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

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{sup −/−} 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{sup −/−} 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 {sup 125}I-BMIPP and the glucose analogue {sup 18}F-FDG revealed that uptake of FA and glucose was severely impaired in BAT and glycolytic SkM in cold-exposed CD36{sup −/−} mice. Further, induction of the genes of thermogenesis in BAT was blunted in fasted CD36{sup −/−} mice after cold exposure. These findings strongly suggest that CD36{supmore » −/−} 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. - Highlights: • We examined the role of CD36 in thermogenesis during cold exposure. • CD36{sup −/−} 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.« less
Authors:
 [1] ;  [2] ;  [1] ;  [3] ;  [1] ;  [2] ; ;  [4] ;  [5] ;  [1] ;  [5] ; ;  [6] ;  [7] ;
  1. Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan)
  2. (Japan)
  3. (Indonesia)
  4. Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan)
  5. Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan)
  6. Department of Public Health, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan)
  7. Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan)
Publication Date:
OSTI Identifier:
22458488
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 457; Journal Issue: 4; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADIPOSE TISSUE; BLOOD; CARBOXYLIC ACIDS; ENERGY STORAGE; FASTING; FLUORINE 18; GENES; GLUCOSE; GLYCOGEN; HEART; HOMEOSTASIS; HYPOTHERMIA; IODINE 125; LIPOPROTEINS; MEMBRANE PROTEINS; MEMBRANE TRANSPORT; MICE; STRESSES; TRIGLYCERIDES; UPTAKE