Perilipin 5, a lipid droplet-binding protein, protects heart from oxidative burden by sequestering fatty acid from excessive oxidation

Kenta Kuramoto, Tomoo Okamura, Tomohiro Yamaguchi, Tomoe Y. Nakamura, Shigeo Wakabayashi, Hidetaka Morinaga, Masatoshi Nomura, Toshihiko Yanase, Kinya Otsu, Nobuteru Usuda, Shigenobu Matsumura, Kazuo Inoue, Tohru Fushiki, Yumiko Kojima, Takeshi Hashimoto, Fumie Sakai, Fumiko Hirose, Takashi Osumi

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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 TAGin 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.

Original languageEnglish
Pages (from-to)23852-23863
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number28
DOIs
Publication statusPublished - Jul 6 2012

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kuramoto, K., Okamura, T., Yamaguchi, T., Nakamura, T. Y., Wakabayashi, S., Morinaga, H., ... Osumi, T. (2012). Perilipin 5, a lipid droplet-binding protein, protects heart from oxidative burden by sequestering fatty acid from excessive oxidation. Journal of Biological Chemistry, 287(28), 23852-23863. https://doi.org/10.1074/jbc.M111.328708