Plin2 deletion increases cholesteryl ester lipid droplet content and disturbs cholesterol balance in adrenal cortex

Yuchuan Li; Prabhat Khanal; Frode Norheim; Marit Hjorth; Thomas Bjellaas; Christian A Drevon; Jarle Vaage; Alan R Kimmel; Knut Tomas Dalen

doi:10.1016/j.jlr.2021.100048

Plin2 deletion increases cholesteryl ester lipid droplet content and disturbs cholesterol balance in adrenal cortex

J Lipid Res. 2021:62:100048. doi: 10.1016/j.jlr.2021.100048. Epub 2021 Feb 11.

Authors

Yuchuan Li¹, Prabhat Khanal², Frode Norheim¹, Marit Hjorth¹, Thomas Bjellaas³, Christian A Drevon⁴, Jarle Vaage⁵, Alan R Kimmel⁶, Knut Tomas Dalen⁷

Affiliations

¹ Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
² Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; Faculty of Biosciences and Aquaculture, Nord University, Steinkjer, Norway.
³ VITAS AS, Oslo, Norway.
⁴ Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; VITAS AS, Oslo, Norway.
⁵ Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.
⁶ Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, The National Institutes of Health, Bethesda, MD, USA.
⁷ Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; The Norwegian Transgenic Center, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. Electronic address: k.t.dalen@medisin.uio.no.

Abstract

Cholesteryl esters (CEs) are the water-insoluble transport and storage form of cholesterol. Steroidogenic cells primarily store CEs in cytoplasmic lipid droplet (LD) organelles, as contrasted to the majority of mammalian cell types that predominantly store triacylglycerol (TAG) in LDs. The LD-binding Plin2 binds to both CE- and TAG-rich LDs, and although Plin2 is known to regulate degradation of TAG-rich LDs, its role for regulation of CE-rich LDs is unclear. To investigate the role of Plin2 in the regulation of CE-rich LDs, we performed histological and molecular characterization of adrenal glands from Plin2^+/+ and Plin2^-/- mice. Adrenal glands of Plin2^-/- mice had significantly enlarged organ size, increased size and numbers of CE-rich LDs in cortical cells, elevated cellular unesterified cholesterol levels, and increased expression of macrophage markers and genes facilitating reverse cholesterol transport. Despite altered LD storage, mobilization of adrenal LDs and secretion of corticosterone induced by adrenocorticotropic hormone stimulation or starvation were similar in Plin2^+/+ and Plin2^-/- mice. Plin2^-/- adrenals accumulated ceroid-like structures rich in multilamellar bodies in the adrenal cortex-medulla boundary, which increased with age, particularly in females. Finally, Plin2^-/- mice displayed unexpectedly high levels of phosphatidylglycerols, which directly paralleled the accumulation of these ceroid-like structures. Our findings demonstrate an important role of Plin2 for regulation of CE-rich LDs and cellular cholesterol balance in the adrenal cortex.

Keywords: Plin1; Plin2; Plin3; adrenal cortex; cholesterol balance; cholesteryl ester; corticosterone; lipid droplets; lysophosphatidylcholine; phosphatidylglycerol.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Adrenal Cortex* / cytology
Adrenal Cortex* / metabolism
Animals
Cholesterol Esters* / metabolism
Cholesterol* / metabolism
Female
Gene Deletion
Lipid Droplets* / metabolism
Male
Mice
Mice, Knockout
Perilipin-2* / genetics
Perilipin-2* / metabolism

Substances

Cholesterol Esters
Cholesterol
Perilipin-2
Plin2 protein, mouse