Homeobox C4 transcription factor promotes adipose tissue thermogenesis

• DOI: 10.2337/figshare.28255007.v1
• Publication Date: 2025-01-24T17:40:17Z
• Authors: Ting Yang; Yuxuan Wang; Hang Li; Fengshou Shi; Siqi Xu; Yingting Wu; Jiaqi Xin; Yi Liu; Mengxi Jiang

<p dir="ltr">The homeobox (HOX) family has shown potential in adipose development and function, yet the specific HOX proteins fueling thermogenesis remain elusive. In this study, we uncovered novel function of HOXC4 stimulating thermogenesis. Our bioinformatic analysis indicated an enrichment <i>Hoxc4</i> co-expressed genes metabolic pathways linked polymorphisms to parameters, suggesting its involvement regulation. mouse brown tissue, expression negatively correlated with body weight positively <i>Ucp1 </i>expression. Through gain- loss-of-function experiments mice, established that is both sufficient necessary for thermogenesis, leading enhanced cold tolerance protection against diet-induced obesity insulin resistance. Human primary adipocyte models further confirmed thermogenic activation cell-autonomous. Mechanistically, collaborates cofactor NCOA1 via hexapeptide motif form a transcriptional complex at </i>promoter, thereby promoting </i>transcription These findings delineate mechanism by which drives transcription energy metabolism, offering therapeutic targets obesity-related disorders.</p>