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Stearoyl-CoA-desaturase 1 (SCD1) deficiency mediates apoptosis in colorectal cancer cells by promoting ceramide de novo synthesis. The mechanisms underlying the cross-talk between SCD1 and ceramide synthesis have not been explored. We treated colorectal cancer cells with an SCD1 inhibitor and examined the effects on gene expression, cell growth, and cellular lipid contents. The main effect of SCD1 inhibition on the fatty acid contents of colorectal cancer cells was a decrease in monounsaturated fatty acids (MUFAs). RNA sequencing (RNA-seq) showed that the most intense alteration of gene expression after SCD1 inhibition occurred in the NF-κB signaling pathway. Further experiments revealed that SCD1 inhibition resulted in increased levels of phosphorylated NF-κB p65 and increased nuclear translocation of NF-κB p65. Treatment with an NF-κB inhibitor eliminated several effects of SCD1 inhibition, mainly including overexpression of serine palmitoyltransferase1 (SPT1), elevation of dihydroceramide contents, and suppression of cell growth. Furthermore, treatment with supplemental oleate counteracted the SCD1-induced NF-κB activation and downstream effects. In summary, our data demonstrate that the NF-κB pathway plays a role in SCD1 deficiency-induced ceramide de novo synthesis in colorectal cancer cells, and that reduced MUFA levels contribute to the course.

Acute lung injury (ALI) is a significant cause of morbidity and mortality worldwide. To search for a new treatment for acute lung injury, we investigated the effect of escitalopram on lipopolysaccharide (LPS)-induced ALI. Our results showed that escitalopram inhibited salt-inducible kinase 2 (SIK2) activity (IC

High expression of stearoyl-CoA desaturase-1 (SCD1) in meibomian glands produces monounsaturated fatty acids that allow the biosynthesis of glycerolipids and other wax-esters but only the low production of sphingolipids. Here, we found that SCD1 deficiency in mice induces the spill of free fatty acids into a parallel pathway for ceramide biosynthesis, resulting in severe meibomian gland dysfunction associated with meibum accumulation in duct lumen and orifices and subsequent atrophy and loss of acinar cells. Genetic and pharmacological inhibition of SCD1 in mice resulted in meibomian gland pathological phenotypes, including local lipid microenvironment alterations, reduced normal cellular differentiation, increased keratinization, inflammatory cell infiltration, cell apoptosis, and mitochondrial dysfunction. However, inhibition of serine palmitoyltransferase, the initial enzyme in ceramide biosynthesis, improved meibomian gland metabolism and morphology in SCD1-deficient mice, resulting in normal cell differentiation and reduced inflammation infiltration, cell apoptosis, and keratinization. These results indicate that elevated levels of endogenous ceramides are a sign of MGD and suggest that inhibition of ceramide de novo biosynthesis could be a new clinical approach to treating MGD.

The endogenous lipid metabolism network is associated with the occurrence and progression of malignancies. Endocannabinoids and ceramides have demonstrated their anti-proliferative and pro-apoptotic properties in a series of cancer studies. The aim of the present study was to evaluate the expression patterns of endocannabinoids and endogenous ceramides in 67 pairs of human hepatocellular carcinoma (HCC) tissues and non-cancerous counterpart controls. Anandamide (AEA), the major endocannabinoid, was reduced in tumor tissues, probably due to the high expression and activity of fatty acid amide hydrolase. Another important endocannabinoid, 2-arachidonylglycerol (2-AG), was elevated in tumor tissues compared with non-tumor controls, indicating that the biosynthesis of 2-AG is faster than the degradation of 2-AG in tumor cells. Furthermore, western blot analysis demonstrated that cannabinoid receptor 1 was downregulated, while cannabinoid receptor 2 was elevated in HCC tissues, in accordance with the alterations in the levels of AEA and 2-AG, respectively. For HCC tissues, the expression levels of C18:0, 20:0 and 24:0-ceramides decreased significantly, whereas C12:0, 16:0, 18:1 and 24:1-ceramides were upregulated, which may be associated with cannabinoid receptor activation and stearoyl-CoA desaturase protein downregulation. The exact role of endocannabinoids and ceramides in regulating the fate of HCC cells requires further investigation.