Adipose triglyceride lipase promotes prostaglandin-dependent actin remodeling by regulating substrate release from lipid droplets

Development (Cambridge, England) · 7 authors, 3 centres

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TL;DR

This preclinical study using Drosophila oogenesis demonstrates that the enzyme ATGL releases arachidonic acid from lipid droplets, which then serves as the substrate for prostaglandin synthesis by Pxt to drive actin remodeling necessary for follicle development.

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The study investigates the role of Adipose Triglyceride Lipase (ATGL) in regulating actin remodeling during Drosophila oogenesis. Using genetic analysis, lipidomics, and fluorescent arachidonic acid (AA) tracking, the authors show that loss of ATGL disrupts actin bundle formation and cortical actin integrity in stage 10B follicles. Genetic interactions and prostaglandin (PG) treatment experiments place ATGL upstream of the PG synthase Pxt in this pathway. Lipidomic analysis detects AA-containing triglycerides in ovaries, which increase when ATGL is lost. The data support a model where ATGL releases AA from lipid droplet triglycerides, providing the substrate for Pxt-dependent PG synthesis, which in turn promotes the actin dynamics required for follicle development. Limitations include the exclusive use of the Drosophila model, with no direct human data, and the authors' speculation about conservation across organisms.

STUDY TYPE

other

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preclinical research

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100% · A

ORIGINAL PAPER

PMC10281261

Adipose triglyceride lipase promotes prostaglandin-dependent actin remodeling by regulating substrate release from lipid droplets

Development (Cambridge, England)

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ABSTRACT

ABSTRACT Lipid droplets (LDs), crucial regulators of lipid metabolism, accumulate during oocyte development. However, their roles in fertility remain largely unknown. During Drosophila oogenesis, LD accumulation coincides with the actin remodeling necessary for follicle development. Loss of the LD-associated Adipose Triglyceride Lipase (ATGL) disrupts both actin bundle formation and cortical actin integrity, an unusual phenotype also seen when the prostaglandin (PG) synthase Pxt is missing. Dominant genetic interactions and PG treatment of follicles indicate that ATGL acts upstream of Pxt to regulate actin remodeling. Our data suggest that ATGL releases arachidonic acid (AA) from LDs to serve as the substrate for PG synthesis. Lipidomic analysis detects AA-containing triglycerides in ovaries, and these are increased when ATGL is lost. High levels of exogenous AA block follicle development; this is enhanced by impairing LD formation and suppressed by reducing ATGL. Together, these data support the model that AA stored in LD triglycerides is released by ATGL to drive the production of PGs, which promote the actin remodeling necessary for follicle development. We speculate that this pathway is conserved across organisms to regulate oocyte development and promote fertility.

CITATION EXPORT

Michelle S. Giedt, Jonathon M. Thomalla, Roger P. White et al.. Adipose triglyceride lipase promotes prostaglandin-dependent actin remodeling by regulating substrate release from lipid droplets. Development (Cambridge, England). (2023). https://doi.org/10.1242/dev.201516

AUTHORS

7 · 3 CENTRES

Michelle S. Giedt, Jonathon M. Thomalla, Roger P. White, Matthew R. Johnson, Zon Weng Lai, Tina L. Tootle, Michael A. Welte

1Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
2Department of Biology, University of Rochester, Rochester, NY 14627, USA
3Harvard T.H. Chan Advanced Multi-omics Platform, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA