Therapeutic potential of oleic acid supplementation in myotonic dystrophy muscle cell models

Background We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the muscle catabolic processes autophagy and UPS through a reduction in miR-7 levels. Because oleic acid (OA) is a known allosteric regulator of MSI2 activity in the biogenesis of miR-7, here we sought to evaluate endogenous levels of this fatty acid and its therapeutic potential in rescuing cell differentiation phenotypes in vitro. In this work, four muscle cell lines derived from DM1 patients were treated with OA for 24 h, and autophagy and muscle differentiation parameters were analyzed. Results We demonstrate a reduction of OA levels in different cell models of the disease. OA supplementation rescued disease-related phenotypes such as fusion index, myotube diameter, and repressed autophagy. This involved inhibiting MSI2 regulation of direct molecular target miR-7 since OA isoschizomer, elaidic acid (EA) could not cause the same rescues. Reduction of OA levels seems to stem from impaired biogenesis since levels of the enzyme stearoyl-CoA desaturase 1 (SCD1), responsible for converting stearic acid to oleic acid, are decreased in DM1 and correlate with OA amounts. Conclusions For the first time in DM1, we describe a fatty acid metabolism impairment that originated, at least in part, from a decrease in SCD1. Because OA allosterically inhibits MSI2 binding to molecular targets, reduced OA levels synergize with the overexpression of MSI2 and contribute to the MSI2 > miR-7 > autophagy axis that we proposed to explain the muscle atrophy phenotype.

A Scd1-mediated metabolic alteration participates in liver responses to low-dose bavachin / 药物分析学报

Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several studies have described BV-induced liver damage and underlying toxicity mechanisms,but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level,and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase,making it much harder for early recognition of hepatotoxicity.Here,we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests,but found subtle steatosis in BV-treated hepatocytes.We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver.Among these,the hepa3 subtype suffered from a vast alteration in lipid metabolism,which was characterized by enhanced expression of apolipoproteins,carboxylesterases,and stearoyl-CoA desaturase 1(Scd1).In particular,increased Scd1 promoted monounsaturated fatty acids(MUFAs)syn-thesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids(PUFAs)generation,which participates in the initiation of ferroptosis.Additionally,we demonstrated that mul-tiple intrinsic transcription factors,including Srebf1 and Hnf4a,and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes.Collectively,our study deciphered the features of hepatocytes in response to BV insult,decoded the underlying molecular mechanisms,and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.

Catechin interferes with SCD1 expression and prevents liver fibrosis in mice / 中国药理学通报

Aim To investigate whether catechin can play against CCl

Effects of SCD-1 gene overexpression on the content of calcium ion and lipids in duck uterine epithelial cells / 生物工程学报

Stearoyl-CoAdesaturase-1 (SCD-1) is a key regulator of monounsaturated fatty acid synthesis. It plays a vital role in lipid synthesis and metabolism. Ca²⁺ is an important cation in the body and plays an important role in the organism. The aims of this study were to investigate the correlation of SCD-1 gene overexpression with lipid indexes and calcium ion level. The pcDNA3.1 (+) + SCD-1 +Flag eukaryotic expression vector and cultured duck uterine epithelial cells were co-transfected. The overexpression of SCD-1 gene was measured using the Flag Label Detection Kit. Ca ions and lipid contents were detected through Fluo-3/AM Calcium Ion Fluorescence Labeling method and Lipid Measuring Kit, respectively. SCD-1 gene overexpression was negatively correlated with triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), and positively correlated with Ca ion, total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C) and low density lipoprotein cholesterol (LDL-C) levels. Meanwhile, Ca ion was positively correlated with TG, LDL-C and HDL-C contents, and negatively correlated with TC and VLDL-C levels. Overexpression of SCD-1 gene could regulate Ca ion secretion, as well as lipid synthesis and transport in duck uterine epithelial cells.

