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Publication : HDAC6 regulates thermogenesis of brown adipocytes through activating PKA to induce UCP1 expression.

First Author  Jung S Year  2018
Journal  Biochem Biophys Res Commun Volume  503
Issue  1 Pages  285-290
PubMed ID  29890133 Mgi Jnum  J:270593
Mgi Id  MGI:6277478 Doi  10.1016/j.bbrc.2018.06.016
Citation  Jung S, et al. (2018) HDAC6 regulates thermogenesis of brown adipocytes through activating PKA to induce UCP1 expression. Biochem Biophys Res Commun 503(1):285-290
abstractText  Mitochondrial uncoupling protein 1 (UCP1) is responsible for nonshivering thermogenesis in brown adipose tissue (BAT). UCP1 increases the conductance of the inner mitochondrial membrane (IMM) for protons to make BAT mitochondria generate heat rather than ATP. HDAC6 is a cytosolic deacetylase for non-histone substrates to regulate various cellular processes, including mitochondrial quality control and dynamics. Here, we showed that the body temperature of HDAC6 knockout mice is slightly decreased in normal hosing condition. Interestingly, UCP1 was downregulated in BAT of HDAC6 knockout mice, which extensively linked mitochondrial thermogenesis. Mechanistically, we showed that cAMP-PKA signaling plays a key role in HDAC6-dependent UCP1 expression. Notably, the size of brown adipocytes and lipid droplets in HDAC6 knockout BAT is increased. Taken together, our findings suggested that HDAC6 contributes to mitochondrial thermogenesis in BAT by increasing UCP1 expression through cAMP-PKA signaling pathway.
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