HDAC6 regulates thermogenesis of brown adipocytes through activating PKA to induce UCP1 expression
- Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon, 305-764 (Korea, Republic of)
Highlights: • HDAC6 regulates thermogenesis of brown adipose tissue. • cAMP-PKA signaling is responsible for HDAC6-dependent thermogenic regulation to control UCP1 expression. • HDAC6-dependent regulation of UCP1 affects lipid metabolism in brown adipose tissue. 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.
- OSTI ID:
- 23105708
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 503, Issue 1; Other Information: Copyright (c) 2018 Published by Elsevier Inc.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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