Fatty Acid Synthase Gene Expression Research Articles

Influence of static magnetic field exposure on fatty acid composition in Salmonella Hadar

We have been interested, in this work, to investigate the effect of the exposure to static magnetic field at 200mT (SMF) on the fatty acid (FA) composition of Salmonella enterica subsp Enterica serovar Hadar isolate 287: effects on the proportion of saturated and unsaturated fatty acids (SFAs, UFAs), cyclopropane fatty acids (CFAs) and hydroxy fatty acids after exposure to the static magnetic field at 200mT (SMF). Analysis with Gas Chromatography-Mass Spectrometry (GC-MS) of total lipid showed that the proportion of the most fatty acids was clearly affected. The comparison of UFAs/SFAs ratio in exposed bacteria and controls showed a diminution after 3 and 6h of exposure. This ration reached a balance after 9h of treatment with SMF. So we can conclude that S. Hadar tries to adapt to magnetic stress by changing the proportions of SFAs and UFAs over time to maintain an equilibrium after 9h of exposure, thus to maintain the inner membranes fluidity. Also, a decrease in the proportion of hydroxy FAs was observed after 6h but an increase of this proportion after 9h of exposure. Concerning CFAs, its proportion raised after 6h of exposure to the SMF but it decreased after 9h of exposure. These results are strongly correlated with those of cfa (cyclopropane fatty acid synthase) gene expression which showed a decrease of its expression after 9h of exposure.

Effect of Curcumin on Fatty Acid Synthase Expression and Enzyme Activity in Breast Cancer Cell Line SKBR3

Background: Fatty acid synthase is a multifunctional protein that catalyzes de novo synthesis of long-chain fatty acids. FASN expression is higher in HER2-positive cells, such as SKBR3 and MCF-7/HER2 cells, than in MCF-7 cells, which express lower HER2 levels. Curcumin, a yellow-colored hydrophobic polyphenol derived from the rhizome turmeric, significantly suppressed growth of human breast cancer cells. In this study, we assessed the effect of curcumin on expression and activity of fatty acid synthase in SK-BR-3 breast cancer cells. Objectives: In this study, we decided to determine the effects of Curcumin on Fatty Acid Synthase expression and enzyme activity in breast cancer cell line SKBR3. Methods: We assessed the cytotoxicity effect of curcumin in SK-BR-3 cells by MTT. Apoptosis was performed by flow cytometry. FAS activity was measured by a spectrophotometer at 340 nm of NADPH absorption. Fatty acid synthase gene expression was analyzed by real-time PCR. Results: Curcumin could decrease cell viability and induce apoptosis in SK-BR-3 cells. Curcumin also reduces the enzyme activity and expression of fatty acid synthase. Conclusions: It is possible that inhibitory effects of curcumin on FAS may induce apoptosis in SK-BR-3 breast cancer cells.

Inhibitory effect of emodin on fatty acid synthase, colon cancer proliferation and apoptosis.

Fatty acid synthase (FASN) is a key anabolic enzyme for de novo fatty acid synthesis, which is important in the development of colon carcinoma. The high expression of FASN is considered a promising molecular target for colon cancer therapy. Emodin, a naturally occurring anthraquinone, exhibits an anticancer effect in various types of human cancer, including colon cancer; however, the molecular mechanisms remain to be fully elucidated. Cell viability was evaluated using a Cell Counting Kit-8 assay. The apoptosis rate of cells was quantified via flow cytometry following Annexin V/propidium iodide staining. FASN activity was measured by monitoring oxidation of nicotinamide adenine dinucleotide phosphate at a wavelength of 340 nm, and intracellular free fatty acid levels were detected using a Free Fatty Acid Quantification kit. Western blot analysis and reverse transcription-polymerase chain reaction were used to detect target gene and protein expression. The present study was performed to investigate whether the gene expression of FASN and its enzymatic activity are regulated by emodin in a human colon cancer cell line. Emodin markedly inhibited the proliferation of HCT116 cells and a higher protein level of FASN was expressed, compared with that in SW480, SNU-C2A or SNU-C5 cells. Emodin significantly downregulated the protein expression of FASN in HCT116 cells, which was caused by protein degradation due to elevated protein ubiquitination. Emodin also inhibited intracellular FASN enzymatic activity and reduced the levels of intracellular free fatty acids. Emodin enhanced antiproliferation and apoptosis in a dose- and time-dependent manner. The combined treatment of emodin and cerulenin, a commercial FASN inhibitor, had an additive effect on these activities. Palmitate, the final product of the FASN reaction, rescued emodin-induced viability and apoptosis. In addition, emodin altered FASN-involved signaling pathways, including phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinases/extracellular signal-regulated kinases 1/2. These results suggested that emodin-regulated cell growth and apoptosis were mediated by inhibiting FASN and provide a molecular basis for colon cancer therapy.

