IRX3 Overexpression Enhances Ucp1 Expression In Vivo.

摘要: Objective The Iroquois homeobox 3 (IRX3) gene was recently reported to be a functional downstream target of common polymorphism in the FTO gene, which encodes an obesity-associated protein; however, role IRX3 energy expenditure remains unclear. Studies have revealed that overexpression dominant-negative form mouse hypothalamus and adipose tissue promoted by enhancing brown/browning activities. Meanwhile, we others demonstrated knockdown impaired browning program primary preadipocytes vitro. In this study, aimed further clarify effects overexpressing human (hIRX3) on brown/beige tissues vivo. Methods Brown/beige adipocyte-specific hIRX3-overexpressing mice were generated white induced both chronic cold stimulation CL316,243 injection. Body weight, fat mass, lean measured, while morphological changes expression thermogenesis-related genes analyzed. Moreover, capacity derived from assessed. RNA sequencing also employed investigate effect hIRX3 genes. Results embryonic (Rosa26 h ;Ucp1-Cre) led increased expenditure, decreased body phenotype. After acute exposure or stimulation, showed increase Ucp1 expression. Consistent with this, adult ;Ucp1-CreERT2) moderate Ex vitro experiments Ucp1-driven Cre recombinase activity upregulated adipocytes oxygen consumption rate (OCR). analyses indicated brown enhanced cell differentiation, glycolysis, gluconeogenesis. Conclusion findings, thermogenesis, reducing mass.