Agpat4/Lpaat delta deficiency highlights the molecular heterogeneity of epididymal and perirenal white adipose depots
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Date
2017-10-01
Authors
Mardian, Emily B.
Bradley, Ryan M.
Henao, Juan J. Aristizabal
Marvyn, Phillip M.
Moes, Katherine A.
Bombardier, Eric
Tupling, A. Russell
Stark, Ken
Duncan, Robin E.
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Biochemistry and Molecular Biology
Abstract
Acylglycerophosphate acyltransferase 4 (AGPAT4)/lysophosphatidic acid acyltransferase delta catalyzes the formation of phosphatidic acid (PA), a precursor of triacylglycerol (TAG). We investigated the effect of Agpat4 gene ablation on white adipose tissue (WAT) after finding consistent expression across depots. Epididymal WAT mass was 40% larger in male Agpat4(-/-) mice than wild-type littermates, but unchanged in perirenal, retroperitoneal, and inguinal WAT and subscapular brown adipose tissue. Metabolic changes were identified in epididymal WAT that were not evident in perirenal WAT, which was analyzed for comparison. The total epididymal TAG content doubled, increasing adipocyte cell size without changing markers of differentiation. Enzymes involved in de novo lipogenesis and complex lipid synthesis downstream of phosphatidic acid production were also unchanged. However, total epididymal TAG hydrolase activity was reduced, and there were significant decreases in total ATGL and reduced phosphorylation of hormone-sensitive lipase at the S563 and S660 PKA-activation sites. Analysis of Agpats 1, 2, 3, and 5, as well as Gpats 1, 2, 3, and 4, demonstrated compensatory upregulation in perirenal WAT that did not occur in epididymal WAT. Our findings therefore indicate depot-specific differences in the redundancy of Agpat4 and highlight the molecular and metabolic heterogeneity of individual visceral depots.
Description
This research was originally published in Journal of Lipid Research. Mardian, E. B., Bradley, R. M., Aristizabal Henao, J. J., Marvyn, P. M., Moes, K. A., Bombardier, E., … Duncan, R. E.. Agpat4/Lpaatδ deficiency highlights the molecular heterogeneity of epididymal and perirenal white adipose depots. Journal of Lipid Research. 2017; 58(10), 2037–2050 © the American Society for Biochemistry and Molecular Biology.
Keywords
Acylglycerophosphate Acyltransferase 4, Adipose Tissue, Lipid Biochemistry, Lipolysis And Fatty Acid Metabolism, Phospholipids/Phosphatidic Acid, Triglycerides, Lipogenesis, Lysophosphatidic Acid Acyltransferase