| First Author | Chen Z | Year | 2021 |
| Journal | Cell Rep | Volume | 37 |
| Issue | 3 | Pages | 109868 |
| PubMed ID | 34686338 | Mgi Jnum | J:328288 |
| Mgi Id | MGI:6881857 | Doi | 10.1016/j.celrep.2021.109868 |
| Citation | Chen Z, et al. (2021) Deficiency of ER Ca(2+) sensor STIM1 in AgRP neurons confers protection against dietary obesity. Cell Rep 37(3):109868 |
| abstractText | Store-operated calcium entry (SOCE) is pivotal in maintaining intracellular Ca(2+) level and cell function; however, its role in obesity development remains largely unknown. Here, we show that the stromal interaction molecule 1 (Stim1), an endoplasmic reticulum (ER) Ca(2+) sensor for SOCE, is critically involved in obesity development. Pharmacological blockade of SOCE in the brain, or disruption of Stim1 in hypothalamic agouti-related peptide (AgRP)-producing neurons (ASKO), significantly ameliorates dietary obesity and its associated metabolic disorders. Conversely, constitutive activation of Stim1 in AgRP neurons leads to an obesity-like phenotype. We show that the blockade of SOCE suppresses general translation in neuronal cells via the 2',5'-oligoadenylate synthetase 3 (Oas3)-RNase L signaling. While Oas3 overexpression in AgRP neurons protects mice against dietary obesity, deactivation of RNase L in these neurons significantly abolishes the effect of ASKO. These findings highlight an important role of Stim1 and SOCE in the development of obesity. |
