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Lipid abundance in zebrafish embryos is regulated by complementary actions of the endocannabinoid system and retinoic acid pathway

Fraher, Daniel, Ellis, Megan K., Morrison, Shona, McGee, Sean L., Ward, Alister C., Walder, Ken and Gibert, Yann 2015, Lipid abundance in zebrafish embryos is regulated by complementary actions of the endocannabinoid system and retinoic acid pathway, Endocrinology, vol. 156, no. 10, pp. 3596-3609, doi: 10.1210/EN.2015-1315.

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Title Lipid abundance in zebrafish embryos is regulated by complementary actions of the endocannabinoid system and retinoic acid pathway
Author(s) Fraher, Daniel
Ellis, Megan K.
Morrison, Shona
McGee, Sean L.
Ward, Alister C.ORCID iD for Ward, Alister C. orcid.org/0000-0001-7945-7975
Walder, Ken
Gibert, Yann
Journal name Endocrinology
Volume number 156
Issue number 10
Start page 3596
End page 3609
Total pages 14
Publisher Endocrine Society
Place of publication Bethesda, Md.
Publication date 2015
ISSN 1945-7170
Summary The endocannabinoid system (ECS) and retinoic acid (RA) signaling have been associated with influencing lipid metabolism. We hypothesized that modulation of these pathways could modify lipid abundance in developing vertebrates and that these pathways could have a combinatorial effect on lipid levels. Zebrafish embryos were exposed to chemical treatments altering the activity of the ECS and RA pathway. Embryos were stained with the neutral lipid dye Oil-Red-O (ORO) and underwent whole-mount in situ hybridization. Mouse 3T3-L1 fibroblasts were differentiated under exposure to RA modulating chemicals and subsequently stained with ORO and analyzed for gene expression by qRT-PCR. ECS activation and RA exposure increased lipid abundance and the expression of lipoprotein lipase. Additionally, RA treatment increased expression of CCAAT/enhancer binding protein alpha. Both ECS receptors and RA receptor subtypes were separately involved in modulating lipid abundance. Finally, increased ECS or RA activity ameliorated the reduced lipid abundance caused by peroxisome proliferator-activated receptor gamma (PPARγ) inhibition. Therefore, the ECS and RA pathway influence lipid abundance in zebrafish embryos and have an additive effect when treated simultaneously. Furthermore, we demonstrated that these pathways act downstream or independently of PPARγ to influence lipid levels. Our study shows for the first time that the RA and ECS pathways have additive function in lipid abundance during vertebrate development.
Language eng
DOI 10.1210/EN.2015-1315
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Endocrine Society
Persistent URL http://hdl.handle.net/10536/DRO/DU:30074636

Document type: Journal Article
Collection: School of Medicine
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Created: Thu, 23 Jul 2015, 10:41:23 EST

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