Angiotensin II Inhibits Adipogenic Differentiation and Promotes Mature Adipocyte Browning through the Corepressor CtBP1

Abstract

The mechanisms of angiotensin II (Ang II) on regulating adipogenic differentiation and function remain unknown. In this study, we focus on revealing the role of C-terminal-binding protein 1 (CtBP1) on Ang II-mediated adipogenic differentiation and mature adipocyte browning. Amounts of 3T3-L1 and CtBP1-KO 3T3-L1 were treated with Ang II for 24 h and then induced adipogenic differentiation, or cells were first induced differentiation and then treated with Ang II. The expressions of CtBP1 and adipogenic markers were checked by Western blot. Transcription of CtBP1 was assayed by Real-time RT-PCR. Lipid droplet formation and size were detected by Oil Red O. Mitochondrial content and reactive oxygenspecies (ROS) were detected by Mito-tracker and MitoSOX. Mitochondrial respiratory function was detected with the corresponding kits. Mitochondrial membrane potential (MMP) (∆Ψm) was assayed by JC-1. The results show that Ang II promoted CtBP1 transcription and expression via AT1 receptor during 3T3-L1 adipogenic differentiation. Ang II significantly inhibited lipid droplet formation and adipogenic markers expression in 3T3-L1 differentiation, which was blocked by CtBP1 knockout. In mature 3T3-L1, Ang II treatment increased uncoupling protein-1 (UCP-1) expression and the number of lipid droplets, and also reduced lipid droplet size and single cell lipid accumulation, which was reversed by CtBP1 knockout. In addition, Ang II treatment enhanced mitochondrial numbers, ATP production, oxygen consumption rate (OCR) and ROS generation, and reduced MMP (∆Ψm) via CtBP1 in mature 3T3-L1 adipocytes. In conclusion, this study demonstrates that CtBP1 plays a key role in the inhibitory effect of Ang II on adipogenesis. Moreover, Ang II regulates the function of mature adipocyte via CtBP1, including promoting adipocyte browning, mitochondrial respiration and ROS generation.