Aberrant Ca²⁺ signaling by IP₃Rs in adipocytes links inflammation to metabolic dysregulation in obesity.

ABSTRACT: Chronic metabolic inflammation is a key feature of obesity, insulin resistance, and diabetes. Here, we showed that altered regulation of the Ca²⁺ channel inositol trisphosphate receptor (IP₃R) was an adipocyte-intrinsic event involved in the emergence and propagation of inflammatory signaling and the resulting insulin resistance. Inflammation induced by cytokine exposure in vitro or by obesity in vivo led to increases in the abundance and activity of IP₃Rs and in the phosphorylation of the Ca²⁺-dependent kinase CaMKII in adipocytes in a manner dependent on the kinase JNK. In mice, adipocyte-specific loss of IP₃R1/2 protected against adipose tissue inflammation and insulin resistance, despite the mice exhibiting substantial diet-induced

SUBMITTER: Guney E 

PROVIDER: S-EPMC10130146 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature