Getting a 'GRiP' on Hypothalamic Endoplasmic Reticulum Stress to Combat Obesity

摘要

The endoplasmic reticulum (ER) coordinates the synthesis, folding, and sorting of proteins for retention in the cell or for entry into the secretory pathway. Certain conditions (e.g., calcium dyshomeostasis, lipotoxicity, abnormally elevated protein synthesis) may result in protein misfolding and aberrant accumulation in the ER. This process, known as ER stress, activates the adaptive unfolded protein response (UPR), a conserved set of molecular pathways that leads to decreased protein synthesis and misfolding and to increased protein degradation and autophagy, overall aiming to restore cellular homeostasis (1,2). However, persistent activation of the UPR triggers cell death pathways. ER stress and the UPR thus play crucial roles in protein folding and cell survival. Several studies further indicate that they have broader functions in the regulation of cell physiology, including growth, differentiation, and cellular metabolism.