Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease

By G. Hotamışlıgil. Cell, 2010

2,771 citations recorded by the source corpus.

The endoplasmic reticulum (ER) is the major site in the cell for protein folding and trafficking and is central to many cellular functions. Failure of the ER's adaptive capacity results in activation of the unfolded protein response (UPR), which intersects with many different inflammatory and stress signaling pathways. These pathways are also critical in chronic metabolic diseases such as obesity, insulin resistance, and type 2 diabetes. The ER and related signaling networks are emerging as a potential site for the intersection of inflammation and metabolic disease.

Subfields: Cell Biology, Epidemiology, Surgery

View Paper: https://www.semanticscholar.org/paper/b57e9cbf12d57a7980c6f2ebd83d25dfb1ec6322

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Citations in the corpus

Redox Regulation of NLRP3 Inflammasomes: ROS as Trigger or Effector? (2015, neutral): “In general, obesity is associated with perturbations of major cellular homeostatic pathways, such as ER stress, mitochondrial dysfunction and autophagy deficiency, that are linked to ROS accumulation and oxidative stress (54).”
What We Talk About When We Talk About Fat (2014, neutral): “, and Hotamisligil, G.S. (2008). Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets.”
Autophagy and the integrated stress response (2010, positive): “…alleviating ER stress (Harding et al., 2003). eIF2a phosphorylation initiates both a general inhibition of protein translation as well as the selective translation of some stress-responsive transcripts including that of the ATF4 transcription factor and certain autophagy genes (Hotamisligil, 2010).”
Defective Hepatic Autophagy in Obesity Promotes ER Stress and Causes Insulin Resistance (2010, background): “It has been shown that nutrient and energy surplus and inflammatory milieu associated with obesity compromise the function of the ER in major metabolic cell types and lead to insulin resistance (Hotamisligil, 2010).”
Histone Methylation Dynamics and Gene Regulation Occur through the Sensing of One-Carbon Metabolism (2015, background): “Indeed, chronic diseases, including obesity, diabetes, and cancer, often stem from the inability of the organism to adapt to the demands of its nutritional load (Hotamisligil, 2010; Laplante and Sabatini, 2012).”
Beta Cell Dysfunction and Insulin Resistance (2013, background): “Oxidative stress leads to damage in organelles, particularly the mitochondria and cellular proteins, lipids, and nucleic acids (Simmons, 2007); it also initiates and contributes to both endoplasmic reticulum (ER) stress (Kaneto et al., 2005; Hotamisligil, 2010) and autophagy (Lee et al.”
mTOR signaling in growth control and disease (2012, neutral): “, and Hotamisligil, G.S. (2008). Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis.”
Stress, Inflammation, and Defense of Homeostasis (2014, background): “It is increasingly appreciated, however, that chronic inflammation can accompany many pathological states without infection or injury, such as in adipose tissue of obese humans and animals (Hotamisligil, 2010).”
Pathophysiology of placental‐derived fetal growth restriction (2018, background): “The difference in the degree of activation may have pathophysiological significance, for high levels of activation of the UPR are associated with stimulation of the release of proinflammatory cytokines, cell senescence, and even apoptosis (Figure 6).(90,91) The nuclear factor kappa-light-chain-enhan”