Lipidomic Analyses Reveal Modulation of Lipid Metabolism by the PFAS Perfluoroundecanoic Acid (PFUnDA) in Non-Obese Diabetic MiceShow others and affiliations
2021 (English)In: Frontiers in Genetics, E-ISSN 1664-8021, Vol. 12, article id 721507
Article in journal (Refereed) Published
Abstract [en]
Exposure to Per- and polyfluoroalkyl substances (PFAS) has been linked to multiple undesirable health outcomes across a full lifespan, both in animal models as well as in human epidemiological studies. Immunosuppressive effects of PFAS have been reported, including increased risk of infections and suppressed vaccination responses in early childhood, as well as association with immunotoxicity and diabetes. On a mechanistic level, PFAS exposure has been linked with metabolic disturbances, particularly in lipid metabolism, but the underlying mechanisms are poorly characterized. Herein we explore lipidomic signatures of prenatal and early-life exposure to perfluoroundecanoic acid (PFUnDA) in non-obese diabetic (NOD) mice; an experimental model of autoimmune diabetes. Female NOD mice were exposed to four levels of PFUnDA in drinking water at mating, during gestation and lactation, and during the first weeks of life of female offspring. At offspring age of 11-12 weeks, insulitis and immunological endpoints were assessed, and serum samples were collected for comprehensive lipidomic analyses. We investigated the associations between exposure, lipidomic profile, insulitis grade, number of macrophages and apoptotic, active-caspase-3-positive cells in pancreatic islets. Dose-dependent changes in lipidomic profiles in mice exposed to PFUnDA were observed, with most profound changes seen at the highest exposure levels. Overall, PFUnDA exposure caused downregulation of phospholipids and triacylglycerols containing polyunsaturated fatty acids. Our results show that PFUnDA exposure in NOD mice alters lipid metabolism and is associated with pancreatic insulitis grade. Moreover, the results are in line with those reported in human studies, thus suggesting NOD mice as a suitable model to study the impacts of environmental chemicals on T1D.
Place, publisher, year, edition, pages
Frontiers Media S.A., 2021. Vol. 12, article id 721507
Keywords [en]
NOD mice, PFUnDA, exposure, lipidomics, type 1 diabetes
National Category
Occupational Health and Environmental Health
Identifiers
URN: urn:nbn:se:oru:diva-95056DOI: 10.3389/fgene.2021.721507ISI: 000717296400001PubMedID: 34646301Scopus ID: 2-s2.0-85116891337OAI: oai:DiVA.org:oru-95056DiVA, id: diva2:1603719
Funder
Swedish Research Council, 2016-05176 020-03,674Swedish Research Council Formas, 2019-00869Academy of Finland, 333981The Research Council of Norway, 213060
Note
Funding agency:
Norwegian Institute of Public Health
2021-10-182021-10-182024-12-19Bibliographically approved