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.
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.
Chemosphere. 2018 Nov;210:607-614. doi: 10.1016/j.chemosphere.2018.07.066. Epub 2018 Jul 17.
Influences on lipid metabolism and multi-generational obesogenic effects raised new concerns on lipophilic pollutants (e.g., lindane). Yet, the mechanisms remained unanswered. The present study exposed Caenorhabditis elegans to lindane for 4 consecutive generations (F0 to F3) at 1.0 ng/L, and measured effects in the directly exposed generations (F0 to F3), indirectly exposed ones (T1 and T1') and un-exposed ones (T3 and T3'). Lindane stimulated fat storages in all generations. At the biochemical level, lindane stimulated both acetyl-CoA carboxylase (ACC) and carnitine palmitoyl-transferases (CPT) in F0, T1 and T2, while inhibited them in F3, T1' and T3', demonstrating the balance between fatty acid synthesis and its depletion toward fat accumulation over generations. Moreover, lindane caused different effects on insulin among generations. It inhibited insulin in F0 and F3 and exhibited consistent effects on the expression changes of daf-2, sgk-1 and daf-16 genes in insulin-like signal pathway. Lindane also inhibited insulin in T1 and T3 but exhibited consistent effects on the expression changes of daf-2, akt-1 and daf-16. Different roles of sgk-1 and akt-1 indicated the response strategies from tolerance (F0 and F3) to avoidance (T1 and T3). Lindane stimulated insulin in T1' and T3' and exhibited consistent effects on expression changes of daf-2, sgk-1 and daf-16 genes that were similar in F0 and F3.
脂代谢和多代肥胖效应的影响引发了人们对亲脂性污染物（如林丹）的新关注。然而，其机制仍未得到解答。本研究在 1.0ng/L 的林丹浓度下，连续暴露 4 代秀丽隐杆线虫（F0 至 F3），并测量了直接暴露（F0 至 F3）、间接暴露（T1 和 T1'）和未暴露（T3 和 T3'）世代的影响。林丹刺激了所有世代的脂肪储存。在生化水平上，林丹在 F0、T1 和 T2 中刺激了乙酰辅酶 A 羧化酶（ACC）和肉碱棕榈酰转移酶（CPT），而在 F3、T1'和 T3'中抑制了它们，这表明了脂肪酸合成与积累之间的平衡随着世代的推移而变化。此外，林丹对不同世代的胰岛素产生不同的影响。它抑制了 F0 和 F3 中的胰岛素，并在胰岛素样信号通路中表现出对 daf-2、sgk-1 和 daf-16 基因表达变化的一致影响。林丹还抑制了 T1 和 T3 中的胰岛素，但对 daf-2、akt-1 和 daf-16 基因的表达变化有一致的影响。sgk-1 和 akt-1 的不同作用表明了从耐受（F0 和 F3）到回避（T1 和 T3）的反应策略。林丹刺激了 T1'和 T3'中的胰岛素，并表现出对 daf-2、sgk-1 和 daf-16 基因表达变化的一致影响，这与 F0 和 F3 中的变化相似。
