Lipolysis and lipophagy play individual and interactive roles in regulating triacylglycerol and cholesterol homeostasis and mitochondrial form in zebrafish

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dc.contributor.authorSi-Lan Han
dc.contributor.authorYu-Cheng Qian
dc.contributor.authorSamwel Mchele Limbu
dc.contributor.authorJing Wang
dc.contributor.authorLi-Qiao Chen
dc.contributor.authorMei-Ling Zhang
dc.contributor.authorZhen-Yu Du
dc.date.accessioned2021-06-10T20:19:26Z
dc.date.available2021-06-10T20:19:26Z
dc.date.issued2021-06-08
dc.description.abstractNeutral lipases-mediated lipolysis and acid lipases-moderated lipophagy are two main processes for degradation of lipid droplets (LDs). However, the individual and interactive roles of these metabolic pathways are not well known across vertebrates. This study explored the roles of lipolysis and lipophagy from the aspect of neutral and acid lipases in zebrafish. We established zebrafish strains deficient in either adipose triglyceride lipase (atgl−/−; AKO fish) or lysosomal acid lipase (lal−/−; LKO fish) respectively, and then inhibited lipolysis in the LKO fish and lipophagy in the AKO fish by feeding diets supplemented with the corresponding inhibitors Atglistatin and 3-Methyladenine, respectively. Both the AKO and LKO fish showed reduced growth, swimming activity, and oxygen consumption. The AKO fish did not show phenotypes in adipose tissue, but mainly accumulated triacylglycerol (TAG) in liver, also, they had large LDs in the hepatocytes, and did not stimulate lipophagy as a compensation response but maintained basal lipophagy. The LKO fish reduced total lipid accumulation in the body but had high cholesterol content in liver; also, they accumulated small LDs in the hepatocytes, and showed increased lipolysis, especially Atgl expression, as a compensatory mechanism. Simultaneous inhibition of lipolysis and lipophagy in zebrafish resulted in severe liver damage, with the potential to trigger mitophagy. Overall, our study illustrates that lipolysis and lipophagy perform individual and interactive roles in maintaining homeostasis of TAG and cholesterol metabolism. Furthermore, the interactive roles of lipolysis and lipophagy may be essential in regulating the functions and form of mitochondria.en_US
dc.description.sponsorshipThe National Natural Science Fund of China (31830102) and Program of Shanghai Academic Research Leader (19XD1421200).en_US
dc.identifier.citationLipolysis and lipophagy play individual and interactive roles in regulating triacylglycerol and cholesterol homeostasis and mitochondrial form in zebrafish. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 158988. https://doi.org/10.1016/j.bbalip.2021.158988.en_US
dc.identifier.doihttps://doi.org/10.1016/j.bbalip.2021.158988
dc.identifier.urihttp://hdl.handle.net/20.500.11810/5767
dc.publisherElsevieren_US
dc.subjectLipolysisen_US
dc.subjectLipophagyen_US
dc.subjectInteractionen_US
dc.subjectLipid catabolismen_US
dc.subjectMitochondriaen_US
dc.subjectZebrafishen_US
dc.titleLipolysis and lipophagy play individual and interactive roles in regulating triacylglycerol and cholesterol homeostasis and mitochondrial form in zebrafishen_US
dc.typeJournal Article, Peer Revieweden_US
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