Perilipin2 depletion causes lipid droplet enlargement in the ovarian corpus luteum in mice

Abstract

Lipid droplets (LDs) are endoplasmic reticulum-derived organelles that store neutral lipids (mostly triglycerides and cholesterol esters) within a phospholipid monolayer and appear in most eukaryotic cells. Perilipins (PLINs, comprising PLIN1–5) are abundant LD-associated proteins with highly variable expression levels among tissues. Although PLINs are expressed in the mammalian ovaries, little is known about their subcellular localization and physiological functions. In this study, we investigated the localization of PLIN1–3 and their relationship with LD synthesis using mCherry-HPos reporter mice, thereby enabling the visualization of LD biogenesis in vivo. PLIN2 and PLIN3 were localized as puncta in granulosa cells with low levels of LD synthesis in developing follicles. This localization pattern was quite different from that of PLIN1, which was mainly localized in the theca and interstitial cells with high levels of LD synthesis. In the corpus luteum, where LD synthesis is highly induced, PLIN2 and PLIN3 are abundant in the particulate structures, whereas PLIN1 is poorly distributed. We also generated global Plin2-deficient mice using the CRSPR/Cas9 system and demonstrated that the lack of PLIN2 did not alter the distribution of PLIN1 and PLIN3 but unexpectedly induced LD enlargement in the corpus luteum. Collectively, our results suggest that the localization of PLIN1–3 is spatiotemporally regulated and that PLIN2 deficiency influences LD mobilization in the corpus luteum within the ovaries.

Keywords

• lipid droplet
• mouse
• ovary
• perilipin