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.
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.
Sci Total Environ. 2020 Feb 10;703:134762. doi: 10.1016/j.scitotenv.2019.134762. Epub 2019 Nov 4.
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.
全氟和多氟烷基物质（PFASs），特别是全氟辛酸（PFOA），已被证明具有致肥胖作用，这种作用可能持续几代人。然而，其潜在机制尚不清楚。在本研究中，野生型 N2 秀丽隐杆线虫和 daf-2 突变体在 1.0ng/L 的 PFOA 中连续暴露 4 代（F0 至 F3）。检测直接暴露的 F0 至 F3 代、F0 的后代（T1 至 T3）以及 F3 的后代（T1'至 T3'）中脂肪含量和脂肪代谢的变化。结果表明，PFOA 显著刺激 F0 代的脂肪含量（对照的百分比为 184.1%）、T1 代（189.5%）、F1 代（167.3%）、F2 代（238.0%）、T2'代（193.9%）和 T3'代（159.4%），而在 T3 代中抑制了它们（70%）。几代之间脂肪含量的变化伴随着促进脂肪酸合成的酶（如乙酰辅酶 A 羧化酶、脂肪酸合酶和去饱和酶以及甘油磷酸酰基转移酶）和消耗脂肪酸的酶（如乙酰辅酶 A 合成酶、脂肪酸转运蛋白、酰基辅酶 A 氧化酶和肉碱棕榈酰转移酶）的显著变化。此外，还对 F0、F3 和 T3 代进行了 RNA-Seq 分析。基于差异基因的 KEGG 分析，PFOA 暴露影响了包括 MAPK、脂肪酸降解和 TGF-β 信号通路在内的脂质代谢信号通路。值得注意的是，PFOA 暴露在 daf-2 线虫中对脂肪含量、脂质代谢酶甚至不同的信号通路产生了显著不同的影响。总体结果表明，PFOA 的致肥胖作用是由各种酶和途径的复杂组合引起的，胰岛素信号通路是必不可少的。
