Observational studyNature communications2021
Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue.
Observational study in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 54 citations in OpenAlex.
- Review
- Insights into taurine therapy for periodontitis: Targeting osteocyte ferroptosis to mitigate obesity-exacerbated bone damage.Redox biology · 2026Article
- The therapeutic potential of orphan adhesion G-protein-coupled receptors.Nature reviews. Drug discovery · 2026Review
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Endothelial ADGRF5(GPR116) governs vascular adaptation required for sustained thermogenic remodeling of brown adipose tissue.Molecular metabolism · 2026Article
- Alcohol use disorder-associated gene FNDC4 alters glutamatergic and GABAergic neurogenesis in neural organoids.The Journal of clinical investigation · 2026Article
- FNDC4 Drives Metastasis and Immune Evasion in Pancreatic Cancer.Cancer research · 2026Article
- Orphan GPCRs in diabetes mellitus: metabolic control, inflammation, and drug development.Frontiers in endocrinology · 2026Review
- Estimated glucose disposal rate and its dual role in hyperlipidemia risk and mortality: a secondary analysis of retrospective cohort data from U.S. and Chinese.Lipids in health and disease · 2025Article
- Exploring the role of lipid metabolism related genes and immune microenvironment in periodontitis by integrating machine learning and bioinformatics analysis.Scientific reports · 2025Article
- FNDC4 Prevents Aging-Related Cardiac Dysfunction: By Restoring AMPKα/PPARα-Dependent Mitochondrial Function.JACC. Basic to translational science · 2025Article
- Increased expression of IL-1β in adipose tissue in obesity influences the development of colon cancer by promoting inflammation.Journal of physiology and biochemistry · 2025Article
- Mechanosensitive adhesion G protein-coupled receptors: Insights from health and disease.Genes & diseases · 2025Review
- Plasma from hypertensive pregnancy patients induce endothelial dysfunction even under atheroprotective shear stress.Scientific reports · 2025Article
- Glucose sensing and homeostasis by adipocyte GPCR.Frontiers in endocrinology · 2025Review
- Cgref1 is a CREB-H-regulated hepatokine that promotes hepaticInternational journal of biological sciences · 2025Article
- FNDC4 alleviates cardiac ischemia/reperfusion injury through facilitating HIF1α-dependent cardiomyocyte survival and angiogenesis in male mice.Nature communications · 2024Article
- Prevention and treatment of peri-implant fibrosis by functionally inhibiting skeletal cells expressing the leptin receptor.Nature biomedical engineering · 2024Article
- GPR116 alleviates acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress.Cellular and molecular life sciences : CMLS · 2024Article
- The adhesion-GPCR ADGRF5 fuels breast cancer progression by suppressing the MMP8-mediated antitumorigenic effects.Cell death & disease · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
37 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.
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.