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Diabetic retinopathy (DR) is one of the most common complications of diabetes and induces severe visual impairment worldwide. Endothelial cell dysfunction plays an important role in the pathogenesis of DR. Here, we keep a watchful eye on α/β‐hydrolase domain–containing 1 (ABHD1), a potential regulator in lipid metabolism and neovascularization. Results revealed that ABHD1 expression increased both in retina tissues of DR patients and in high‐glucose–treated human retina endothelial cells. Inhibition of ABHD1 remitted endothelial cell proliferation and migration. And GSEA uncovered that ABHD1 knockdown remits endothelial cell chemotaxis and intermediate filament (IF) might be mediated in the progress by regulating keratin 1 (KRT1) and keratin 2 (KRT2). Therefore, we assume that ABHD1 is concerned with endothelial cell proliferation and migration in DR, consequently leading to pathological neovascularization. The findings may provide a potential therapeutic target for DR. [ABSTRACT FROM AUTHOR]

The Mondo family transcription factor MondoA plays a pivotal role in sensing metabolites, such as glucose, glutamine, and lactic acid, to regulate glucose metabolism and cell proliferation. Ketone bodies are important signals for reducing glucose uptake. However, it is unclear whether MondoA functions in ketone body‐regulated glucose transport. Here we reported that ketone bodies promoted MondoA nuclear translocation and binding to the promoter of its target gene TXNIP. Ketone bodies reduced glucose uptake, increased apoptosis and decreased proliferation of colorectal cancer cells, which was impeded by MondoA knockdown. Moreover, we identified MEK1 as a novel component of the MondoA protein complex using a proteomic approach. Mechanistically, MEK1 interacted with MondoA and enhanced tyrosine 222, but not serine or threonine, phosphorylation of MondoA, inhibiting MondoA nuclear translocation and transcriptional activity. Ketone bodies decreased MEK1‐dependent MondoA phosphorylation by blocking MondoA and MEK1 interaction, leading to MondoA nuclear translocation, TXNIP transcription, and inhibition of glucose uptake. Therefore, our study not only demonstrated that ketone bodies reduce glucose uptake, promote apoptosis, and inhibit cell proliferation in colorectal cancer cells by regulating MondoA phosphorylation but also identified MEK1‐dependent phosphorylation as a new mechanism to manipulate MondoA activity. [ABSTRACT FROM AUTHOR]