DPP3 promotes breast cancer tumorigenesis by stabilizing FASN and promoting lipid synthesis.

DPP3, a dipeptidyl peptidase, participates in a variety of pathophysiological processes. DPP3 is upregulated in cancer and might serve as a key factor in the tumorigenesis and progression of various malignancies. However, its specific role and molecular mechanism are still unknown. In this study, the expression of DPP3 in breast cancer tissues is analyzed using TCGA database. Kaplan-Meier survival analysis is performed to estimate the effect of DPP3 on the survival outcomes. To explore the biological function and mechanisms of DPP3 in breast cancer, biochemical and cell biology assays are conducted in vitro. DPP3 expresses at a higher level in breast cancer tissues than that in adjacent tissues in both TCGA database and clinical samples. Patients with high expression of DPP3 have poor survival outcomes. The proliferation and migration abilities of tumor cells with stable DPP3 knockout in breast cancer cell lines are significantly inhibited, and apoptosis is increased in vitro. GSEA analysis shows that DPP3 can affect lipid metabolism and fatty acid synthesis in tumors. Subsequent experiments show that DPP3 could stabilize FASN expression and thus promote fatty acid synthesis in tumor cells. The results of the metabolomic analysis also confirm that DPP3 can affect the content of free fatty acids. This study demonstrates that DPP3 plays a role in the reprogramming of fatty acid metabolism in tumors and is associated with poor prognosis in breast cancer patients. These findings will provide a new therapeutic target for the treatment of breast cancer.

Taurine supplementation alters gene expression profiles in white adipose tissue of obese C57BL/6J mice: Inflammation and lipid synthesis perspectives.

This work aimed to identify the mechanisms by which taurine exerts its anti-obesity effects in the C57BL/6J ob/ob mice model and determine if taurine supplementation increases the amelioration of inflammation and lipogenesis linked genes in the adipose and liver tissues. Three groups of C57BL/6J mice were fed a standard chow diet for a period of 10 weeks the C57BL/6J normal group, the C57BL/6J ob/ob negative control group with no taurine intake and C57BL/6J ob/ob taurine group with taurine intake. Real time PCR was used to examine the gene expression profile in the experimental groups intrascapular brown adipose tissue (BAT), inguinal white adipose tissue (WAT) and liver. TNF-alpha, Ccl2, Adgre and illb genes that are associated with inflammation were found to have varying level of expression in the three tissues. In comparison to BAT and liver these genes were expressed at a much lower level in WAT, with enhanced serum adiponectin levels.

Effect of Dietary Manganese on the Growth Performance, Lipid Metabolism, and Antioxidant Capacity in the Post-Larval Coho Salmon (Oncorhynchus kisutch).

In this study, post-larval coho salmon Oncorhynchus kisutch (initial weight 0.37 ± 0.03 g) were fed with 6 experimental diets with increasing manganese (Mn) content (2.4, 8.5, 14.8, 19.8, 24.6, and 33.7 mg kg-1) for 12 weeks. Our results indicated that the feed conversion rate (FCR), specific growth rate (SGR), condition factor (CF), crude protein, moisture, crude lipid, ash, whole-body Mn, and vertebral Mn were affected by the elevation of Mn content in the diet. The activities of hepatic GSH-PX, Mn-SOD, and CAT were enhanced with increasing Mn content in the diet and reached the highest value at 19.8 mg kg-1 Mn. However, the level of hydrogen peroxide (H2O2), superoxide anion (O2·-), and malondialdehyde (MDA) was reduced with increasing Mn content in the diet. In addition, the activity of hepatic lipase (HL) and lipoprotein lipase (LPL) was increased with the elevation of dietary Mn content and reached a peak value at 14.8 mg kg-1 Mn. The activity of fatty acid synthetase (FAS) and the content of nonesterified fatty acid (NEFA) were increased following the elevation of Mn content from 2.4 to 19.8 mg kg-1 in the diet. The results indicated that the appropriate dietary Mn supplementation improved the feeding efficiency, lipid metabolism, and antioxidant capacity of coho salmon. The dietary Mn requirement for post-larval coho salmon was 17.35 mg kg-1 and 19.75 mg kg-1 based on the SGR and FCR, respectively. An optimal dietary level of Mn enhances hepatic lipid metabolism, and the signaling pathway of PI3K/AKT/mTOR may be involved in regulating the activity of enzymes related to lipid metabolism.

Dietary iron affects lipid deposition, nutritional element, and muscle quality in coho salmon (Oncorhynchus kisutch).

We investigated effect of dietary iron (Fe) on the lipid deposition, nutritional element, and muscle quality in coho salmon. Four level Fe diets at 23.7, 46.4, 77.3, and 127.7 mg/kg were fed to the post-larval coho salmon for 12 weeks. Our results showed that dietary Fe decreased the content of triglyceride and the activity of fatty acid synthetase, ATP-citrate lyase, and acetyl-CoA carboxylase. The content of Fe in muscle was increased with increasing dietary Fe levels, and dietary Fe affected the content of nutritional elements. In addition, dietary Fe levels affected the composition of fatty acids and the content of free amino acids, and increased muscle fiber size. The lower dietary Fe levels also affected the hardness, chewiness, resilience, springiness, cohesiveness, and gumminess of salmon muscle. In all, dietary Fe inhibited the lipid deposition and affected the content of nutritional element and muscle quality in coho salmon.

TGF-β1 promotes migration and invasion of gastric cancer cells by regulating fatty acid synthase / 中国肿瘤临床

Objective: To investigate the effect of TGF-β1 on the migration and invasion of gastric cancer cells, by regulating fatty acid synthetase. Methods: From January 2016 to December 2018, 54 paraffin samples were collected from Shunde Hospital of Southern Medical University. Immunohistochemistry was used to detect the expression of transforming growth factor β1 (TGF-β1) and fatty acid synthetase (FASN) in human gastric cancer tissues, and the correlation between them was analyzed. Transient transfection of TGF-β1 and TGF-β1 siRNA was used to construct gastric cancer cell lines. Real-time PCR was used to detect FASN mRNA level, and Western blot was performed to examine FASN protein level. Transient transfection of FASN siRNA was used to construct gastric cancer cell lines. Wound healing assays and Transwell assays were performed to observe the effect of migration and invasion ability of gastric cancer cells. Results: Immunohistochemical results indicated that the expression of TGF-β1 and FASN in gastric cancer tissue was significantly positively correlated. TGF-β1 overexpression plasmid transfection significantly up-regulated the expression level of FASN mRNA and protein, whereas TGF-β1 siRNA significantly inhibited the expression of FASN. After co-transfection with FASN siRNA, TGF-β 1-induced N-cadherin protein expression was reduced and E-cadherin protein expression was enhenced. Scratch and Transwell experiments showed that the increased cell migration and invasion by TGF-β1 were significantly decreased. Conclusions: FASN plays an important role in the migration and invasion of gastric cancer cells regulated by TGF-β1.

Protective effect of Xiaochaihu Decoction on non-alcoholic steatohepatitis model mice / 中草药

Objective: The protective effect of Xiaochaihu Decoction on non-alcoholic steatohepatitis (NASH) model mice was studied by constructing a methionine-choline deficiency (MCD) diet-induced NASH model in mice. Methods: C57BL/6 mice, as the research objects, were randomly divided into normal control group, model group, Xiaochaihu Decoction (high, medium and low doses) group, Yishanfu group and Qianggan Capsule group. The NASH model was established by feeding MCD feeds, and model intervention was carried out at the same time by giving different drugs in groups; Changes in body weight, daily food intake, and daily water volume of the mice were recorded during the experiment. HE staining of liver tissue was performed at the end of the experiment to observe pathological changes. and the levels of biochemical indicator of alanine aminotransferase (ALT), Aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum, and the changes of TC and TG levels in liver tissue were detected, RT-PCR was used to detect the expression levels of fatty acid synthase (FAS) and sterol regulatory element binding protein 1c (SREBP-1c) in liver tissues. Results: Data such as mouse weight, daily food intake, daily water intake, and organ coefficients indicated that MCD diet-induced model mice showed weight loss, decreased intake, and decreased liver wet weight. The weight, intake and liver coefficient of mice in Xiaochaihu Decoction group were significantly higher than those in the model group; The results of HE staining showed that Xiaochaihu Decoction could significantly reduce the degree of steatosis and inflammation of liver tissue, and improve the morphology and structure of liver cells; The results of serum biochemical indicators showed that Xiaochaihu Decoction significantly reduced the levels of TG, TC, AST, ALT, IL-6, TNF-α and increased the level of HDL-C in NASH model mice; RT-PCR results showed that the gene expression levels of FAS and SREBP-1c in the liver tissue of the model group mice were significantly increased, and the administration of Xiaochaihu Decoction could significantly reduce the gene expression levels of FAS and SREBP-1c. Conclusion: Xiaochaihu Decoction has obvious protective effect on NASH mouse model induced by MCD diet. It may play a lipid-lowering role by regulating the expression of inhibitors of fatty acid synthetase genes (FAS, SREBP-1c), reducing fat accumulation, and inhibiting the expression of inflammatory factors to improve liver tissue damage.

