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

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 pathogen...

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Main Authors: Mas Rizky A A Syamsunarno, Tatsuya Iso, Aiko Yamaguchi, Hirofumi Hanaoka, Mirasari Putri, Masaru Obokata, Hiroaki Sunaga, Norimichi Koitabashi, Hiroki Matsui, Kazuhisa Maeda, Keigo Endo, Yoshito Tsushima, Tomoyuki Yokoyama, Masahiko Kurabayashi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24603714/pdf/?tool=EBI
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author Mas Rizky A A Syamsunarno
Tatsuya Iso
Aiko Yamaguchi
Hirofumi Hanaoka
Mirasari Putri
Masaru Obokata
Hiroaki Sunaga
Norimichi Koitabashi
Hiroki Matsui
Kazuhisa Maeda
Keigo Endo
Yoshito Tsushima
Tomoyuki Yokoyama
Masahiko Kurabayashi
author_facet Mas Rizky A A Syamsunarno
Tatsuya Iso
Aiko Yamaguchi
Hirofumi Hanaoka
Mirasari Putri
Masaru Obokata
Hiroaki Sunaga
Norimichi Koitabashi
Hiroki Matsui
Kazuhisa Maeda
Keigo Endo
Yoshito Tsushima
Tomoyuki Yokoyama
Masahiko Kurabayashi
author_sort Mas Rizky A A Syamsunarno
collection DOAJ
description 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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spelling doaj.art-583669a39c824374b6570c6da0b67f532022-12-21T21:43:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0196e9082510.1371/journal.pone.0090825Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.Mas Rizky A A SyamsunarnoTatsuya IsoAiko YamaguchiHirofumi HanaokaMirasari PutriMasaru ObokataHiroaki SunagaNorimichi KoitabashiHiroki MatsuiKazuhisa MaedaKeigo EndoYoshito TsushimaTomoyuki YokoyamaMasahiko KurabayashiHypothermia 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24603714/pdf/?tool=EBI
spellingShingle Mas Rizky A A Syamsunarno
Tatsuya Iso
Aiko Yamaguchi
Hirofumi Hanaoka
Mirasari Putri
Masaru Obokata
Hiroaki Sunaga
Norimichi Koitabashi
Hiroki Matsui
Kazuhisa Maeda
Keigo Endo
Yoshito Tsushima
Tomoyuki Yokoyama
Masahiko Kurabayashi
Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
PLoS ONE
title Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
title_full Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
title_fullStr Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
title_full_unstemmed Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
title_short Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
title_sort fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24603714/pdf/?tool=EBI
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