RRC ID 73523
Author Shintani T, Suzuki R, Takeuchi Y, Shirasawa T, Noda M.
Title Deletion or inhibition of PTPRO prevents ectopic fat accumulation and induces healthy obesity with markedly reduced systemic inflammation.
Journal Life Sci
Abstract AIMS:Chronic inflammation plays crucial roles in obesity-induced metabolic diseases. Protein tyrosine phosphatase receptor type O (PTPRO) is a member of the R3 subfamily of receptor-like protein tyrosine phosphatases. We previously suggested a role for PTPRO in the inactivation of the insulin receptor. The present study aimed to elucidate the involvement of PTPRO in the control of glucose and lipid metabolism as well as in obesity-induced systemic inflammation.
MATERIALS AND METHODS:Lipid accumulation in adipose tissue and the liver, the expression of inflammatory cytokines, and insulin resistance associated with systemic inflammation were investigated in hyper-obese Ptpro-KO mice by feeding a high-fat/high-sucrose diet (HFHSD). The effects of the administration of AKB9778, a specific inhibitor of PTPRO, to ob/ob mice and cultured 3T3-L1 preadipocyte cells were also examined.
KEY FINDINGS:Ptpro was highly expressed in visceral white adipose tissue and macrophages. Ptpro-KO mice fed HFHSD were hyper-obese, but did not have ectopic fat accumulation in the liver, dysfunctional lipid and glucose homeostasis, systemic inflammation, or insulin resistance. The administration of AKB9778 reproduced "the healthy obese phenotypes" of Ptpro-KO mice in highly obese ob/ob mice. Furthermore, the inhibition of PTPRO promoted the growth of lipid droplets in adipocytes through an increase in the phosphorylation of Tyr(117) in vimentin.
SIGNIFICANCE:Healthy systemic conditions with the attenuation of inflammation in hyper-obese Ptpro-KO mice were associated with the expansion of adipose tissue and low activation of NF-κb. Therefore, PTPRO may be a promising target to ameliorate hepatic steatosis and metabolic dysfunction.
Volume 313
Pages 121292
Published 2023-1-15
DOI 10.1016/j.lfs.2022.121292
PII S0024-3205(22)00992-4
PMID 36535401
MeSH Adipose Tissue / metabolism Animals Diet, High-Fat / adverse effects Glucose / metabolism Inflammation / metabolism Insulin Resistance* Lipids Mice Mice, Inbred C57BL Obesity / complications Obesity / metabolism
IF 3.647
Mice RBRC01235