Dietary whole and cracked linseed increases the proportion of oleic and α-linolenic acids in adipose tissues and decreases stearoyl-coenzyme A desaturase, acetyl-coenzyme A carboxylase, and fatty acid synthase gene expression in the longissimus thoracis muscle of Yanbian Yellow cattle

We hypothesized that supplementation of linseed in a beef cattle fattening diet would increase PUFA concentrations in intramuscular adipose tissue and depress (), (), and () gene expression by decreasing () expression. Conversely, supplemental linseed would upregulate expression of () and () in muscle of Yanbian Yellow steers. Thirty steers were assigned at random to 3 groups of 10 steers fed either the basal diet (corn grain and corn silage-based commercial concentrate [CON]), the CON diet plus 8% whole linseed (WLS; DM basis), or the CON diet plus 8% cracked linseed (CLS; DM basis) for 6 mo. The WLS and CLS supplements did not affect carcass weight, backfat thickness, or marbling scores ( > 0.10) but increased rib eye area and fat color (more yellow; < 0.05). The WLS and CLS diets decreased the proportions of 16:0 and 18:0 and increased the proportions of 18:1-9, 18:3-3, -9, -11 conjugated linoleic acid, total MUFA, and total PUFA in intramuscular, intermuscular, and subcutaneous adipose tissues. The WLS and CLS diets increased and gene expression whereas the supplements depressed , , , and gene expression in longissimus thoracis muscle, relative to CON muscle, consistent with our hypothesis. Because the WLS and CLS treatments did not affect any measure of carcass adiposity, these results indicated that linseed supplements promoted uptake of dietary lipids while concurrently depressing de novo fatty acid biosynthesis in adipose tissue.

Dietary whole and cracked linseed increases the proportion of oleic and α-linolenic acids in adipose tissues and decreases stearoyl-coenzyme A desaturase, acetyl-coenzyme A carboxylase, and fatty acid synthase gene expression in the longissimus thoracis muscle of Yanbian Yellow cattle

Dietary whole and cracked linseed increases the proportion of oleic and α-linolenic acids in adipose tissues and decreases stearoyl-coenzyme A desaturase, acetyl-coenzyme A carboxylase, and fatty acid synthase gene expression in the longissimus thoracis muscle of Yanbian Yellow cattle

Anti-Cancer Activity of Methanol Extracts of Cichorium Intybus on Human Breast Cancer SKBR3 Cell Line

Abstract Background: Breast cancer is themost prevalent cancer and the second cause of death among women around the world. Inmany cancers, including breast cancer, Fatty acid synthase (FASN) gene expression is increased significantly. In breast cancer cell lines, expression of FASN is higher in HER2 positive cell line like SKBR3 than the others. FASN is the key enzyme for fatty acid synthesis de novo pathway and it is producing palmitate which is necessary for cellmembrane formation. Cichoriumintybus is amedicinal plant that effectively leads to inhibition of fatty acid synthase and thus reduces the percentage of survival of cancer cell lines. Objectives: The aimof this studywas to evaluate the effect ofmethanol extract of Chicoriumintybus root on percentage of survival in SKBR3 cell line. Methods: Human breast cancer SKBR3 cell line was cultured in DMEM medium. Methanol extract of Cichorium intybus root was extracted and different dilutions (200, 300, 400, 500 and 600g/mL) were added to cell culture. Cell viability was quantitated by MTT assay after 24, 48 and 72 hours. Results: Cichorium intybus could decrease cell viability. The effects of extract on cell viability were observed after 24, 48 and 72 hours on SKBR3 cell line and IC50 was 800, 400 and 300 after 24, 48 and 72 hours of treatment, respectively. Conclusions: Our study shows thatmethanol extract of Cichoriumintybus has cytotoxic effects on tumor cells. This is a pilotwork for further evaluation in the future.

Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer.

