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

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

doi:10.1242/dev.201516

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

Journal article

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

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

Development (Cambridge), Vol.150(20), dev201516

10/15/2023

DOI: 10.1242/dev.201516

PMCID: PMC10281261

PMID: 37306387

Appears in UI Libraries Support Open Access

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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 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 ATGL acts upstream of Pxt to regulate actin remodeling. Our data suggest 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 actin remodeling necessary for follicle development. We speculate this pathway is conserved across organisms to regulate oocyte development and promote fertility.

Oogenesis

Lipid droplets

Drosophila

Prostaglandin signaling

Actin cytoskeleton

UIOWA OA Agreement

Details

Title: Subtitle: Adipose triglyceride lipase promotes prostaglandin-dependent actin remodeling by regulating substrate release from lipid droplets
Creators: Michelle S Giedt - University of Iowa
Jonathon M Thomalla - University of Rochester
Roger P White - University of Rochester
Matthew R Johnson - University of Rochester
Zon Weng Lai - Harvard T.H. Chan Advanced Multi-omics Platform, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Tina L Tootle - Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Michael A Welte - University of Rochester
Resource Type: Journal article
Publication Details: Development (Cambridge), Vol.150(20), dev201516
DOI: 10.1242/dev.201516
PMID: 37306387
PMCID: PMC10281261
NLM abbreviation: Development
eISSN: 1477-9129
Publisher: The Company of Biologists
Grant note: GM116885 / NIH HHS
Language: English
Electronic publication date: 05/12/2023
Date published: 10/15/2023
Academic Unit: Anatomy and Cell Biology
Record Identifier: 9984406143502771

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