ArticleNature medicine2014
Obesity- and aging-induced excess of central transforming growth factor-β potentiates diabetic development via an RNA stress response.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
What it found
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Who cites it
89 citing papers in PubMed, 143 citations in OpenAlex.
- Hypothalamic Inflammaging: A Central Driver of Type 2 Diabetes Mellitus and Metabolic Disease in Aging.Diabetes & metabolism journal · 2026Review
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- Redefining the timeline: a three-phase framework of hypothalamic microinflammation in metabolic disease.Reviews in endocrine & metabolic disorders · 2026Review
- Hypothalamic astrocytes: connecting brain and periphery in metabolic control.Reviews in endocrine & metabolic disorders · 2026Review
- Organellar insights in ageing and longevity.Nature cell biology · 2026Review
- Neurometabolic and Neuroinflammatory Consequences of Obesity: Insights into Brain Vulnerability and Imaging-Based Biomarkers.International journal of molecular sciences · 2026Review
- Maternal high-fat diet exposure is associated with altered hypothalamic microglial development and reduced early postnatal TGFβ1 signaling in male offspring.Frontiers in endocrinology · 2026Article
- Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.Molecular psychiatry · 2026Article
- Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.Research square · 2025Article
- A High-Fat Diet Increases Kidney Fibrosis Through Regulating TGF-β and PDGF-β Signaling Pathways in Normotensive and Hypertensive Rat Models.International journal of molecular sciences · 2025Article
- Recent advances in targeting obesity, with a focus on TGF-β signaling and vagus nerve innervation.Bioelectronic medicine · 2025Review
- Targeting cellular senescence in kidney diseases and aging: A focus on mesenchymal stem cells and their paracrine factors.Cell communication and signaling : CCS · 2024Review
- Correlation between lipid accumulation product and epigenetic age acceleration in American adults: a cross-sectional analysis using NHANES data.European journal of medical research · 2024Article
- The dichotomic role of cytokines in aging.Biogerontology · 2024Review
- Physiopathological Roles of White Adiposity and Gut Functions in Neuroinflammation.International journal of molecular sciences · 2024Review
- Exercise as a Therapeutic Strategy for Obesity: Central and Peripheral Mechanisms.Metabolites · 2024Review
- Adverse Events of Oral GLP-1 Receptor Agonist (Semaglutide Tablets): A Real-World Study Based on FAERS from 2019 to 2023.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2024Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Maternal Western diet programs cardiometabolic dysfunction and hypothalamic inflammation via epigenetic mechanisms predominantly in the male offspring.Molecular metabolism · 2024Article
- Review
29 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The brain, in particular the hypothalamus, plays a role in regulating glucose homeostasis; however, it remains unclear whether this organ is causally and etiologically involved in the development of diabetes. Here, we found that hypothalamic transforming growth factor-β (TGF-β) production is excessive under conditions of not only obesity but also aging, which are two general etiological factors of type 2 diabetes. Pharmacological and genetic approaches revealed that central TGF-β excess caused hyperglycemia and glucose intolerance independent of a change in body weight. Further, using cell-specific genetic analyses in vivo, we found that astrocytes and proopiomelanocortin neurons are responsible for the production and prodiabetic effect of central TGF-β, respectively. Mechanistically, TGF-β excess induced a hypothalamic RNA stress response, resulting in accelerated mRNA decay of IκBα, an inhibitor of proinflammatory nuclear factor-κB. These results reveal an atypical, mRNA metabolism-driven hypothalamic nuclear factor-κB activation, a mechanism that links obesity as well as aging to hypothalamic inflammation and ultimately to type 2 diabetes.
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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.