Inhibitory effect of resveratrol on fat synthesis in liver cancer HepG2 cells and its mechanism / 吉林大学学报(医学版)

Objective: To investigate the effect of resveratrol (Res) on the fat synthesis in the liver cancer HepG cells, and to elucidate its possible mechanism. Methods: The HepG cells were cultured in vitro and divided into Res group (treated with 40 umol • L-1 DMSO- diluted Res for 24 h) and control group (treated with the same concentration of DMSO for 24 h). The cell supernatant was collected, and the levels of triglyceride (TG) and total cholesterol (TO in the cells in various groups were measured by ELISA. The mRNA and protein expression levels of lipase synthase acetyl-CoA carboxylase (ACCl), fatty acid synthetase (FASN) and stearoyl-CoA desaturase (SCD1) in the cells in various groups were detected by qRT-PCR and Western blotting method. The levels of O-linked N-acetylglucosamine (O-GIcNAc) glycosylation in the cells in various groups were detected by Western blotting method. Results: Compared with control group, the levels of TG and TC in the cells in Res group were decreased, but the difference was not statistically significant (t1=1.886, P>0.05; t2=2.457,P>0.05). Compared with control group, the levels of expressions of ACCl, FASN and SCD1 mRNA and proteins in the cells in Res group were significantly decreased ( P<0.05 or P<0. 01); the O-GlcNAc glycosylation level in the cells in Res group was significantly decreased (t=2. 87, P<0.05). Conclusion: Res lias the effect of inhibiting the fat synthesis in the liver cancer HepG cells. Its mechanism may be related to the reduction of cellular O-GlcNAc glycosylation level and the reduction of the expression of FASN.

Inhibitory effect of resveratrol on fat synthesis in liver cancer HepG2 cells and its mechanism / 吉林大学学报(医学版)

Objective:To investigate the effect of resveratrol (Res) on the fat synthesis in the liver cancer HepG2cells, and to elucidate its possible mechanism.Methods:The HepG2cells were cultured in vitro and divided into Res group (treated with 40μmol·L-1 DMSO-diluted Res for 24h) and control group (treated with the same concentration of DMSO for 24h) .The cell supernatant was collected, and the levels of triglyceride (TG) and total cholesterol (TC) in the cells in various groups were measured by ELISA.The mRNA and protein expression levels of lipase synthase acetyl-CoA carboxylase (ACC1) , fatty acid synthetase (FASN) and stearoyl-CoA desaturase (SCD1) in the cells in various groups were detected by qRT-PCR and Western blotting method.The levels of O-linked N-acetylglucosamine (O-GlcNAc) glycosylation in the cells in various groups were detected by Western blotting method.Results:Compared with control group, the levels of TG and TC in the cells in Res group were decreased, but the difference was not statistically significant (t1=1.886, P＞0.05;t2=2.457, P＞0.05) .Compared with control group, the levels of expressions of ACC1, FASN and SCD1mRNA and proteins in the cells in Res group were significantly decreased (P＜0.05or P＜0.01) ;the O-GlcNAc glycosylation level in the cells in Res group was significantly decreased (t=2.87, P＜0.05) .Conclusion:Res has the effect of inhibiting the fat synthesis in the liver cancer HepG2 cells.Its mechanism may be related to the reduction of cellular O-GlcNAc glycosylation level and the reduction of the expression of FASN.

Effects of fasting on the activities and mRNA expression levels of lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and fatty acid synthetase (FAS) in spotted seabass Lateolabrax maculatus.

To investigate the effects of fasting on lipid metabolism in spotted seabass muscle and liver tissues, we analyzed mRNA levels and enzyme activities of lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and fatty acid synthetase (FAS), and the relationship among fat content, mRNA level, and enzyme activity during fasting of 35 days. The results showed that expressions of all the three genes were ubiquitous. During the fasting experiment, the hepatosomatic index (HSI) and fat content of muscle and liver tissues significantly decreased before 5 days of fasting (P < 0.05). mRNA levels of LPL increased significantly after 5 days of fasting in liver and 7 days in muscle. Abundance of HSL transcripts increased significantly after 14 days of fasting in both muscle and liver. The activities of LPL and HSL presented a trend that increased firstly, decreased subsequently, and then raised again with the prolonged fasting experiment (P < 0.05). However, activities and mRNA levels of FAS decreased significantly after 1 day of fasting in both muscle and liver. Moreover, activities and mRNA levels of FAS showed a moderate correlation in muscle. These results suggested that FAS had a sooner response to fasting than LPL and HSL in both muscle and liver tissues. LPL and HSL played important roles in lipolysis mainly by increasing enzyme activities in the early stage of fasting and mRNA levels in the later stage of fasting in both muscle and liver. Our results also provided useful information on regulating muscle fat content by fasting.

Identification of Novel Alleles Conferring Superior Production of Rose Flavor Phenylethyl Acetate Using Polygenic Analysis in Yeast.

Flavor compound metabolism is one of the last areas in metabolism where multiple genes encoding biosynthetic enzymes are still unknown. A major challenge is the involvement of side activities of enzymes having their main function in other areas of metabolism. We have applied pooled-segregant whole-genome sequence analysis to identify novel Saccharomyces cerevisiae genes affecting production of phenylethyl acetate (2-PEAc). This is a desirable flavor compound of major importance in alcoholic beverages imparting rose- and honey-like aromas, with production of high 2-PEAc levels considered a superior trait. Four quantitative trait loci (QTLs) responsible for high 2-PEAc production were identified, with two loci each showing linkage to the genomes of the BTC.1D and ER18 parents. The first two loci were investigated further. The causative genes were identified by reciprocal allele swapping into both parents using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9. The superior allele of the first major causative gene, FAS2, was dominant and contained two unique single nucleotide polymorphisms (SNPs) responsible for high 2-PEAc production that were not present in other sequenced yeast strains. FAS2 encodes the alpha subunit of the fatty acid synthetase complex. Surprisingly, the second causative gene was a mutant allele of TOR1, a gene involved in nitrogen regulation. Exchange of both superior alleles in the ER18 parent strain increased 2-PEAc production 70%, nearly to the same level as in the best superior segregant. Our results show that polygenic analysis combined with CRISPR/Cas9-mediated allele exchange is a powerful tool for identification of genes encoding missing metabolic enzymes and for development of industrial yeast strains generating novel flavor profiles in alcoholic beverages.IMPORTANCE Multiple reactions in flavor metabolism appear to be catalyzed by side activities of other enzymes that have been difficult to identify. We have applied genetic mapping of quantitative trait loci in the yeast Saccharomyces cerevisiae to identify mutant alleles of genes determining the production of phenylethyl acetate, an important flavor compound imparting rose- and honey-like aromas to alcoholic beverages. We identified a unique, dominant allele of FAS2 that supports high production of phenylethyl acetate. FAS2 encodes a subunit of the fatty acid synthetase complex and apparently exerts an important side activity on one or more alternative substrates in flavor compound synthesis. The second mutant allele contained a nonsense mutation in TOR1, a gene involved in nitrogen regulation of growth. Together the two alleles strongly increased the level of phenylethyl acetate. Our work highlights the potential of genetic mapping of quantitative phenotypic traits to identify novel enzymes and regulatory components in yeast metabolism, including regular metabolic enzymes with unknown side activities responsible for biosynthesis of specific flavor compounds. The superior alleles identified can be used to develop industrial yeast strains generating novel flavor profiles in alcoholic beverages.

Inhibition of Coicis Semen oil on human prostate cancer PC-3 cells / 中草药

Objective To investigate the inhibitory effect of Coicis Semen oil on human prostate cancer PC-3 cell. Methods A Nude mice xenograft model was established with human prostate cancer PC-3 cells. Meanwhile, intragastric administration with Coicis Semen oil 2 mL/kg and 6 mL/kg was run for once daily and growth-curve was drawn through measuring the tumor volume until 26 d. At the end of the experiment, tumor weights were measured and the tumor inhibition rate of each group was calculated. The activity of fatty acid synthase (FAS) was determined through UV-VIS spectrophotometry. PC-3 cells were cultured in vitro. SYBR Green I real-time quantitative RT-PCR was used to determine the relative expression of FAS mRNA. Results The tumor inhibition rate of Coicis Semen oil 6 mL/kg group was 43.9%. Compared with model group, FAS activity in this tumor tissue decreased by 44.7% (P < 0.05). The expression of FAS mRNA was significantly decreased at 20 μL/mL of Coicis Semen oil group (P < 0.05). Conclusion Coicis Semen oil on human prostate cancer PC-3 cells has a significant inhibitory effect. FAS activity and mRNA expression decline may be related to its main anti-cancer mechanism.

