Reduced fatty acid use from cd36 deficiency deteriorates streptozotocin-induced diabetic cardiomyopathy in mice

Yogi Umbarawan, Ryo Kawakami, Mas Rizky A.A. Syamsunarno, Hideru Obinata, Aiko Yamaguchi, Hirofumi Hanaoka, Takako Hishiki, Noriyo Hayakawa, Norimichi Koitabashi, Hiroaki Sunaga, Hiroki Matsui, Masahiko Kurabayashi, Tatsuya Iso

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Cardiac dysfunction is induced by multifactorial mechanisms in diabetes. Deranged fatty acid (FA) utilization, known as lipotoxicity, has long been postulated as one of the upstream events in the development of diabetic cardiomyopathy. CD36, a transmembrane glycoprotein, plays a major role in FA uptake in the heart. CD36 knockout (CD36KO) hearts exhibit reduced rates of FA transport with marked enhancement of glucose use. In this study, we explore whether reduced FA use by CD36 ablation suppresses the development of streptozotocin (STZ)-induced diabetic cardiomyopathy. We found that cardiac contractile dysfunction had deteriorated 16 weeks after STZ treatment in CD36KO mice. Although accelerated glucose uptake was not reduced in CD36KO-STZ hearts, the total energy supply, estimated by the pool size in the TCA cycle, was significantly reduced. The isotopomer analysis with13 C6-glucose revealed that accelerated glycolysis, estimated by enrichment of13 C2-citrate and13 C2-malate, was markedly suppressed in CD36KO-STZ hearts. Levels of ceramides, which are cardiotoxic lipids, were not elevated in CD36KO-STZ hearts compared to wild-type-STZ ones. Furthermore, increased energy demand by transverse aortic constriction resulted in synergistic exacerbation of contractile dysfunction in CD36KO-STZ mice. These findings suggest that CD36KO-STZ hearts are energetically compromised by reduced FA use and suppressed glycolysis; therefore, the limitation of FA utilization is detrimental to cardiac energetics in this model of diabetic cardiomyopathy.

本文言語English
論文番号881
ジャーナルMetabolites
11
12
DOI
出版ステータスPublished - 2021 12月

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 分子生物学

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