ArticleInternational journal of biological sciences2017
Downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes.
Article in International journal of biological sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.
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Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.
- Pooled it
- Emerging Role of Epitranscriptomics in Diabetes Mellitus and Its Complications.Frontiers in endocrinology · 2022Pooled it
- Lipin3 deficiency promotes hepatocyte ferroptosis and pyroptosis via activating JAK1-STAT3 pathway during acetaminophen induced acute liver injury.Molecular biomedicine · 2025Article
- Lipin-1 Drives Browning of White Adipocytes via Promotion of Brown Phenotype Markers.Biomedicines · 2025Article
- Lipin-1 restrains macrophage lipid synthesis to promote inflammation resolution.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Research progress on the role of FGF21 in insulin resistance.Frontiers in endocrinology · 2025Review
- Experimental cell models of insulin resistance: overview and appraisal.Frontiers in endocrinology · 2024Review
- Lipin-1 restrains macrophage lipid synthesis to promote inflammation resolution.bioRxiv : the preprint server for biology · 2023Article
- N6-methyladenosine RNA modification: an emerging molecule in type 2 diabetes metabolism.Frontiers in endocrinology · 2023Review
- Insulin Signal Transduction Perturbations in Insulin Resistance.International journal of molecular sciences · 2021Review
- Diverse roles of phosphatidate phosphatases in insect development and metabolism.Insect biochemistry and molecular biology · 2021Review
- Distinct infrastructure of lipid networks in visceral and subcutaneous adipose tissues in overweight humans.The American journal of clinical nutrition · 2020Article
- mGenomics, proteomics & bioinformatics · 2020Article
- Approaches for probing and evaluating mammalian sphingolipid metabolism.Analytical biochemistry · 2019Review
- Sphingolipid Metabolism: New Insight into Ceramide-Induced Lipotoxicity in Muscle Cells.International journal of molecular sciences · 2019Review
- Transcriptomic Responses of Skeletal Muscle to Acute Exercise in Diabetic Goto-Kakizaki Rats.Frontiers in physiology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of lipid metabolism in skeletal muscle is involved in the development of insulin resistance. Mutations in lipin-1, a key lipid metabolism regulator leads to significant systemic insulin resistance in fld mice. However, the function of lipin-1 on lipid metabolism and insulin sensitivity in skeletal muscle is still unclear. Herein we demonstrated that downregulation of lipin-1 in C2C12 myotubes by siRNA transfection suppressed insulin action, characterized by reduced insulin stimulated Akt phosphorylation and glucose uptake. Correspondingly, decreased lipin-1 expression was observed in palmitate-induced insulin resistance in C2C12 myotubes, suggested that lipin-1 might play a role in the etiology of insulin resistance in skeletal muscle. The insulin resistance induced by lipin-1 downregulation was related to the disturbance of lipid homeostasis. Lipin-1 silencing reduced intracellular DAG and TAG levels, but elevated ceramide accumulation in C2C12 myotubes. Moreover, the impaired insulin stimulated Akt phosphorylation and glucose uptake caused by lipin-1 silencing could be blocked by the pretreatment with SPT inhibitor myriocin, ceramide synthase inhibitor FB1, or PP2A inhibitor okadaic acid, suggested that the increased ceramide accumulation might be responsible for the development of insulin resistance induced by lipin-1 silencing in C2C12 myotubes. Meanwhile, decreased lipin-1 expression also impaired mitochondrial function in C2C12 myotubes. Therefore, our study suggests that lipin-1 plays an important role in lipid metabolism and downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes. These results offer a molecular insight into the role of lipin-1 in the development of insulin resistance in skeletal muscle.
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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.