ArticleOncotarget2017
Reducing Smad3/ATF4 was essential for Sirt1 inhibiting ER stress-induced apoptosis in mice brown adipose tissue.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 54 citations in OpenAlex.
- Paneth cell SIRT1 deficiency increases intestinal stress resistance by modulating the gut microbiota.EMBO reports · 2026Article
- Chaperone-mediated insertion of mitochondrial import receptor TOM70 protects against diet-induced obesity.Nature cell biology · 2025Article
- Adipocyte Mitochondria: Deciphering Energetic Functions across Fat Depots in Obesity and Type 2 Diabetes.International journal of molecular sciences · 2024Review
- Article
- Plasticity of Adipose Tissues: Interconversion among White, Brown, and Beige Fat and Its Role in Energy Homeostasis.Biomolecules · 2024Review
- ATF4 expression in thermogenic adipocytes is required for cold-induced thermogenesis in mice via FGF21-independent mechanisms.Scientific reports · 2024Article
- The Dipeptide Gly-Pro (GP), Derived fromInternational journal of molecular sciences · 2023Article
- Brown Adipose Tissue-A Translational Perspective.Endocrine reviews · 2023Review
- Insights by which TUDCA is a potential therapy against adiposity.Frontiers in endocrinology · 2023Review
- Sirtuins: Key players in obesity-associated adipose tissue remodeling.Frontiers in immunology · 2022Review
- Brown adipocyte ATF4 activation improves thermoregulation and systemic metabolism.Cell reports · 2021Article
- Endoplasmic reticulum stress as the basis of obesity and metabolic diseases: focus on adipose tissue, liver, and pancreas.European journal of nutrition · 2021Review
- Methylglyoxal-Derived Advanced Glycation End Product (AGE4)-Induced Apoptosis Leads to Mitochondrial Dysfunction and Endoplasmic Reticulum Stress through the RAGE/JNK Pathway in Kidney Cells.International journal of molecular sciences · 2021Article
- A cold-stress-inducible PERK/OGT axis controls TOM70-assisted mitochondrial protein import and cristae formation.Cell metabolism · 2021Article
- Therapeutic Role of Sirtuins Targeting Unfolded Protein Response, Coagulation, and Inflammation in Hypoxia-Induced Thrombosis.Frontiers in physiology · 2021Review
- Depot-specific UCP1 expression in human white adipose tissue and its association with obesity-related markers.International journal of obesity (2005) · 2020Article
- miR‑195 promotes LPS‑mediated intestinal epithelial cell apoptosis via targeting SIRT1/eIF2a.International journal of molecular medicine · 2020Article
- Recombinant adiponectin peptide promotes neuronal survival after intracerebral haemorrhage by suppressing mitochondrial and ATF4-CHOP apoptosis pathways in diabetic mice via Smad3 signalling inhibition.Cell proliferation · 2020Article
- Involvement of CHOP in activin A‑induced myeloma NS‑1 cell apoptosis.Oncology reports · 2019Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sirtuin 1 (Sirt1) promotes adaptive thermogenesis by controlling the acetylation status of enzymes and transcriptional factors in interscapular brown adipose tissue (iBAT). However, the effects of Sirt1 on endoplasmic reticulum (ER) stress and apoptosis of iBAT remain elusive. In this study, the mRNA levels of Sirt1 and thermogenesis genes were reduced but the genes related with ER stress were elevated in iBAT of high-fat diet (HFD)-induced obese mice. Moreover, ER stress further inhibited mRNA level of Sirt1 and triggered brown adipocyte apoptosis in vitro and in vivo. Further analysis revealed that Sirt1 overexpression alleviated ER stress-induced brown adipocyte apoptosis by inhibiting Smad3 and ATF4. In addition, Smad3 bound to ATF4 promoter region and positively transcriptional regulation of ATF4. Our data also confirmed that Sirt1 reduced early apoptotic cells and blocked the mitochondrial apoptosis pathway by directly interacting with ATF4. Furthermore, Sirt1 attenuated tunicamycin-induced cold intolerance and elevating thermogenesis by inhibiting ER stress and apoptosis in iBAT. In summary, our data collectively revealed Sirt1 reduced ER stress and apoptosis of brown adipocyte in vivo and in vitro by inhibiting Smad3/ATF4 signal. These data reveal a novel mechanism that links Sirt1 to brown adipocyte apoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.