Lipin-1 influences macrophage mitochondrial dynamics for improved disease resolution.

 

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B664
Abstract ID: 5540

Presenting Author:
Oluwakemi O Igiehon , Graduate Research Assistant at LSU Hlth., Shreveport

Abstract:

During inflammation, macrophages are pivotal in restoring tissue homeostasis. To resolve inflammation M2 macrophages remove apoptotic cells by efferocytosis and increase β-oxidation, oxidative phosphorylation, and channel remnant free fatty acids into triglycerides and ceramides to protect against lipotoxicity. Mitochondria regulate this lipid movement. Lipin-1 is a phosphohydrolase and has transcriptional coregulatory activity that regulates lipid metabolism. Macrophage lipin-1 promotes β-oxidation and reduces ceramide synthesis to allow for efferocytosis. How lipin-1 regulates lipid metabolism in M2 macrophages is unknown. Mitochondrial dynamics: fusion and fission, have been reported to regulate mitochondrial metabolism. Elongated mitochondria have been shown to associate with lipid droplets, facilitating lipid synthesis. Conversely, fragmented mitochondria have increased β-oxidation capacity. We hypothesized that lipin-1 regulates mitochondrial dynamics for improved β-oxidation and oxidative phosphorylation to promote pro-resolving macrophage function. We quantified mitochondria bioenergetics and mitochondria dynamics.  We observed that IL-4 treated lipin-1mKO BMDMs have longer mitochondria, suggesting a defect in mitochondrial fission. Also, mitochondrial fission protein, DRP1, and proteins of the electron transport chain are significantly reduced in the absence of lipin-1. Together, suggesting that macrophage lipin-1 influences mitochondrial dynamics for efferocytosis.