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Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.

Authors: Syamsunarno, Mas Rizky A A  Iso, Tatsuya  Yamaguchi, Aiko  Hanaoka, Hirofumi  Putri, Mirasari  Obokata, Masaru  Sunaga, Hiroaki  Koitabashi, Norimichi  Matsui, Hiroki  Maeda, Kazuhisa  Endo, Keigo  Tsushima, Yoshito  Yokoyama, Tomoyuki  Kurabayashi, Masahiko 
Citation: Syamsunarno MR, etal., PLoS One. 2014 Mar 6;9(6):e90825. doi: 10.1371/journal.pone.0090825. eCollection 2014.
Pubmed: (View Article at PubMed) PMID:24603714
DOI: Full-text: DOI:10.1371/journal.pone.0090825

Hypothermia is rapidly induced during cold exposure when thermoregulatory mechanisms, including fatty acid (FA) utilization, are disturbed. FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipose tissues and macrophages, have been identified as key molecules in the pathogenesis of overnutrition-related diseases, such as insulin resistance and atherosclerosis. We have recently shown that FABP4/5 are prominently expressed in capillary endothelial cells in the heart and skeletal muscle and play a crucial role in FA utilization in these tissues. However, the role of FABP4/5 in thermogenesis remains to be determined. In this study, we showed that thermogenesis is severely impaired in mice lacking both FABP4 and FABP5 (DKO mice), as manifested shortly after cold exposure during fasting. In DKO mice, the storage of both triacylglycerol in brown adipose tissue (BAT) and glycogen in skeletal muscle (SkM) was nearly depleted after fasting, and a biodistribution analysis using 125I-BMIPP revealed that non-esterified FAs (NEFAs) are not efficiently taken up by BAT despite the robustly elevated levels of serum NEFAs. In addition to the severe hypoglycemia observed in DKO mice during fasting, cold exposure did not induce the uptake of glucose analogue 18F-FDG by BAT. These findings strongly suggest that DKO mice exhibit pronounced hypothermia after fasting due to the depletion of energy storage in BAT and SkM and the reduced supply of energy substrates to these tissues. In conclusion, FABP4/5 play an indispensable role in thermogenesis in BAT and SkM. Our study underscores the importance of FABP4/5 for overcoming life-threatening environments, such as cold and starvation.


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RGD Object Information
RGD ID: 13673822
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.