Si-Lan HanYan LiuSamwel Mchele LimbuLi-Qiao ChenMei-Ling ZhangZhen-Yu Du2021-04-182021-04-182021-02Si-Lan Han, Yan Liu, Samwel M. Limbu, Li-Qiao Chen, Mei-Ling Zhang and Zhen-Yu Du (2020). The reduction of lipid-sourced energy production caused by ATGL inhibition cannot be compensated by activation of HSL, autophagy, and utilization of other nutrients in fish. Fish Physiology and Biochemistry, 47: 173–188. https://doi.org/10.1007/s10695-020-00904-7.http://hdl.handle.net/20.500.11810/5619The adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL)–mediated lipolysis play important roles in lipid catabolism. ATGL is considered the central rate-limiting enzyme in the mobilization of fatty acids in mammals. Currently, severe fat accumulation has been commonly detected in farmed fish globally. However, the ATGL-mediated lipolysis and the potential synergy among ATGL, HSL, and autophagy, which is another way for lipid breakdown, have not been intensively understood in fish. In the present study, we added Atglistatin as an ATGL-specific inhibitor into the zebrafish diet and fed to the fish for 5 weeks. The results showed that the Atglistatin-treated fish exhibited severe fat deposition, reduced oxygen consumption, and fatty acid β-oxidation, accompanied with increased oxidative stress and inflammation. Furthermore, the Atglistatin-treated fish elevated total and phosphorylation protein expressions of HSL. However, the free fatty acids and lipase activities in organs were still systemically reduced in the Atglistatin-treated fish, and the autophagy marker LC3 was also decreased in the liver. On the other hand, glycogenolysis was stimulated but blood glucose was higher in the Atglistatin-treated fish. The transcriptomic analysis also provided the hint that the protein turnover efficiency in Atglistatin-treated fish was likely to be accelerated, but the protein content in whole fish was not affected. Taken together, ATGL plays crucial roles in energy homeostasis such that its inhibition causes loss of lipid-sourced energy production, which cannot be compensated by activation of HSL, autophagy, and utilization of other nutrients.ATGL; Metabolism; Lipolysis; Autophagy;. Energy homeostasis; ZebrafishJournal Article, Peer Reviewedhttps://doi.org/10.1007/s10695-020-00904-7