title: Perilipin 5, a lipid droplet-binding protein, protects heart from oxidative burden by sequestering fatty acid from excessive oxidation.
abstract: Lipid droplets (LDs) are ubiquitous organelles storing neutral lipids, including triacylglycerol (TAG) and cholesterol ester. The properties of LDs vary greatly among tissues, and LD-binding proteins, the perilipin family in particular, play critical roles in determining such diversity. Overaccumulation of TAG in LDs of non-adipose tissues may cause lipotoxicity, leading to diseases such as diabetes and cardiomyopathy. However, the physiological significance of non-adipose LDs in a normal state is poorly understood. To address this issue, we generated and characterized mice deficient in perilipin 5 (Plin5), a member of the perilipin family particularly abundant in the heart. The mutant mice lacked detectable LDs, containing significantly less TAG in the heart. Particulate structures containing another LD-binding protein, Plin2, but negative for lipid staining, remained in mutant mice hearts. LDs were recovered by perfusing the heart with an inhibitor of lipase. Cultured cardiomyocytes from Plin5-null mice more actively oxidized fatty acid than those of wild-type mice. Production of reactive oxygen species was increased in the mutant mice hearts, leading to a greater decline in heart function with age. This was, however, reduced by the administration of N-acetylcysteine, a precursor of an antioxidant, glutathione. Thus, we conclude that Plin5 is essential for maintaining LDs at detectable sizes in the heart, by antagonizing lipase(s). LDs in turn prevent excess reactive oxygen species production by sequestering fatty acid from oxidation and hence suppress oxidative burden to the heart.
authors.affiliation: Graduate School of Life Science, University of Hyogo, Kamigori, Hyogo 678-1297, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kuramoto
authors.forename: Tomoo
authors.initials: T
authors.lastname: Okamura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Tomoe Y
authors.initials: TY
authors.lastname: Nakamura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Wakabayashi
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Morinaga
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nomura
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yanase
authors.forename: Kinya
authors.initials: K
authors.lastname: Otsu
authors.forename: Nobuteru
authors.initials: N
authors.lastname: Usuda
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Matsumura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Inoue
authors.forename: Tohru
authors.initials: T
authors.lastname: Fushiki
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kojima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Fumie
authors.initials: F
authors.lastname: Sakai
authors.forename: Fumiko
authors.initials: F
authors.lastname: Hirose
authors.forename: Takashi
authors.initials: T
authors.lastname: Osumi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D016166:Free Radical Scavengers; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D017382:Reactive Oxygen Species; D014280:Triglycerides; C551268:lipid storage droplet protein 5, mouse; D008049:Lipase; D000111:Acetylcysteine