Defective STIM-mediated store operated Ca²⁺ entry in hepatocytes leads to metabolic dysfunction in obesity.

ABSTRACT: Defective Ca²⁺ handling is a key mechanism underlying hepatic endoplasmic reticulum (ER) dysfunction in obesity. ER Ca²⁺ level is in part monitored by the store-operated Ca²⁺ entry (SOCE) system, an adaptive mechanism that senses ER luminal Ca²⁺ concentrations through the STIM proteins and facilitates import of the ion from the extracellular space. Here, we show that hepatocytes from obese mice displayed significantly diminished SOCE as a result of impaired STIM1 translocation, which was associated with aberrant STIM1 O-GlycNAcylation. Primary hepatocytes deficient in STIM1 exhibited elevated cellular stress as well as impaired insulin action, increased glucose production and lipid droplet accumulation. Additionally, mice with acute liver deletio

SUBMITTER: Arruda AP 

PROVIDER: S-EPMC5777820 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature