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Sci Total Environ. 2019 Nov 4:134762. doi: 10.1016/j.scitotenv.2019.134762. [Epub ahead of print]

Multigenerational effects of perfluorooctanoic acid on lipid metabolism of Caenorhabditis elegans and its potential mechanism.

Author information

1
State Key Laboratory of Pollution Control and Resource Reuse, Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, PR China.
2
State Key Laboratory of Pollution Control and Resource Reuse, Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, PR China; Jiaxing Tongji Institute for Environment, Jiaxing, Zhejiang 314051, PR China. Electronic address: yuzhenyang3227@tongji.edu.cn.
3
Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, PR China; College of Environmental Science and Engineering, Donghua University, Shanghai 201620, PR China.

Abstract

Per-and polyfluoroalkyl substances (PFASs), especially perfluorooctanoic acid (PFOA), have been showed to induce obesogenic effects which may last over generations. However, the underlying mechanisms are not yet clear. In the present study, wild-type N2 Caenorhabditis elegans and the daf-2 mutant were exposed to PFOA for 4 consecutive generations (F0 to F3) at 1.0 ng/L. Effects on fat content and fat metabolism in the directly exposed F0 to F3 generations, the offspring of F0 (T1 to T3) and also those of F3 (T1' to T3'). Results showed that PFOA significantly stimulated the fat contents in F0 (with the percentage of the control as 184.1%), T1 (189.5%), F1 (167.3%), F2 (238.0%), T2' (193.9%) and T3' (159.4%) while inhibited them in T3 (70%). The changes of fat contents over generations were accompanied with significant changes in enzymes facilitating fatty acid synthesis (e.g., acetyl-CoA carboxylase, fatty acid synthase and desaturase, and glycerol phosphate acyltransferase) and those in fatty acid consumption (e.g., acetyl CoA synthetase, fatty acid transport protein, acyl-CoA oxidase and carnitine palmitoyl transferase). Furthermore, RNA-Seq analysis was performed on F0, F3 and T3 generations. Based on the KEGG analysis of differential genes, PFOA exposure affected lipid metabolism signaling pathways including MAPK, fatty acid degradation, TGF-β signaling pathways. Notably, PFOA exposure provoked significantly different effects in daf-2 nematodes on fat contents, lipid metabolizing enzymes and even different signaling pathways. The overall results demonstrated that the obesogenic effects of PFOA were resulted from a complex combination of various enzymes and pathways with essential involvement of insulin signaling pathway.

KEYWORDS:

Gene expression profile; Metabolic key enzyme; Multigenerational effect; Obesogenic effect; PFOA

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