ZNF638 RNA-seq of Brown Adipose Tissue

Type 1 diabetes is defined by autoimmune mediated destruction of the insulin producing pancreatic beta cells. Brown adipose tissue exhibits beneficial effects for systemic glycemic and lipid homeostasis via its endocrine functions. However, little is known about the contribution of brown adipocytes to beta cell destiny in T1D. Here, we report that the Zinc finger protein 638, a transcriptional factor of BAT, plays a key role in T1D. In STZ induced diabetic mice, ZNF638 levels were increased in BAT and it was regulated by glucose and ChREBP. STZ treated ZNF638 BOE mice displayed increased blood glucose levels and impaired performance in glucose tolerance test, accompanied with reduced proliferation and elevated apoptosis of islet beta cells compared to control mice, whereas ZNF638 FKO mice displayed the opposite phenotypes. Mechanically, overlapped RNA seq analysis and molecular analysis revealed that ZNF638 negatively regulated retinol binding protein 4 transcription in coordination with PPAR. Besides, in vitro experiments showed that RBP4 inhibition decreased proliferation and promoted apoptosis of STZ treated beta cells. Of note, we showed that RBP4 might bring retinol to islet, which consequently transformed to all trans retinoic acid to alleviate the damages of islet beta cells of T1D in mice ARTA treatment rescued ZNF638 BOE caused deteriorated T1D phenotype in mice.