ArticleFrontiers in pharmacology2020
A Class I Histone Deacetylase Inhibitor Attenuates Insulin Resistance and Inflammation in Palmitate-Treated C2C12 Myotubes and Muscle of HF/HFr Diet Mice.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Pooled it
- Modulation and Reprogramming of Adipose Tissue Macrophages in Obesity.Biomolecules · 2026Review
- Epigenetic inhibition of class I histone deacetylases by MS-275 attenuates diabetic skeletal muscle atrophy via Akt/ARK5-FoxO and myostatin-Smad signaling.Frontiers in endocrinology · 2026Article
- The role of HDAC3 in inflammation: mechanisms and therapeutic implications.Frontiers in immunology · 2024Review
- Chitosan Derivative-Based Microspheres Loaded with Fibroblast Growth Factor for the Treatment of Diabetes.Polymers · 2023Article
- [EHHADH is a key gene in fatty acid metabolism pathways in hepatocellular carcinoma: a transcriptomic analysis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Histone deacetylase functions and therapeutic implications for adult skeletal muscle metabolism.Frontiers in molecular biosciences · 2023Review
- Sodium Propionate or Sodium Butyrate Promotes Fatty Acid Oxidation in HepG2 Cells Under Oxidative Stress.Journal of medicinal food · 2023Article
- The epigenetic regulatory effect of histone acetylation and deacetylation on skeletal muscle metabolism-a review.Frontiers in physiology · 2023Review
- Pharmacoepigenetics in type 2 diabetes: is it clinically relevant?Diabetologia · 2022Article
- In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse Liver.International journal of molecular sciences · 2022Article
- H19 inhibition increases HDAC6 and regulates IRS1 levels and insulin signaling in the skeletal muscle during diabetes.Molecular medicine (Cambridge, Mass.) · 2022Article
- Glucose starvation induces a switch in the histone acetylome for activation of gluconeogenic and fat metabolism genes.Molecular cell · 2022Article
- Synthesis, Molecular Docking and Biological Characterization of Pyrazine Linked 2-Aminobenzamides as New Class I Selective Histone Deacetylase (HDAC) Inhibitors with Anti-Leukemic Activity.International journal of molecular sciences · 2021Article
- The critical roles of histone deacetylase 3 in the pathogenesis of solid organ injury.Cell death & disease · 2021Review
- Sugar Fructose Triggers Gut Dysbiosis and Metabolic Inflammation with Cardiac Arrhythmogenesis.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase (HDAC) inhibitors, which regulate gene expression by inhibiting the deacetylation of histones and nonhistone proteins, have been shown to exert a wide array of biological effects; these include anti-cancer, anti-obesity, and anti-diabetes effects, as well as cardiovascular-protective activity. However, the effects of class I HDAC inhibition on lipotoxicity in C2C12 myotubes and skeletal muscle tissue remain poorly understood. In this study, we investigated the molecular mechanism underlying the protective effect of class I HDAC inhibition under lipotoxic conditions, i.e., in palmitate (PA)-treated C2C12 myotubes and skeletal muscle tissue in high fat (HF)/high fructose (HFr) diet mice. PA treatment of C2C12 myotubes increased HDAC3 protein expression and impaired mitochondrial oxidation, resulting in increased mitochondrial ROS generation and an accumulation of intracellular triglycerides (TG). Prolonged exposure led to increased inflammatory cytokine expression and insulin resistance. In contrast, MS-275, a class I HDAC inhibitor, dramatically attenuated lipotoxicity, preventing PA-induced insulin resistance and inflammatory cytokine expression. Similar beneficial effects were also seen following HDAC3 knockdown. In addition, MS-275 increased the mRNA expression of peroxisome proliferator activator receptor γ-coactivator 1α (PGC1α) and mitochondrial transcription factor A (TFAM), which serve as transcriptional coactivators in the context of mitochondrial metabolism and biogenesis, and restored expression of peroxisome proliferator-activated receptor alpha (PPARα), medium-chain acyl-coenzyme A dehydrogenase (MCAD), enoyl-CoA hydratase, and 3-hydroxyacyl CoA dehydrogenase (EHHADH).
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