Changes of serum fatty acid synthase, carcinoembryonic antigen and carbohydrate antigen 72-4 in patients with gastric cancer and its clinical diagnostic value / 中国医师杂志

Objective To analyze the changes of serum fatty acid synthase (FAS),carcinoembryonic antigen (CEA) and carbohydrate antigen 72-4 (CA72-4) in patients with gastric cancer and its clinical diagnostic value.Methods Forty five patients with gastric cancer and 45 patients with benign gastric cancer treated in our hospital from January 2016 to December 2016 were enrolled in this study.Forty five healthy subjects were enrolled in this study.The levels of FAS,CEA,and CA72-4 in three groups were analyzed.Results The levels of FAS,CEA,and CA72-4 in patients with gasttric cancer [(12.73 ± 5.48) mg/L,(31.36 ± 14.51) ng/ml,and (39.32 ± 18.76) U/ml] were significantly higher than those in benign gastric cancer group [(2.26 ± 1.15) ng/L,(3.24 ± 1.47) ng/ml,and (3.75 ± 1.69) U/ml],and normal control group [(1.83 ± 0.92) mg/L,(2.71 ± 1.54) ng/ml,and (3.13 ± 1.82) U/ml] (P ＜ 0.05).FAS,CEA,and CA72-4 levels in patients with lymph node metastasis of gastric cancer [(13.58 ± 6.09) mg/L,(6.25 ± 11.54) ng/ml,and (41.31 ± 13.67) U/ml] were significantly higher than those without lymph node metastasis [(9.21 ± 5.42) mg/L,(28.38 ± 9.72) ng/ml,and (26.75 ± 11.86) U/ml] (P ＜ 0.05).The sensitivity of FAS,CEA,and CA72-4 in patients with gastric cancer was significantly lower than that in combined detection,the specificity of FAS,CEA,and CA72-4 in patients with gastric cancer was significantly higher than that in combination test (P ＜ 0.05).The sensitivity of FAS,CEA,and CA72-4 in patients with lymph node metastasis was significantly lower than that in combination test,and the specificity of FAS,CEA and CA72-4 was significantly higher than that of combined detection (P ＜ 0.05).Conclusions FAS,CEA,and CA72-4 can be used as indicators of gastric cancer and diagnosis of lymph node metastasis.Combined detection of three indexes can improve the diagnostic sensitivity and have good clinical significance.

Changes of serum fatty acid synthase, carcinoembryonic antigen and carbohydrate antigen 72-4 in patients with gastric cancer and its clinical diagnostic value / 中国医师杂志

Objective To analyze the changes of serum fatty acid synthase (FAS),carcinoembryonic antigen (CEA) and carbohydrate antigen 72-4 (CA72-4) in patients with gastric cancer and its clinical diagnostic value.Methods Forty five patients with gastric cancer and 45 patients with benign gastric cancer treated in our hospital from January 2016 to December 2016 were enrolled in this study.Forty five healthy subjects were enrolled in this study.The levels of FAS,CEA,and CA72-4 in three groups were analyzed.Results The levels of FAS,CEA,and CA72-4 in patients with gasttric cancer [(12.73 ± 5.48) mg/L,(31.36 ± 14.51) ng/ml,and (39.32 ± 18.76) U/ml] were significantly higher than those in benign gastric cancer group [(2.26 ± 1.15) ng/L,(3.24 ± 1.47) ng/ml,and (3.75 ± 1.69) U/ml],and normal control group [(1.83 ± 0.92) mg/L,(2.71 ± 1.54) ng/ml,and (3.13 ± 1.82) U/ml] (P ＜ 0.05).FAS,CEA,and CA72-4 levels in patients with lymph node metastasis of gastric cancer [(13.58 ± 6.09) mg/L,(6.25 ± 11.54) ng/ml,and (41.31 ± 13.67) U/ml] were significantly higher than those without lymph node metastasis [(9.21 ± 5.42) mg/L,(28.38 ± 9.72) ng/ml,and (26.75 ± 11.86) U/ml] (P ＜ 0.05).The sensitivity of FAS,CEA,and CA72-4 in patients with gastric cancer was significantly lower than that in combined detection,the specificity of FAS,CEA,and CA72-4 in patients with gastric cancer was significantly higher than that in combination test (P ＜ 0.05).The sensitivity of FAS,CEA,and CA72-4 in patients with lymph node metastasis was significantly lower than that in combination test,and the specificity of FAS,CEA and CA72-4 was significantly higher than that of combined detection (P ＜ 0.05).Conclusions FAS,CEA,and CA72-4 can be used as indicators of gastric cancer and diagnosis of lymph node metastasis.Combined detection of three indexes can improve the diagnostic sensitivity and have good clinical significance.

