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

• Published in: Biochemical and biophysical research communications 2015-02, Vol.457 (4), p.520-525
• Main Authors: Putri, Mirasari, Syamsunarno, Mas Rizky A.A., Iso, Tatsuya, Yamaguchi, Aiko, Hanaoka, Hirofumi, Sunaga, Hiroaki, Koitabashi, Norimichi, Matsui, Hiroki, Yamazaki, Chiho, Kameo, Satomi, Tsushima, Yoshito, Yokoyama, Tomoyuki, Koyama, Hiroshi, Abumrad, Nada A., Kurabayashi, Masahiko
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ADIPOSE TISSUE; Adipose Tissue, Brown - metabolism; Animals; BLOOD; Body Temperature; Brown adipose tissue; CARBOXYLIC ACIDS; CD36; CD36 Antigens - genetics; CD36 Antigens - metabolism; Cold Temperature; ENERGY STORAGE; FASTING; Fatty acid; Fatty Acids - metabolism; FLUORINE 18; Gene Deletion; GENES; GLUCOSE; Glucose - metabolism; GLYCOGEN; HEART; HOMEOSTASIS; HYPOTHERMIA; IODINE 125; LIPOPROTEINS; Male; MEMBRANE PROTEINS; MEMBRANE TRANSPORT; MICE; Mice, Inbred C57BL; Muscle, Skeletal - metabolism; Skeletal muscle; Stress, Physiological; STRESSES; Thermogenesis; TRIGLYCERIDES; UPTAKE
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.12.124

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. •We examined the role of CD36 in thermogenesis during cold exposure.•CD36−/− mice exhibit rapid hypothermia after cold exposure during fasting.•Uptake of fatty acid and glucose is impaired in thermogenic tissues during fasting.•Storage of energy substrates is reduced in thermogenic tissues during fasting.•CD36 is important for nutrient homeostasis to survive life-threatening challenges.