RASAL1 induces to downregulate the SCD1, leading to suppression of cell proliferation in colon cancer via LXRα/SREBP1c pathway

BACKGROUND: Recent studies have confirmed that RASAL1 has an antitumor effect in many cancers, but its functional role and the molecular mechanism underlying in colon cancer has not been investigated. RESULTS: We collected human colon cancer tissues and adjacent non-tumor tissues, human colon cancer cell lines LoVo, CaCo2, SW1116, SW480 and HCT-116, and normal colonic mucosa cell line NCM460. RT-qPCR was used to detect the RASAL1 level in the clinical tissues and cell lines. In LoVo and HCT-116, RASAL1 was artificially overexpressed. Cell viability and proliferation were measured using CCK-8 assays, and cell cycle was detected via PI staining and flow cytometry analysis. RASAL1 significantly inhibited the cell proliferation via inducing cell cycle arrest, suppressed cell cycle associated protein expression, and decreased the lipid content and inhibited the SCD1 expression. Moreover, SCD1 overexpression induced and downregulation repressed cell proliferation by causing cell cycle arrest. Additionally, luciferase reporter assays were performed to confirm the direct binding between SREBP1c, LXRα; and SCD1 promoter, we also demonstrated that RASAL1 inhibit SCD1 3'-UTR activity. RASAL1 inhibited tumor growth in xenograft nude mice models and shows inhibitory effect of SCD1 expression in vivo. CONCLUSION: Taken together, we concluded that RASAL1 inhibited colon cancer cell proliferation via modulating SCD1 activity through LXRα/SREBP1c pathway.

Effects of Hedysarum Polybotys Saccharide on Lipid Metabolism and Expression of Stearoyl-CoA Desaturase-1 Gene in NAFLD Rats / 中国中医药信息杂志

Objective To investigate the effects of hedysarum polybotys saccharide (HPS) on lipid metabolism and the expression of stearoyl-CoA desaturase-1(SCD-1) gene in rats with non-alcoholic fatty liver disease (NAFLD). To discuss the interfering effects of HPS on NAFLD. Methods The SD rats were randomly divided into the blank control group and the experiment group. Rats in the experiment group were fed with lipid rich food for 8 weeks to establish model and were randomly divided into model group, drug positive group and HPS group. After 8 weeks of drug intervention, the level of ALT, AST, TC, TG, HDL-c and LDL-c were measured with automatic chemistry analyzer, and expression of SCD-1 gene was measured by semi-quantitative polymerase chain reaction.Results Compared with blank control group, serum ALT, AST and TC, TG, LDL-c of model group were higher (P<0.05,P<0.01), the level of HDL-c of model group and the expression of SCD-1 gene were lower (P<0.01). Compared with model group, HPS was useful to decrease serum ALT, AST, LDL-c, TC and TG (P<0.05,P<0.01), and increase the level of HDL-c (P<0.01) and the expression of SCD-1 gene (P<0.01).ConclusionHPS had a positive effect on regulating lipid metabolic disturbance of NAFLD rats and promoting the expression of regulatory gene SCD-1.

EFFECT OF PU-ERH TEA ON LIPOGENESIS AND EXPRESSION OF RELATIVE GENES IN OBESE RAT FED WITH HIGH FAT DIET / 营养学报

Objective To examine the effect of Pu-Erh tea extract(PTE) on genes expression of lipogenesis in white adipose tissue of rats fed high fat diet.Method Thirty male SD rats were randomly divided into three groups(n=10):the control group(basal diet);the high fat group(high fat diet);the PTE group(high fat diet + Pu-Erh tea extract).Body weight and adipose tissue were measured.Expression of genes regulating lipid metabolism was assessed in adipose tissue.Results PTE supplementation prevented diet-induced increases in body weight and adipose tissue.Diacylglycerol acyltransferase-1(DGAT1),stearoyl-CoA desalurase-1(SCD1) and sterol regulatory element binding protein-1c(SREBP-1c) mRNA levels were markedly decreased in adipose tissue of rats fed PTE.Conclusion This study shows for the first time that Pu-Erh tea extract prevents diet-induced obesity,and this effect is partly mediated via a direct influence on adipose tissue.