ArticleThe Journal of clinical investigation2009
The transcription factor ATF4 regulates glucose metabolism in mice through its expression in osteoblasts.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 228 citations in OpenAlex.
- The effect of exercise training on osteocalcin, adipocytokines, and insulin resistance: a systematic review and meta-analysis of randomized controlled trials.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Pooled it
- Transcription Factor ATF4 Deletion Reprograms Glucose Metabolism in Clear Cell Renal Cell Carcinoma.Cancers · 2026Article
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- ATF4 Deletion in Brown Adipocytes Attenuates Diet-Induced Insulin Resistance in Male Mice Independently of Weight Gain.Endocrinology · 2025Article
- Hepatitis B surface antigen: carcinogenesis mechanisms and clinical implications in hepatocellular carcinoma.Experimental hematology & oncology · 2025Review
- An Overview of Research Advances in Oncology Regarding the Transcription Factor ATF4.Current drug targets · 2025Review
- Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.International journal of molecular sciences · 2024Review
- The crosstalk between metabolism and translation.Cell metabolism · 2024Review
- eIF4F complex dynamics are important for the activation of the integrated stress response.Molecular cell · 2024Article
- Signal Transducer and Activator of Transcription 4-Induced Up-Regulated LINC01278 Enhances Proliferation and Invasion of Non-Small Cell Lung Cancer Cells via the MicroRNA-877-5p/Activating Transcription Factor 4 Axis.Tissue engineering and regenerative medicine · 2024Article
- Association between protein undernutrition and diabetes: Molecular implications in the reduction of insulin secretion.Reviews in endocrine & metabolic disorders · 2024Review
- Extrahepatic Vitamin K-Dependent Gla-Proteins-Potential Cardiometabolic Biomarkers.International journal of molecular sciences · 2024Review
- Article
- NOVA1 prevents overactivation of the unfolded protein response and facilitates chromatin access during human white adipogenesis.Nucleic acids research · 2023Article
- Signaling plasticity in the integrated stress response.Frontiers in cell and developmental biology · 2023Review
- The Origins, Evolution, and Future of Dietary Methionine Restriction.Annual review of nutrition · 2022Review
- SATB2: A versatile transcriptional regulator of craniofacial and skeleton development, neurogenesis and tumorigenesis, and its applications in regenerative medicine.Genes & diseases · 2022Review
- Oxygen-sensing mechanisms in development and tissue repair.Development (Cambridge, England) · 2021Review
- Mouse strain-specific polymorphic provirus functions as cis-regulatory element leading to epigenomic and transcriptomic variations.Nature communications · 2021Article
- Hop2 interacts with the transcription factor CEBPα and suppresses adipocyte differentiation.The Journal of biological chemistry · 2021Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The recent demonstration that osteoblasts have a role in controlling energy metabolism suggests that they express cell-specific regulatory genes involved in this process. Activating transcription factor 4 (ATF4) is a transcription factor that accumulates predominantly in osteoblasts, where it regulates virtually all functions linked to the maintenance of bone mass. Since Atf4-/- mice have smaller fat pads than littermate controls, we investigated whether ATF4 also influences energy metabolism. Here, we have shown, through analysis of Atf4-/- mice, that ATF4 inhibits insulin secretion and decreases insulin sensitivity in liver, fat, and muscle. Several lines of evidence indicated that this function of ATF4 occurred through its osteoblastic expression. First, insulin sensitivity is enhanced in the liver of Atf4-/- mice, but not in cultured hepatocytes from these mice. Second, mice overexpressing ATF4 in osteoblasts only [termed here alpha1(I)Collagen-Atf4 mice] displayed a decrease in insulin secretion and were insulin insensitive. Third, the alpha1(I)Collagen-Atf4 transgene corrected the energy metabolism phenotype of Atf4-/- mice. Fourth, and more definitely, mice lacking ATF4 only in osteoblasts presented the same metabolic abnormalities as Atf4-/- mice. Molecularly, ATF4 favored expression in osteoblasts of Esp, which encodes a product that decreases the bioactivity of osteocalcin, an osteoblast-specific secreted molecule that enhances secretion of and sensitivity to insulin. These results provide a transcriptional basis to the observation that osteoblasts fulfill endocrine functions and identify ATF4 as a regulator of most functions of osteoblasts.
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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.