| Popis: |
Chronic inflammation plays crucial roles in obesity-induced metabolic diseases. We herein demonstrated that mice lacking the protein tyrosine phosphatase receptor type O (PTPRO) exhibited the hyper-obese phenotype when fed a high-fat/high-sucrose diet. However, Ptpro-KO mice with hyperobesity showed the markedly small accumulation of ectopic fat in the liver, improvements in lipid and glucose homeostasis, and low-grade systemic inflammation associated with low macrophage activation. Expression of protein tyrosine phosphatase 1b (Ptp1b), an enzyme which is known to be implicated in metabolic disorders, was also suppressed in Ptpro-KO mice. The administration of AKB9778, a specific inhibitor of PTPRO, to highly obese ob/ob mice reproduced the phenotypes of Ptpro-KO mice along with the amelioration of inflammation. We revealed that an increase in the phosphorylation of Tyr(117) in vimentin, a component of intermediate filaments, by the inhibition of PTPRO promoted the growth of lipid droplets in adipocytes. The improvement in metabolic conditions with the attenuation of inflammation in Ptpro-KO mice was explained by the low activation of NFκb, a key transcription factor for inflammatory response, in adipose tissue. This is the first study to show that PTPRO is a promising target to ameliorate hepatic steatosis and metabolic disorders. |
