approved for ophthalmic treatment of dry eye disease. Although considered locally safe for topical use, its structural similarity to persistent per- and polyfluoroalkyl substances (PFAS) raises concerns about systemic accumulation and long-term toxicity. To investigate potential hepatic effects, we examined the metabolic impact of F6H8 exposure in human HepaRG hepatocytes across a broad concentration range representing short- and long-term exposure scenarios. Untargeted metabolic profiling by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-OTOFMS) was performed on intracellular extracts and extracellular media. F6H8 induced pronounced, concentration-dependent metabolic alterations, many of which exhibited non-monotonic responses. Low concentrations primarily affected amino acid, fatty acid, and lipid metabolism, while central carbon metabolism was disrupted only at the highest exposures. Notably, a putative biotransformation product, perfluorohexyloctanoic acid, was detected, suggesting metabolic persistence and conversion to a PFAS-like structure. These findings indicate that F6H8 elicits broad metabolic reprogramming and may not be metabolically inert as previously assumed. Given its clinical use and structural similarity to persistent fluorochemicals, the results highlight the need for comprehensive, long-term safety assessment of F6H8 and related semifluorinated alkanes.

pharmacology and toxicology↗

bioRxiv2019

Prenatal Exposure to Environmental Chemicals Modulates Serum Phospholipids in Newborn Infants, Increasing Later Risk of Type 1 Diabetes

In the last decade, increasing incidence of type 1 diabetes (T1D) stabilized in Finland, a phenomenon that coincides with tighter regulation of perfluoroalkyl substances (PFAS). Here, we quantified PFAS to examine their effects, during pregnancy, on lipid and immune-related markers of T1D risk in children. In a mother-infant cohort (264 dyads), high PFAS exposure during pregnancy associated with decreased cord serum phospholipids and progression to T1D-associated islet autoantibodies in the offspring. This PFAS-lipid association appears exacerbated by increased human leukocyte antigen-conferred risk of T1D in infants. Exposure to a single PFAS compound or a mixture of organic pollutants in non-obese diabetic mice resulted in a lipid profile characterized by a similar decrease in phospholipids, a marked increase of lithocholic acid, and accelerated insulitis. Our findings suggest that PFAS exposure during pregnancy contributes to risk and pathogenesis of T1D in offspring.

molecular biology↗