ArticleiScience2021
Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity.
Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- Mitochondrial Distress Signals at the Heart-Liver Interface: Molecular Links Between MASLD and Heart Failure.International journal of molecular sciences · 2026Review
- Growth Differentiation Factor-15 in Acute Coronary Syndromes: Prognostic Value and Barriers to Clinical Implementation.International journal of molecular sciences · 2026Review
- Novel Endocrine Signaling Axis in Cardiovascular-Kidney-Metabolic Syndrome: Interactions and Therapeutic Potential of FGF21 and GDF15.Journal of cellular biochemistry · 2026Review
- GDF15 (Growth/Differentiation Factor-15) Expression in Human Adipose Tissue and in Adipocyte Cell Lines.Biomedicines · 2026Article
- Lactate as a Chemical Modification on Proteins and Metabolites.Annual review of biochemistry · 2026Review
- Gdf15 expression in thermogenic adipocytes regulates diet-induced weight gain in a sex-dependent manner.Molecular medicine (Cambridge, Mass.) · 2026Article
- Heat shock factor-1 alleviates ER-stress in Caenorhabditis elegans.Scientific reports · 2026Article
- Pleiotropic effects of GDF-15 to regulate nutritional status: perspectives from body composition to nutrition-related disorders.British journal of biomedical science · 2026Review
- GDF15 as a sentinel of metabolic integrity: a narrative review of stress signaling, multisystem pathophysiology, and therapeutic potential.Frontiers in endocrinology · 2026Review
- Immunomodulatory functions of growth differentiation factor 15 in skin aging and inflammatory dermatoses.Frontiers in immunology · 2026Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Cigarette smoke extract promotes metastasis and oxaliplatin resistance in colon adenocarcinoma through GDF15/ERBB2/AKT pathway.European journal of medical research · 2025Article
- Characterization of growth differentiation factor 15 (GDF15) as a neurotropic adipokine permeable to the brain.Scientific reports · 2025Article
- ATF4 Deletion in Brown Adipocytes Attenuates Diet-Induced Insulin Resistance in Male Mice Independently of Weight Gain.Endocrinology · 2025Article
- Neurotensin-neurotensin receptor 2 signaling in adipocytes suppresses food intake through regulating ceramide metabolism.Cell research · 2025Article
- Neurotensin signaling in fat modulates food intake.Cell research · 2025Article
- Autophagy-related 7 (ATG7) regulates food intake and liver health during asparaginase exposure.The Journal of biological chemistry · 2025Article
- Emerging Roles of GDF15 in Metabolic and Cardiovascular Diseases.Research (Washington, D.C.) · 2025Review
- UPRmt-regulated mitokines: novel strategies for myocardial injury repair.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The eIF2α phosphorylation-dependent integrated stress response (ISR) is a signaling pathway that maintains homeostasis in mammalian cells exposed to various stresses. Here, ISR activation in adipocytes improves obesity and diabetes by regulating appetite in a non-cell-autonomous manner. Adipocyte-specific ISR activation using transgenic mice decreases body weight and improves glucose tolerance and obesity induced by a high-fat diet (HFD) via preferential inhibition of HFD intake. The transcriptome analysis of ISR-activated adipose tissue reveals that growth differentiation factor 15 (GDF15) expression is induced by the ISR through the direct regulation of the transcription factors ATF4 and DDIT3. Deficiency in the GDF15 receptor GFRAL abolishes the adipocyte ISR-dependent preferential inhibition of HFD intake and the anti-obesity effects. Pharmacologically, 10(E), 12(Z)-octadecadienoic acid induces ISR-dependent GDF15 expression in adipocytes and decreases the intake of the HFD. Based on our findings the specific activation of the ISR in adipocytes controls the non-cell-autonomous regulation of appetite.
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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.