Blunted Expression of PPARa in Mice with FABP-4 and -5 Deficiency under Acute Cold Exposure
Abstract
Brown Adipose Tissue (BAT) is a nonshivering thermogenesis organ during cold exposure. Peroxisomal proliferator activated receptor alpha (PPARa) is the member of the nuclear hormone receptor superfamily and primarily expressed in BAT and liver. PPARa is coordinated with uncoupling protein 1 (UCP1) to regulate fatty acid metabolism in BAT. Fatty acid binding protein (FABP)-4 and-5 play role in adaptive response under fasting and cold exposure. The purpose of this study was to investigate the expression of PPARa in mice with FABP4/5 deficiency (DKO). Wildtype (WT) and DKO mice were exposed to cold for 2 hours under fed or 20 hours-fasted conditions. BAT was collected and further mRNA level of PPARa was examined using quantitative real-time PCR. As the result, PPARa gene expression in WT mice were increased 50% and 100% in fed and fasted condition respectively after cold exposure. There was no alteration in PPARa expression in BAT of DKO mice. As conclusion, The functional FABP-4 and -5 are necessary to modulate PPARa gene expression in Brown Adipose Tissue under acute cold exposure
Keywords: Acute cold exposure; FABP4; FABP5; Fasting PPARa
References
AbdelHafez, F. F.; Desai, N.; Abou-Setta, A. M.; Falcone, T.; Goldfarb, J., Slow freezing, vitrification and ultra-rapid freezing of human embryos: a systematic review and meta-analysis. Reproductive biomedicine online 2010, 20 (2), 209-22.
Haman, F.; Mantha, O. L.; Cheung, S. S.; DuCharme, M. B.; Taber, M.; Blondin, D. P.; McGarr, G. W.; Hartley, G. L.; Hynes, Z.; Basset, F. A., Oxidative fuel selection and shivering thermogenesis during a 12-and 24-h cold-survival simulation. Journal of Applied Physiology 2016, 120 (6), 640-648
(a) Bartelt, A.; Bruns, O. T.; Reimer, R.; Hohenberg, H.; Ittrich, H.; Peldschus, K.; Kaul, M. G.; Tromsdorf, U. I.; Weller, H.; Waurisch, C., Brown adipose tissue activity controls triglyceride clearance. Nature medicine 2011, 17 (2), 200-205; (b) Putri, M.; Syamsunarno, M. R.; Iso, T.; Yamaguchi, A.; Hanaoka, H.; Sunaga, H.; Koitabashi, N.; Matsui, H.; Yamazaki, C.; Kameo, S.; Tsushima, Y.; Yokoyama, T.; Koyama, H.; Abumrad, N. A.; Kurabayashi, M., CD36 is indispensable for thermogenesis under conditions of fasting and cold stress. Biochemical and biophysical research communications 2015, 457 (4), 520-5; (c) Syamsunarno, M. R.; Iso, T.; Yamaguchi, A.; Hanaoka, H.; Putri, M.; Obokata, M.; Sunaga, H.; Koitabashi, N.; Matsui, H.; Maeda, K.; Endo, K.; Tsushima, Y.; Yokoyama, T.; Kurabayashi, M., Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress. PloS one 2014, 9 (6), e90825.
Symonds, M. E., Brown adipose tissue growth and development. Scientifica 2013, 2013.
5 Power, G. G., Biology of temperature: the mammalian fetus. Journal of developmental physiology 1989, 12 (6), 295-304
(a) Kersten, S.; Seydoux, J.; Peters, J. M.; Gonzalez, F. J.; Desvergne, B.; Wahli, W., Peroxisome proliferator–activated receptor α mediates the adaptive response to fasting. The Journal of clinical investigation 1999, 103 (11), 1489-1498; (b) De Souza, A. T.; Dai, X.; Spencer, A. G.; Reppen, T.; Menzie, A.; Roesch, P. L.; He, Y.; Caguyong, M. J.; Bloomer, S.; Herweijer, H., Transcriptional and phenotypic comparisons of Ppara knockout and siRNA knockdown mice. Nucleic acids research 2006, 34 (16), 4486-4494
Iizuka, K.; Wu, W.; Horikawa, Y.; Saito, M.; Takeda, J., Feedback looping between ChREBP and PPARα in the regulation of lipid metabolism in brown adipose tissues. Endocrine journal 2013, 60 (10), 1145-1153.
Cannon, B.; Nedergaard, J. A. N., Brown Adipose Tissue: Function and Physiological Significance. Physiological Reviews 2004, 84 (1), 277-359.
Fan, W.; Evans, R., PPARs and ERRs: molecular mediators of mitochondrial metabolism. Current opinion in cell biology 2015, 33, 49-54.
Furuhashi, M., Fatty Acid-Binding Proteins, a Family of Lipid Chaperones. In Biogenesis of Fatty Acids, Lipids and Membranes, Springer: 2017; pp 1-16.
Maeda, K.; Cao, H.; Kono, K.; Gorgun, C. Z.; Furuhashi, M.; Uysal, K. T.; Cao, Q.; Atsumi, G.; Malone, H.; Krishnan, B., Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell metabolism 2005, 1 (2), 107-119.
Iso, T.; Maeda, K.; Hanaoka, H.; Suga, T.; Goto, K.; Syamsunarno, M. R.; Hishiki, T.; Nagahata, Y.; Matsui, H.; Arai, M.; Yamaguchi, A.; Abumrad, N. A.; Sano, M.; Suematsu, M.; Endo, K.; Hotamisligil, G. S.; Kurabayashi, M., Capillary endothelial fatty acid binding proteins 4 and 5 play a critical role in fatty acid uptake in heart and skeletal muscle. Arteriosclerosis, thrombosis, and vascular biology 2013, 33 (11), 2549-57.
(a) Syamsunarno, M. R.; Iso, T.; Hanaoka, H.; Yamaguchi, A.; Obokata, M.; Koitabashi, N.; Goto, K.; Hishiki, T.; Nagahata, Y.; Matsui, H.; Sano, M.; Kobayashi, M.; Kikuchi, O.; Sasaki, T.; Maeda, K.; Murakami, M.; Kitamura, T.; Suematsu, M.; Tsushima, Y.; Endo, K.; Hotamisligil, G. S.; Kurabayashi, M., A critical role of fatty acid binding protein 4 and 5 (FABP4/5) in the systemic response to fasting. PloS one 2013, 8 (11), e79386; (b) Syamsunarno, M.; Ghozali, M.; Nugraha, G. I.; Panigoro, R.; Iso, T.; Putri, M.; Kurabayashi, M., Fatty liver in fasted FABP4/5 null mice is not followed by liver function deterioration. In Advances in Biomolecular Medicine, CRC Press/Balkema: 2017; pp 109-112.