Hoxa5 increases mitochondrial apoptosis by inhibiting Akt/mTORC1/S6K1 pathway in mice white adipocytes

Abstract

Homeobox A5 (Hoxa5), a member of the Hox family, plays a important role in the regulation of proliferation and apoptosis in cancer cells. The dysregulation of the adipocyte apoptosis in vivo leads to obesity and metabolic disorders. However, the effects of Hoxa5 on adipocyte apoptosis are still unknown. In this study, palmitic acid (PA) significantly increased the mRNA level of Hoxa5 and triggered white adipocyte apoptosis in vivo and in vitro. Further analysis revealed that Hoxa5 enhanced the early and late apoptotic cells and fragmentation of genomic DNA in adipocytes from inguinal white adipose tissue (iWAT) of mice. Moreover, Hoxa5 aggravated white adipocyte apoptosis through mitochondrial pathway rather than endoplasmic reticulum stress (ERS)-induced or death receptor (DR)-mediated pathway. Our data also confirmed that Hoxa5 promoted mitochondrial apoptosis pathway by elevating the transcription activity of Bax and inhibiting the protein kinase B (Akt)/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. In summary, these findings revealed a novel mechanism that linked Hoxa5 to white adipocyte apoptosis, which provided some potential possibilities to prevent and treat obesity and some metabolic diseases.