Secretory kinase FAM20C triggers adipocyte dysfunction inciting insulin resistance and inflammation in obesity.

ABSTRACT: Obesity is a major driver of type 2 diabetes (T2D) and related metabolic disorders, characterized by chronic inflammation and adipocyte dysfunction. However, the molecular triggers initiating these processes remain poorly understood. We identify FAM20C, a serine/threonine kinase, as an early obesity-induced mediator of adipocyte dysfunction. Fam20c expression is substantially upregulated in adipocytes in response to obesity, correlating with a proinflammatory transcriptional signature. Forced expression of Fam20c in adipocytes promotes robust upregulation of proinflammatory cytokines and induces insulin resistance that is dependent on its kinase activity. Conversely, deletion of adipocyte Fam20c after established obesity and hyperglycemia improves glucose tolerance, augments insulin sensit

SUBMITTER: Gilani A 

PROVIDER: S-EPMC12721910 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature