Trial reportNature communications2015
A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis.
Trial report in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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
54 citing papers in PubMed, 86 citations in OpenAlex.
- Inhibition of IKKɛ and TBK1 Improves Glucose Control in a Subset of Patients with Type 2 Diabetes.Cell metabolism · 2017Trial
- Hepatic gluconeogenesis and PDK3 upregulation drive cancer cachexia in flies and mice.Nature metabolism · 2025Article
- Amlexanox targeted inhibition of TBK1 regulates immune cell function to exacerbate DSS-induced inflammatory bowel disease.Clinical and experimental immunology · 2025Article
- TBK1 inhibitor amlexanox exerts anti-cancer effects against endometrial cancer by regulating AKT/NF-κB signaling.International journal of biological sciences · 2025Article
- Unlocking therapeutic potential of amlexanox in MASH with insights into bile acid metabolism and microbiome.Npj gut and liver · 2025Article
- Amlexanox Enforces Osteogenic Differentiation and Bone Homeostasis Through Inhibiting Ubiquitin-Dependent Degradation of β-Catenin.International journal of biological sciences · 2024Article
- Article
- Silencing IKBKE inhibits the migration and invasion of glioblastoma by promoting Snail1 degradation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- Nonalcoholic Fatty Liver Disease.Handbook of experimental pharmacology · 2022Review
- Role of IKKε in the Metabolic Diseases: Physiology, Pathophysiology, and Pharmacology.Frontiers in pharmacology · 2022Review
- A potential probiotic bacterium for antipsychotic-induced metabolic syndrome: mechanisms underpinning how Akkermansia muciniphila subtype improves olanzapine-induced glucose homeostasis in mice.Psychopharmacology · 2021Article
- Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential.International journal of molecular sciences · 2021Review
- FGF21 is required for the metabolic benefits of IKKε/TBK1 inhibition.The Journal of clinical investigation · 2021Article
- Mice with Fabp4-Cre ablation of Arid5b are resistant to diet-induced obesity and hepatic steatosis.Molecular and cellular endocrinology · 2021Article
- Obesity of mice lacking VAP-1/SSAO by Aoc3 gene deletion is reproduced in mice expressing a mutated vascular adhesion protein-1 (VAP-1) devoid of amine oxidase activity.Journal of physiology and biochemistry · 2021Article
- Comparing the effects of two different strains of mycobacteria, Mycobacterium vaccae NCTC 11659 and M. vaccae ATCC 15483, on stress-resilient behaviors and lipid-immune signaling in rats.Brain, behavior, and immunity · 2021Article
- Amlexanox: A Novel Therapeutic for Atopic, Metabolic, and Inflammatory Disease.The Yale journal of biology and medicine · 2020Review
- TANK-Binding Kinase 1 Regulates the Localization of Acyl-CoA Synthetase ACSL1 to Control Hepatic Fatty Acid Oxidation.Cell metabolism · 2020Article
- PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans.Science translational medicine · 2020Article
- SQSTM1/p62 Controls mtDNA Expression and Participates in Mitochondrial Energetic Adaption via MRPL12.iScience · 2020Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
The search for effective treatments for obesity and its comorbidities is of prime importance. We previously identified IKK-ε and TBK1 as promising therapeutic targets for the treatment of obesity and associated insulin resistance. Here we show that acute inhibition of IKK-ε and TBK1 with amlexanox treatment increases cAMP levels in subcutaneous adipose depots of obese mice, promoting the synthesis and secretion of the cytokine IL-6 from adipocytes and preadipocytes, but not from macrophages. IL-6, in turn, stimulates the phosphorylation of hepatic Stat3 to suppress expression of genes involved in gluconeogenesis, in the process improving glucose handling in obese mice. Preliminary data in a small cohort of obese patients show a similar association. These data support an important role for a subcutaneous adipose tissue-liver axis in mediating the acute metabolic benefits of amlexanox on glucose metabolism, and point to a new therapeutic pathway for 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.