title: Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
abstract: 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.
authors.affiliation: Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Mas Rizky A A
authors.initials: MR
authors.lastname: Syamsunarno
authors.affiliation: Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Gunma, Japan; Education and Research Support Center, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Iso
authors.affiliation: Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Yamaguchi
authors.affiliation: Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hanaoka
authors.affiliation: Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Gunma, Japan; Department of Public Health, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Mirasari
authors.initials: M
authors.lastname: Putri
authors.affiliation: Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Obokata
authors.affiliation: Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sunaga
authors.affiliation: Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Norimichi
authors.initials: N
authors.lastname: Koitabashi
authors.affiliation: Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Department of Complementary and Alternative Medicine, Graduate School of Medicine, Osaka University Hospital, Osaka, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Endo
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tsushima
authors.affiliation: Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Gunma, Japan; Education and Research Support Center, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurabayashi
mesh_terms: D000222:Adaptation, Physiological; D002001:Adipose Tissue, Brown / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D058639:Cold-Shock Response; D005215:Fasting; D050556:Fatty Acid-Binding Proteins / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007657:Ketone Bodies / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal; D009363:Neoplasm Proteins / Q000502:physiology*; D009929:Organ Size; D022722:Thermogenesis; D015533:Transcriptional Activation; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; C493411:Fabp4 protein, mouse; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D007657:Ketone Bodies; D009363:Neoplasm Proteins; D014280:Triglycerides; D006003:Glycogen