ArticleEndocrinology2011
Insulin/IGF-I regulation of necdin and brown adipocyte differentiation via CREB- and FoxO1-associated pathways.
Article in Endocrinology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors.The Journal of biological chemistry · 2013Trial
- Novel Transcriptomic Signatures in Fibrostenotic Crohn's Disease: Dysregulated Pathways, Promising Biomarkers, and Putative Therapeutic Targets.Inflammatory bowel diseases · 2025Article
- Hormonal Determinants of Growth and Weight Gain in the Human Fetus and Preterm Infant.Nutrients · 2023Review
- Necdin: A purposive integrator of molecular interaction networks for mammalian neuron vitality.Genes to cells : devoted to molecular & cellular mechanisms · 2021Review
- Effect of oxymatrine on liver gluconeogenesis is associated with the regulation of PEPCK and G6Pase expression and AKT phosphorylation.Biomedical reports · 2021Article
- Neuropeptide B promotes proliferation and differentiation of rat brown primary preadipocytes.FEBS open bio · 2021Article
- Review
- UniProt-Related Documents (UniReD): assisting wet lab biologists in their quest on finding novel counterparts in a protein network.NAR genomics and bioinformatics · 2020Article
- Flufenamic Acid Inhibits Adipogenic Differentiation of Mesenchymal Stem Cells by Antagonizing the PI3K/AKT Signaling Pathway.Stem cells international · 2020Article
- Transcriptional changes in the hypothalamus, pituitary, and mammary gland underlying decreased lactation performance in mice under heat stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- miR-431 inhibits adipogenic differentiation of human bone marrow-derived mesenchymal stem cells via targeting insulin receptor substance 2.Stem cell research & therapy · 2018Article
- Supra-pharmacological concentration of capsaicin stimulates brown adipogenesis through induction of endoplasmic reticulum stress.Scientific reports · 2018Article
- Metabolically Active Three-Dimensional Brown Adipose Tissue Engineered from White Adipose-Derived Stem Cells.Tissue engineering. Part A · 2017Article
- Article
- Matrix metalloproteinase 11 protects from diabesity and promotes metabolic switch.Scientific reports · 2016Article
- Disruption of insulin signaling in Myf5-expressing progenitors leads to marked paucity of brown fat but normal muscle development.Endocrinology · 2015Article
- Myocardial ischemic protection in natural mammalian hibernation.Basic research in cardiology · 2015Article
- Leptin's role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals.Endocrine reviews · 2013Review
- Lgr4/Gpr48 negatively regulates TLR2/4-associated pattern recognition and innate immunity by targeting CD14 expression.The Journal of biological chemistry · 2013Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Brown adipose tissue plays an important role in obesity, insulin resistance, and diabetes. We have previously shown that the transition from brown preadipocytes to mature adipocytes is mediated in part by insulin receptor substrate (IRS)-1 and the cell cycle regulator protein necdin. In this study, we used pharmacological inhibitors and adenoviral dominant negative constructs to demonstrate that this transition involves IRS-1 activation of Ras and ERK1/2, resulting in phosphorylation of cAMP response element-binding protein (CREB) and suppression of necdin expression. This signaling did not include an elevation of intracellular calcium. A constitutively active form of CREB expressed in IRS-1 knockout cells decreased necdin promoter activity, necdin mRNA, and necdin protein levels, leading to a partial restoration of differentiation. By contrast, forkhead box protein (Fox)O1, which is regulated by the phosphoinositide 3 kinase-Akt pathway, increased necdin promoter activity. Based on reporter gene assays using truncations of the necdin promoter and chromatin immunoprecipitation studies, we demonstrated that CREB and FoxO1 are recruited to the necdin promoter, likely interacting with specific consensus sequences in the proximal region. Based on these results, we propose that insulin/IGF-I act through IRS-1 phosphorylation to stimulate differentiation of brown preadipocytes via two complementary pathways: 1) the Ras-ERK1/2 pathway to activate CREB and 2) the phosphoinositide 3 kinase-Akt pathway to deactivate FoxO1. These two pathways combine to decrease necdin levels and permit the clonal expansion and coordinated gene expression necessary to complete brown adipocyte differentiation.
Indexed as
Identifiers
What OpenQuestion holds
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.