Luo Zhili, Yu Zhenyang, Yin Daqiang
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; Jiaxing Tongji Institute for Environment, Jiaxing, Zhejiang Province, 3014051, 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; Jiaxing Tongji Institute for Environment, Jiaxing, Zhejiang Province, 3014051, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai, 200092, PR China.
Environ Pollut. 2022 Feb 1;294:118615. doi: 10.1016/j.envpol.2021.118615. Epub 2021 Dec 1.
Environmental obesogens contributed significantly to the obesity prevalence. Recently, antibiotics joined the list of environmental obesogens, while the underlying mechanisms remained to be explored. In the present study, effects of erythromycin (ERY), one widely used macrolide antibiotic, were measured on C. elegans to investigate the obesogenic mechanism. Results showed that ERY at 0.1 μg/L significantly increased the fat content by 17.4% more than the control and also stimulated triacylglycerol (TAG) levels by 25.7% more than the control. Regarding the obesogenic mechanisms, ERY provoked over-eating by stimulation on the pharyngeal pumping and reduction on the satiety quiescence percentage and duration. Such effects were resulted from stimulation on the neurotransmitters including serotonin (5-HT), dopamine (DA) and acetylcholine (ACh). The nervous responses involved the up-regulation of Gsα (e.g., ser-7, gsa-1, acy-1 and kin-2) signaling pathway and the down-regulation of TGFβ (daf-7) but not via cGMP-dependent regulations (e.g., egl-4). Moreover, ERY stimulated the activities of fatty acid synthase (FAS) and glycerol-3-phosphateacyl transferases (GPAT) that catalyze lipogenesis, while ERY inhibited those of acyl-CoA synthetase (ACS), carnitine palmitoyl transferase (CPT) and acyl-CoA oxidase (ACO) that catalyze lipolysis. The unbalance between lipogenesis and lipolysis resulted in the fat accumulation which was consistent with up-regulation on mgl-1 and mgl-3 which are the down-steam of TGFβ regulation. Such consistence supported the close connection between nervous regulation and lipid metabolism. In addition, ERY also disturbed insulin which connects lipid with glucose in metabolism.
环境致肥胖物对肥胖流行率有重大影响。最近，抗生素也被列入环境致肥胖物清单，但其潜在机制仍有待探索。在本研究中，我们检测了广泛使用的大环内酯类抗生素红霉素（ERY）对秀丽隐杆线虫的影响，以探究其致肥胖机制。结果显示，0.1μg/L的ERY使脂肪含量比对照组显著增加了17.4%，同时也使甘油三酯（TAG）水平比对照组提高了25.7%。关于致肥胖机制，ERY通过刺激咽部抽吸和降低饱腹感静止百分比及持续时间引发过度进食。这些影响是由对包括血清素（5-HT）、多巴胺（DA）和乙酰胆碱（ACh）在内的神经递质的刺激引起的。神经反应涉及Gsα（如ser-7、gsa-1、acy-1和kin-2）信号通路的上调以及TGFβ（daf-7）的下调，但不是通过cGMP依赖性调节（如egl-4）。此外，ERY刺激了催化脂肪生成的脂肪酸合酶（FAS）和甘油-3-磷酸酰基转移酶（GPAT）的活性，而ERY抑制了催化脂肪分解的酰基辅酶A合成酶（ACS）、肉碱棕榈酰转移酶（CPT）和酰基辅酶A氧化酶（ACO）的活性。脂肪生成与脂肪分解之间的失衡导致了脂肪积累，这与TGFβ调节下游的mgl-1和mgl-3的上调一致。这种一致性支持了神经调节与脂质代谢之间的紧密联系。此外，ERY还扰乱了在代谢中将脂质与葡萄糖联系起来的胰岛素。
