Integration of metabolomics and transcriptomics identifies pathways involved in arginine vasopressin-mediated brown adipose tissue thermogenesis and glucose tolerance improvement in type 2 diabetes mice

Type 2 diabetes (T2D), a global epidemic, is a metabolic disease often accompanied by impaired glucose tolerance and insulin resistance. Arginine vasopressin (AVP), a key neuroendocrine hormone regulating fluid balance and vascular tone, has attracted increasing attention for its association with metabolic disorders, particularly T2D. Concurrently, brown adipose tissue (BAT) has emerged as an important peripheral target for mitigating T2D; however, data on the role of AVP in improving glucose tolerance via enhancement of BAT thermogenesis remain limited. Moreover, no combined multi-omics studies have investigated the associated metabolic pathways and mechanisms. This study aimed to examine the therapeutic effect of AVP on glucose intolerance through BAT activation and to explore the related pathways using multi-omics approach. We used db/db mice, a classic T2D model, to induce impaired glucose tolerance and insulin resistance. During AVP administration, mice had ad libitum access to chow and water. Our results demonstrated that AVP enhanced BAT thermogenesis and improved glucose tolerance in T2D mice. Metabolomic and transcriptomic analyses revealed that AVP modulated inositol phosphate metabolism, the pentose phosphate pathway, and glycolysis/gluconeogenesis, alleviating glucose tolerance impairment through BAT thermogenesis via inflammatory and insulin secretion pathways. This study provides valuable insights into the effect of AVP on glucose tolerance and highlights its potential as a targeted therapeutic strategy for T2D.