Dietary phytic acid prevents fatty liver by reducing expression of hepatic lipogenic enzymes and modulates gut microflora in rats fed a high-sucrose diet.

OBJECTIVES: The aim of this study was to investigate the effect of phytic acid (PA) on fatty liver and gut microflora in rats fed a high-sucrose (HSC) diet. METHODS: Three groups of rats were fed a high-starch (HSR) diet or an HSC diet with or without 1.02% sodium PA for 12 d. We evaluated hepatic weight, total lipids, and triacylglycerol (TG) levels, the activities and expression of hepatic lipogenic enzymes (glucose-6-phosphate dehydrogenase, malic enzyme 1, and fatty acid synthetase), and fecal microflora. RESULTS: The HSC diet significantly increased hepatic total lipids and TG levels, and the activities and expression of the hepatic lipogenic enzymes compared with the HSR diet. These upregulations were clearly suppressed by dietary PA. Consumption of PA elevated the fecal ratio of Lactobacillus spp. and depressed the ratio of Clostridium cocoides, and suppressed the elevation in the ratio of C. leptum induced by the HSC diet. CONCLUSION: This work showed that dietary PA ameliorates sucrose-induced fatty liver through reducing the expression of hepatic lipogenesis genes and modulates gut microflora in rats.

Research on the role of HSP27 and Fas/Fasl in the invasion and metastasis of triple negative breast cancer / 中国肿瘤临床

Objective:To study the relationship between the expression of heat shock protein 27 (HSP27) in triple negative breast cancer (TNBC) and the clinico-pathological indexes of breast cancer, investigate the correlation between HSP27 and the fatty acid syn-thetase (FAS)/fatty acid synthetase ligand (FASL) of the cell apoptosis system in the Fas/Fasl system, and study the role of HSP27 in the invasion and metastasis of TNBC. Methods:The immunohistochemical S-P method was used to detect the expression of HSP27 and (FAS)/(FASL) in 100 TNBS tissue sampres, 100 non-TNBS tissue sampres, and 50 paraneoplastic tissues. This method was also used to analyze the correlations between the expression of HSP27 and the clinical and pathological indexes of TNBC, as well as be-tween the HSP27 expression and FAS/FASL expression. Results: HSP27 expression was significantly higher in TNBC than in the non-TNBC and paraneoplastic tissues (P0.05), whereas HSP27 expres-sion was correlated with lymph node metastasis, number of nodal metastases, and P53 and Ki67 expression (P<0.05). Conclusion:The overexpression of HSP27 and the expression dysregulation of the FAS/FASL system may play a role in promoting TNBC transfer and invasion, cell proliferation, and poor prognosis.

Effects of a nonnutritive sweetener on body adiposity and energy metabolism in mice with diet-induced obesity.

