Associations between liver PFAS concentrations and plasma extracellular miRNAs in a cohort of adolescents undergoing bariatric surgery
Year: 2021
Type: conference-paper
Abstract: BACKGROUND AND AIM: Perfluoroalkyl substances (PFAS), the “forever chemicals”, accumulate mainly in the liver and have various adverse health effects. Little is known about the mechanistic pathways of PFAS toxicity, but one likely mechanism is alteration of microRNA (miRNA) profiles that regulate post-transcription gene expression. This study aimed to explore relationships between hepatic PFAS concentrations and extracellular miRNAs in adolescents with severy obesity undergoing bariatric surgery. METHODS: PFAS concentrations (PFOS, PFOA, PFHxS, PFNA, PFDA, PFUdA, PFHpA, 8:2 FTS, 6:2 FTS, and NMeFOSAA) were assessed in liver biopsy samples (LOD0.01 ng/g tissue) collected at the time of bariatric surgery from 63 participants (mean [SD] age: 16.3 [1.7] years; 73% female) of the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort. HTG EdgeSeq quantified plasma extracellular miRNAs, of which 803 had a coefficient of variation 25% among the control replicates and were used for analysis. Linear regression was performed to examine the pairwise associations between each liver PFAS concentration and each miRNA after adjusting for age, sex, race, pre-surgery weight loss, and BMI. KEGG pathway analysis was used to identify putative biological functions of PFAS-associated miRNAs. RESULTS:Median (IQR) hepatic PFAS concentrations ranged from 0.9 (0.08-0.13) ng/g liver for 6:2FTS to 6.57 (4.79-9.55) ng/g liver for PFOS. The greatest extent of associations with the expression of individual miRNAs was observed among PFOS and PFHxS, with PFOS being associated with upregulation of 9 miRNAs and PFHxS with downregulation of 15 miRNAs. Putative targets of dysregulated miRNAs associated with PFAS included pathways involved in cell cycle and cancer (e.g., TGF-beta signaling, Wnt signaling, p53 signaling, MAPK signaling), lipid metabolism (e.g., fatty acid biosynthesis, glycerophospholipid metabolism) and glucose metabolism (e.g., insulin signaling). CONCLUSIONS:Altered miRNA expression might be a mode of action of PFAS toxicity. Findings of this study offer new avenues to explore the mechanistic link between PFAS and disease. KEYWORDS: liver tissue, PFAS, extracellular miRNAs, adolescents
Source: ISEE Conference Abstracts
Authors: Nikos Stratakis, Brittney O. Baumert, David Conti, Haotian Wu, Philippe Grandjean, Flemming Nielsen, Douglas I. Walker, Damaskini Valvi, Michele A. A. La Merrill, Sandrah P. Eckel, Justin Ryder, Marc Michalsky, Mary Brandt, Stephanie Sisley, Rohit Kohli, Stavra A. Xanthakos, Thomas Inge, Todd Jenkins, Andrea Baccarelli, Rob McConnell, Leda Chatzi
Institutions: University of Southern California, Columbia University, Harvard University, University of Southern Denmark, Icahn School of Medicine at Mount Sinai, University of California, Davis, University of Minnesota, Nationwide Children's Hospital, The Ohio State University, Baylor College of Medicine, Texas Children's Hospital, Children's Hospital of Los Angeles, Cincinnati Children's Hospital Medical Center, University of Cincinnati, University of Cincinnati Medical Center, Children's Hospital Colorado
Language: English
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Open Access status: diamond
OpenAlex ID: W3194710320