Chronic endoplasmic reticulum (ER) stress and sustained activation of unfolded protein response (UPR) signaling contribute to the development of type 2 diabetes in obesity. UPR signaling is a complex signaling pathway, which is still being explored in many different cellular processes. Here, we demonstrate that FK506-binding protein 11 (FKBP11), which is transcriptionally regulated by XBP1s, is severely reduced in the livers of obese mice. Restoring hepatic FKBP11 expression in obese mice initiates an atypical UPR signaling pathway marked by rewiring of PERK signaling toward NRF2, away from the eIF2α-ATF4 axis of the UPR. This alteration in UPR signaling establishes glucose homeostasis without changing hepatic ER stress, food consumption, or body weight. We conclude that ER stress during obesity can be beneficially rewired to promote glucose homeostasis. These findings may uncover possible new avenues in the development of novel approaches to treat diseases marked by ER stress.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cmet.2022.06.007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis and structural modification of the natural product Ivesinol to discover novel autophagy activators.
Eur J Med Chem
December 2024
Department of Oncology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400021, China. Electronic address:
Autophagy is a lysosome-dependent cellular degradation pathway that responds to a variety of environmental and cellular stresses, which is defective in aging and age-related diseases, therefore, targeting autophagy with small-molecule activators has potential therapeutic benefits. In this study, we successfully completed the first total synthesis of Ivesinol, an identified antibacterial natural product, and efficiently constructed a library of its analogs. To measure the effect of Ivesinol analogs on autophagic activity, we performed cell imaging-based screening approach, and observed that several Ivesinol analogs exhibited potent autophagy-regulating activity.
View Article and Find Full Text PDFPupillary response to blue light as a biomarker of seasonal pattern in Major Depressive Episode: A clinical study using pupillometry.
Psychiatry Res
December 2024
Département de psychiatrie et d'addictologie, AP-HP, GHU Paris Nord, DMU Neurosciences, Hôpital Bichat - Claude Bernard, F-75018 Paris, France; Université Paris Cité, NeuroDiderot, Inserm, FHU I2-D2, F-75019 Paris, France; Centre ChronoS, GHU Paris - Psychiatrie & Neurosciences, 1 rue Cabanis, 75014 Paris, France; CNRS UPR 3212 & Strasbourg University, Institute for Cellular and Integrative Neurosciences, F-67000, Strasbourg, France. Electronic address:
Depressive disorders are characterized by disturbances in light signal processing. More specifically, an alteration of the melanopsin response is suggested. The post-illumination pupillary response (PIPR) to blue light (post-blue PIPR) is increasingly used as a marker of the activity of intrinsically photosensitive melanopsin ganglion cells (ipRGCs).
View Article and Find Full Text PDFPotential of natural drug modulation of endoplasmic reticulum stress in the treatment of myocardial injury.
J Pharm Anal
November 2024
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
Myocardial injury (MI) is a common occurrence in clinical practice caused by various factors such as ischemia, hypoxia, infection, metabolic abnormalities, and inflammation. Such damages are characterized by a reduction in myocardial function and cardiomyocyte death that can result in dangerous outcomes such as cardiac failure and arrhythmias. An endoplasmic reticulum stress (ERS)-induced unfolded protein response (UPR) is triggered by several stressors, and its intricate signaling networks are instrumental in both cell survival and death.
View Article and Find Full Text PDF[Study of the Gut Transcriptomic Response in Drosophila melanogaster with Knockdown of Gagr, Domesticated gag Gene of Errantiviruses].
Mol Biol (Mosk)
December 2024
Faculty of Biology, Moscow State University, Moscow, 119234 Russia.
As a result of molecular domestication of the gag gene of errantiviruses, the Gagr gene was formed in the genome of Drosophila melanogaster. It has previously been shown that the Gagr gene is transcribed at the highest level in gut tissues relative to other tissues, and its transcription is most effectively induced in females in response to ammonium persulfate added to the nutrient medium. In the present work, the gut transcriptome of females with knockdown of the Gagr gene was studied in all tissues under standard conditions and under stress conditions caused by ammonium persulfate.
View Article and Find Full Text PDFNRF-mediated autophagy and UPR: Exploring new avenues to overcome cancer chemo-resistance.
Eur J Pharmacol
December 2024
Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada; Academy of Silesia, Faculty of Medicine, Rolna 43, 40-555, Katowice, Poland; Research Institutes of Oncology and Hematology, Cancer Care Manitoba-University of Manitoba, Winnipeg, MB, R3E 0V9, Canada; Biology of Breathing Theme, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, R3E 0V9, Canada. Electronic address:
Article Synopsis
- Chemo-resistance is a major challenge in cancer therapy, and NRF1 and NRF2 are important in how cells handle oxidative stress, affecting tumor growth and drug resistance.
- The study examines how NRF2 functions differently in normal and cancer cells, supporting cancer survival while protecting healthy cells.
- It suggests that targeting the NRF signaling pathways could lead to new treatments that improve the effectiveness of chemotherapy against resistant tumors.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!