OBJECTIVE: Nonnutritive sweeteners (NNSs) have been studied in terms of their potential roles in type 2 diabetes, obesity, and related metabolic disorders. Several studies have suggested that NNSs have several specific effects on metabolism such as reduced postprandial hyperglycemia and insulin resistance. However, the detailed effects of NNSs on body adiposity and energy metabolism have not been fully elucidated. We investigated the effects of an NNS on energy metabolism in mice with diet-induced obesity (DIO). METHODS: DIO mice were divided into NNS-administered (4% NNS in drinking water), sucrose-administered (33% sucrose in drinking water), and control (normal water) groups. After supplementation for 4 weeks, metabolic parameters, including uncoupling protein (UCP) levels and energy expenditure, were assessed. RESULTS: Sucrose supplementation increased hyperglycemia, body adiposity, and body weight compared to the NNS-administered and control groups (P<0.05 for each). In addition, NNS supplementation decreased hyperglycemia compared to the sucrose-administered group (P<0.05). Interestingly, NNS supplementation increased body adiposity, which was accompanied by hyperinsulinemia, compared to controls (P<0.05 for each). NNS also increased leptin levels in white adipose tissue and triglyceride levels in tissues compared to controls (P<0.05 for each). Notably, compared to controls, NNS supplementation decreased the UCP1 level in brown adipose tissue and decreased O2 consumption in the dark phase. CONCLUSIONS: NNSs may be good sugar substitutes for people with hyperglycemia, but appear to influence energy metabolism in DIO mice.

Development in the study of the correlation between stearoyl-coenzyme A desaturase 1 and cancer progression / 中国肿瘤临床

The curative effect of chemotherapy in malignant tumors has been unsatisfactory because of drug resistance and the toxicity of chemotherapeutic drugs. Extensive studies on the metabolism of tumor cells have been undertaken to determine a novel se-lective antitumor drug. An increasing number of studies have demonstrated the close relation between the malignant behavior of tumor tissues and their specialized energy metabolism. Hyper-lipogenesis is one of the metabolic characteristics of the rapid proliferation of tu-mor cells. Stearoyl-coenzyme A desaturase 1 (SCD1) is a critical enzyme in fatty acid synthesis because it catalyzes the conversion of saturated fatty acids into monounsaturated fatty acids. This enzyme is closely related to obesity, fatty liver disease, insulin resistance, and a series of metabolic syndromes. It is also involved in the occurrence and progression of cancer. Determining the function of SCD1 in malignant tumors would provide a new therapeutic target in chemotherapy.

Androgen (dihydrotestosterone)-mediated regulation of food intake and obesity in female mice.

To better understand how elevated androgen levels regulate food intake and obesity in females, we treated ovariectomized female mice with dihydrotestosterone (DHT) (non-aromatazable androgen), measured food intake and body weight, and evaluated physiological changes in liver function, glucose tolerance, and leptin resistance. Ovariectomized mice were treated with DHT or placebo. Mice were then fed a high fat diet under free-feeding or pair-feeding conditions for 3 months. We found that when DHT-treated ovariectomized mice had free access to food (free-feeding), they had increased food intake and higher body weight compared with control animals. These mice also had a significantly greater accumulation of fat in the liver and exhibited increased fasting glucose, impaired glucose tolerance, and resistance to leptin. However, when these mice were placed on a restricted diet and fed the same caloric amounts as controls (pair-feeding), their body weight increased at the same rate as control animals. This suggests that androgen regulates food intake through altered leptin sensitivity, and this increase of food intake could significantly contribute to an obesity phenotype. In summary, we demonstrated a role for androgen in the regulation of food intake and weight gain in females using a mouse model. This model will be useful to further elucidate the role of elevated androgen in females.

Advancing oleaginous microorganisms to produce lipid via metabolic engineering technology.

With the depletion of global petroleum and its increasing price, biodiesel has been becoming one of the most promising biofuels for global fuels market. Researchers exploit oleaginous microorganisms for biodiesel production due to their short life cycle, less labor required, less affection by venue, and easier to scale up. Many oleaginous microorganisms can accumulate lipids, especially triacylglycerols (TAGs), which are the main materials for biodiesel production. This review is covering the related researches on different oleaginous microorganisms, such as yeast, mold, bacteria and microalgae, which might become the potential oil feedstocks for biodiesel production in the future, showing that biodiesel from oleaginous microorganisms has a great prospect in the development of biomass energy. Microbial oils biosynthesis process includes fatty acid synthesis approach and TAG synthesis approach. In addition, the strategies to increase lipids accumulation via metabolic engineering technology, involving the enhancement of fatty acid synthesis approach, the enhancement of TAG synthesis approach, the regulation of related TAG biosynthesis bypass approaches, the blocking of competing pathways and the multi-gene approach, are discussed in detail. It is suggested that DGAT and ME are the most promising targets for gene transformation, and reducing PEPC activity is observed to be beneficial for lipid production.

Expression and significance of sterol regulatory element binding protein-1c in nonalcoholic fatty liver disease in rats / 第三军医大学学报

0.05) , while at the 4th week significantly increased (P