Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels
Wen Liu, Ye Yin, Meijing Wang, Ting Fan, Yuyu Zhu, Lihong Shen, Shuang Peng, Jian Gao, Guoliang Deng, Xiangbao Meng, Lingdong Kong, Gen‐Sheng Feng, Wenjie Guo, Qiang Xu, Yang Sun
Abstract
Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes.
Topics & Concepts
SteatosisInsulin resistancePhosphataseEndocrinologyInternal medicineInsulinInsulin receptorBiologyChemistryCell biologyMedicinePhosphorylationProtein Tyrosine PhosphatasesEndoplasmic Reticulum Stress and Diseaseinterferon and immune responses