PMID- 34090141 OWN - NLM STAT- MEDLINE DCOM- 20211025 LR - 20220716 IS - 1618-131X (Electronic) IS - 1438-4639 (Print) IS - 1438-4639 (Linking) VI - 235 DP - 2021 Jun TI - Associations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) and PFAS mixtures with adipokines in midlife women. PG - 113777 LID - S1438-4639(21)00092-4 [pii] LID - 10.1016/j.ijheh.2021.113777 [doi] AB - BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure have been associated with obesity and related comorbidities, possibly through disrupting signaling pathways of adipokines. Both leptin and adiponectin can modulate metabolic processes. However, the effects of PFAS on adipokines are not well understood. OBJECTIVE: We determined if serum PFAS concentrations were associated with adipokine profiles in midlife women. METHODS: We examined 1245 women aged 45-56 years from the Study of Women's Health Across the Nation. Concentrations of 11 PFAS were quantified in baseline serum samples collected in 1999-2000. Linear and branched perfluorooctane sulfonic acid isomers (n-PFOS and Sm-PFOS) and their sum (PFOS), linear perfluorooctanoic acid (n-PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA), and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (EtFOSAA) with detection frequencies >60% were included in the analysis. Adipokines including leptin, soluble leptin receptor (sOB-R), free leptin index (FLI, the ratio of leptin to sOB-R), total and high molecular weight (HMW) adiponectin were assessed in 2002-2003. We utilized multivariable linear regressions and Bayesian kernel machine regression (BKMR) to assess individual and overall joint effects of PFAS on adipokines with adjustment for age, race/ethnicity, study site, education, smoking status, physical activity, menopausal status, and waist circumference. RESULTS: A doubling of PFAS concentrations was associated with 7.8% (95% CI: 2.5%, 13.4%) higher FLI for PFOS, 9.4% (95% CI: 3.7%, 15.3%) for n-PFOA, 5.5% (95% CI: 2.2%, 9.0%) for EtFOSAA and 7.4% (95% CI: 2.8%, 12.2%) for MeFOSAA. Similar associations were found for leptin. Only EtFOSAA was associated with lower sOB-R concentrations (-1.4%, 95% CI: -2.7%, -0.1%). Results remained in women with overweight or obesity but not those with normal weight or underweight. No statistically significant associations were observed with total or HMW adiponectin, except for PFNA with total and HMW adiponectin observed in women with normal weight or underweight. In BKMR analysis, women with PFAS concentrations at the median and the 90th percentile had 30.9% (95% CI: 15.6%, 48.3%) and 52.1% (95% CI: 27.9%, 81.0%) higher FLI, respectively, compared with those with concentrations fixed at the 10th percentile. CONCLUSION: Some PFAS may alter circulating levels of leptin. Understanding associations between PFAS and adipokines may help elucidate whether PFAS can influence obesity and metabolic disease. CI - Copyright (c) 2021 Elsevier GmbH. All rights reserved. FAU - Ding, Ning AU - Ding N AD - Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA. FAU - Karvonen-Gutierrez, Carrie A AU - Karvonen-Gutierrez CA AD - Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA. FAU - Herman, William H AU - Herman WH AD - Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. FAU - Calafat, Antonia M AU - Calafat AM AD - Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA. FAU - Mukherjee, Bhramar AU - Mukherjee B AD - Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA. FAU - Park, Sung Kyun AU - Park SK AD - Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA; Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA. Electronic address: sungkyun@umich.edu. LA - eng GR - T42 OH008455/OH/NIOSH CDC HHS/United States GR - P30 DK092926/DK/NIDDK NIH HHS/United States GR - U01 AG012554/AG/NIA NIH HHS/United States GR - P30 AG024824/AG/NIA NIH HHS/United States GR - T42OH008455/ACL/ACL HHS/United States GR - P30 ES017885/ES/NIEHS NIH HHS/United States GR - U01 AG012535/AG/NIA NIH HHS/United States GR - U01 AG012553/AG/NIA NIH HHS/United States GR - U01 NR004061/NR/NINR NIH HHS/United States GR - U01 AG012539/AG/NIA NIH HHS/United States GR - R01 ES026578/ES/NIEHS NIH HHS/United States GR - U01 AG012546/AG/NIA NIH HHS/United States GR - U19 AG063720/AG/NIA NIH HHS/United States GR - U01 AG012495/AG/NIA NIH HHS/United States GR - P30 DK020572/DK/NIDDK NIH HHS/United States GR - U01 AG012505/AG/NIA NIH HHS/United States GR - U01 AG012531/AG/NIA NIH HHS/United States GR - R01 ES026964/ES/NIEHS NIH HHS/United States GR - U01 AG017719/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20210602 PL - Germany TA - Int J Hyg Environ Health JT - International journal of hygiene and environmental health JID - 100898843 RN - 0 (Adipokines) RN - 0 (Alkanesulfonic Acids) RN - 0 (Environmental Pollutants) RN - 0 (Fluorocarbons) SB - IM MH - Adipokines MH - *Alkanesulfonic Acids MH - Bayes Theorem MH - *Environmental Pollutants MH - Female MH - *Fluorocarbons MH - Humans MH - Women's Health PMC - PMC8207532 MID - NIHMS1709051 OTO - NOTNLM OT - Adipokines OT - Adiponectin OT - Leptin OT - Metabolic disorders OT - Perfluoroalkyl and polyfluoroalkyl substances (PFAS) COIS- Disclosure: The authors declare no competing financial interest. EDAT- 2021/06/06 06:00 MHDA- 2021/10/26 06:00 PMCR- 2022/06/02 CRDT- 2021/06/05 20:23 PHST- 2021/03/04 00:00 [received] PHST- 2021/05/11 00:00 [revised] PHST- 2021/05/21 00:00 [accepted] PHST- 2021/06/06 06:00 [pubmed] PHST- 2021/10/26 06:00 [medline] PHST- 2021/06/05 20:23 [entrez] PHST- 2022/06/02 00:00 [pmc-release] AID - S1438-4639(21)00092-4 [pii] AID - 10.1016/j.ijheh.2021.113777 [doi] PST - ppublish SO - Int J Hyg Environ Health. 2021 Jun;235:113777. doi: 10.1016/j.ijheh.2021.113777. Epub 2021 Jun 2.