CD36 is indispensable for thermogenesis under conditions of fasting and cold stress

Mirasari Putri, Mas Rizky A.A. Syamsunarno, Tatsuya Iso, Aiko Yamaguchi, Hirofumi Hanaoka, Hiroaki Sunaga, Norimichi Koitabashi, Hiroki Matsui, Chiho Yamazaki, Satomi Kameo, Yoshito Tsushima, Tomoyuki Yokoyama, Hiroshi Koyama, Nada A. Abumrad, Masahiko Kurabayashi

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Hypothermia can occur during fasting when thermoregulatory mechanisms, involving fatty acid (FA) utilization, are disturbed. CD36/FA translocase is a membrane protein which facilitates membrane transport of long-chain FA in the FA consuming heart, skeletal muscle (SkM) and adipose tissues. It also accelerates uptake of triglyceride-rich lipoprotein by brown adipose tissue (BAT) in a cold environment. In mice deficient for CD36 (CD36-/- mice), FA uptake is markedly reduced with a compensatory increase in glucose uptake in the heart and SkM, resulting in lower levels of blood glucose especially during fasting. However, the role of CD36 in thermogenic activity during fasting remains to be determined. In fasted CD36-/- mice, body temperature drastically decreased shortly after cold exposure. The hypothermia was accompanied by a marked reduction in blood glucose and in stores of triacylglycerols in BAT and of glycogen in glycolytic SkM. Biodistribution analysis using the FA analogue 125I-BMIPP and the glucose analogue 18F-FDG revealed that uptake of FA and glucose was severely impaired in BAT and glycolytic SkM in cold-exposed CD36-/- mice. Further, induction of the genes of thermogenesis in BAT was blunted in fasted CD36-/- mice after cold exposure. These findings strongly suggest that CD36-/- mice exhibit pronounced hypothermia after fasting due to depletion of energy storage in BAT and glycolytic SkM and to reduced supply of energy substrates to these tissues. Our study underscores the importance of CD36 for nutrient homeostasis to survive potentially life-threatening challenges, such as cold and starvation.

Original languageEnglish
Pages (from-to)520-525
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume457
Issue number4
DOIs
StatePublished - Feb 20 2015

Keywords

  • Brown adipose tissue
  • CD36
  • Fatty acid
  • Hypothermia
  • Skeletal muscle

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