ArticleThe Journal of clinical investigation2016
MondoA coordinately regulates skeletal myocyte lipid homeostasis and insulin signaling.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 70 citations in OpenAlex.
- ChREBP Is Dispensable for Myofiber Type Switch but Promotes Skeletal Muscle Regeneration.Nutrients · 2026Article
- Mutations in the Txnip PPXY motifs protect against myocardial infarction despite enhanced protein stability.American journal of physiology. Heart and circulatory physiology · 2026Article
- MondoA mediates transcriptional coordination between the MYC network and the integrated stress response in pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Role of TXNIP in Skeletal Muscle Physiology and Related Diseases: Current Perspectives.Journal of inflammation research · 2026Review
- Insulin Deficiency Exacerbates Muscle Atrophy and Osteopenia inInternational journal of molecular sciences · 2025Article
- Whole body MondoA deletion protects against diet-induced obesity through uncontrolled multi-organ substrate utilization and futile cycling.bioRxiv : the preprint server for biology · 2025Article
- MondoA mediates transcriptional coordination between the MYC network and the integrated stress response in pancreatic ductal adenocarcinoma.bioRxiv : the preprint server for biology · 2025Article
- Targeting MondoA-TXNIP restores antitumour immunity in lactic-acid-induced immunosuppressive microenvironment.Nature metabolism · 2025Article
- Dual gains from targeting MondoA in T cells.Nature metabolism · 2025Article
- Role of Nutritional Elements in Skin Homeostasis: A Review.Biomolecules · 2025Review
- MAX inactivation deregulates the MYC network and induces neuroendocrine neoplasia in multiple tissues.Science advances · 2025Article
- Glucose-Sensing Carbohydrate Response Element-Binding Protein in the Pathogenesis of Diabetic Retinopathy.Cells · 2025Article
- Mondo family proteins in diabetes.Frontiers in endocrinology · 2025Review
- Glucose-Sensing ChREBP Protein in the Pathogenesis of Dia-betic Retinopathy.bioRxiv : the preprint server for biology · 2024Article
- Systemic Deletion of ARRDC4 Improves Cardiac Reserve and Exercise Capacity in Diabetes.Circulation research · 2024Article
- Rutin attenuates ensartinib-induced hepatotoxicity by non-transcriptional regulation of TXNIP.Cell biology and toxicology · 2024Article
- The transcription factor ChREBP Orchestrates liver carcinogenesis by coordinating the PI3K/AKT signaling and cancer metabolism.Nature communications · 2024Article
- Glucose-induced and ChREBP: MLX-mediated lipogenic program promotes hepatocellular carcinoma development.Oncogene · 2023Article
- Identification of candidate genes and chemicals associated with osteoarthritis by transcriptome-wide association study and chemical-gene interaction analysis.Arthritis research & therapy · 2023Article
- The role of ChREBP in carbohydrate sensing and NAFLD development.Nature reviews. Endocrinology · 2023Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Intramuscular lipid accumulation is a common manifestation of chronic caloric excess and obesity that is strongly associated with insulin resistance. The mechanistic links between lipid accumulation in myocytes and insulin resistance are not completely understood. In this work, we used a high-throughput chemical biology screen to identify a small-molecule probe, SBI-477, that coordinately inhibited triacylglyceride (TAG) synthesis and enhanced basal glucose uptake in human skeletal myocytes. We then determined that SBI-477 stimulated insulin signaling by deactivating the transcription factor MondoA, leading to reduced expression of the insulin pathway suppressors thioredoxin-interacting protein (TXNIP) and arrestin domain-containing 4 (ARRDC4). Depleting MondoA in myocytes reproduced the effects of SBI-477 on glucose uptake and myocyte lipid accumulation. Furthermore, an analog of SBI-477 suppressed TXNIP expression, reduced muscle and liver TAG levels, enhanced insulin signaling, and improved glucose tolerance in mice fed a high-fat diet. These results identify a key role for MondoA-directed programs in the coordinated control of myocyte lipid balance and insulin signaling and suggest that this pathway may have potential as a therapeutic target for insulin resistance and lipotoxicity.
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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.