ER stress and inflammation crosstalk in obesity

• Published in: Medicinal research reviews Vol. 43; no. 1; pp. 5 - 30
• Main Authors: Ajoolabady, Amir, Lebeaupin, Cynthia, Wu, Ne N., Kaufman, Randal J., Ren, Jun
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2023
• Subjects: adipocytes; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - pathology; Endoplasmic Reticulum Stress; ER stress; Gene expression; Humans; Inflammation; Inflammation - pathology; insulin resistance; Obesity; Unfolded Protein Response; ER stress; inflammation; adipocytes; insulin resistance; obesity
• ISSN: 0198-6325; 1098-1128
• DOI: 10.1002/med.21921

The endoplasmic reticulum (ER) governs the proper folding of polypeptides and proteins through various chaperones and enzymes residing within the ER organelle. Perturbation in the ER folding process ensues when overwhelmed protein folding exceeds the ER handling capacity, leading to the accumulation of misfolded/unfolded proteins in the ER lumen—a state being referred to as ER stress. In turn, ER stress induces a gamut of signaling cascades, termed as the “unfolded protein response” (UPR) that reinstates the ER homeostasis through a panel of gene expression modulation. This type of UPR is usually deemed “adaptive UPR.” However, persistent or unresolved ER stress hyperactivates UPR response, which ultimately, triggers cell death and inflammatory pathways, termed as “maladaptive/terminal UPR.” A plethora of evidence indicates that crosstalks between ER stress (maladaptive UPR) and inflammation precipitate obesity pathogenesis. In this regard, the acquisition of the mechanisms linking ER stress to inflammation in obesity might unveil potential remedies to tackle this pathological condition. Herein, we aim to elucidate key mechanisms of ER stress‐induced inflammation in the context of obesity and summarize potential therapeutic strategies in the management of obesity through maneuvering ER stress and ER stress‐associated inflammation.