Fatty acid synthase (FASN) is a key lipogenic enzyme for de novo fatty acid biosynthesis and a druggable metabolic oncoprotein that is activated in most human cancers. We evaluated whether the HER2-driven lipogenic phenotype might represent a biomarker for sensitivity to pharmacological FASN blockade. A majority of clinically HER2-positive tumors were scored as FASN overexpressors in a series of almost 200 patients with invasive breast carcinoma. Re-classification of HER2-positive breast tumors based on FASN gene expression predicted a significantly inferior relapse-free and distant metastasis-free survival in HER2+/FASN+ patients. Notably, non-tumorigenic MCF10A breast epithelial cells engineered to overexpress HER2 upregulated FASN gene expression, and the FASN inhibitor C75 abolished HER2-induced anchorage-independent growth and survival. Furthermore, in the presence of high concentrations of C75, HER2-negative MCF-7 breast cancer cells overexpressing HER2 (MCF-7/HER2) had significantly higher levels of apoptosis than HER2-negative cells. Finally, C75 at non-cytotoxic concentrations significantly reduced the capacity of MCF-7/HER2 cells to form mammospheres, an in vitro indicator of cancer stem-like cells. Collectively, our findings strongly suggest that the HER2-FASN lipogenic axis delineates a group of breast cancer patients that might benefit from treatment with therapeutic regimens containing FASN inhibitors.

Life Long High Fat Diet Causes Hepatic Lipid Accumulation by Programming Lipid Synthesis Genes in Liver of Male Rat

Life long high fat (HF) diet has been shown to cause more hepatic lipid accumulation in offspring as compared to a post‐weaning HF diet. However, it is still unclear what the epigenetic mechanisms are. We hypothesize that a life long HF diet will cause greater hepatic lipid accumulation as compared to a post‐weaning HF diet. The objective of this study is to understand the epigenetic mechanisms of hepatic lipid accumulation as an outcome of life long HF diet. Timed‐pregnant Sprague‐Dawley rats were given either a control (C, 16% fat) or HF (HF, 45% fat) diet during gestation and lactation. Pups from both C and HF mothers were weaned onto the same HF diet, creating two offspring groups: C/HF and HF/HF. Rats were sacrificed at 12 weeks of age and the left lobe of the liver was used for further analysis. Liver histology showed greater hepatic fat accumulation in the HF/HF group. Gene expression data was measured for multiple genes in the following pathways: glycolysis, gluconeogenesis, fatty acid synthesis, and triacylglycerol synthesis. Only glycerol‐3‐phosphate acyltransferase (GPAM) and fatty acid synthase (FASN) showed higher levels of mRNA. DNA methylation of specific genes was analyzed based on data obtained from methyl‐DNA immunoprecipitation with high‐throughput sequencing. Differential methylation was observed for both GPAM and FASN. Our data suggests that life long HF diet increases lipid storage by increased hepatic GPAM and FASN gene expression in male rats, potentially through epigenetic regulation.

Effects of alfalfa flavonoids on broiler performance, meat quality, and gene expression

Two hundred and forty 1-d-old Arbor Acre female broilers were used to study the effects of alfalfa flavonoids (AF) on broiler performance, meat quality, and gene expression. Chicken were fed with basal diet supplemented with AF at 0, 5, 10, or 15 mg kg−1diet for a period of 42 d. Growth performance, meat quality, antioxidant effect and lipoprotein lipase (LPL), adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), and fatty acid synthase (FAS) gene expressions were investigated. Results showed that AF inclusion in the diet enhanced the body weight (BW) at 42 d of age and the average daily gain from 0 to 42 d, decreased the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels and increased HDL level in the serum, enhanced the superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px), and decreased the malondialdehyde (MDA) concentrations in the serum. Also, AF supplementation decreased the abdomen fat rate, marble, and the drip loss and storage loss after the storage for 96 h. Gene expressions’ results showed that AF inclusion decreased the FAS expression and increased the LPL, PPARγ, and ATGL expressions in the liver and adipose tissues, especially when the AF inclusion level was 15 mg kg−1diet. These results indicate that AF were found to be effective for average daily gain and breast percentage promoting, meat quality and antioxidant activity improvement via upregulating the LPL, ATGL, PPARγ, and downregulating the FAS expression in adipose and liver tissues.

Monogalactosyldiacylglycerol: An abundant galactosyllipid of Cirsium brevicaule A. GRAY leaves inhibits the expression of gene encoding fatty acid synthase

BackgroundThe leaves of Cirsium brevicaule A. GRAY (CL) significantly decreased hepatic lipid accumulation and the expression of fatty acid synthase gene (FASN) in mice. PurposeWe aimed to purify and identify the active compound(s) from CL and determine the inhibitory mechanism of expression of FASN. MethodsWe purified monogalactosyldiacylglycerol (MGDG) from extracts of CL (CL-MGDG) and showed that it was the active CL component through analyses of its effects on the expression of genes of human breast cancer cell line, SKBR-3. ResultsThe content and fatty acid composition of CL-MGDG are distinctly different from those of other vegetable-derived MGDGs. Treatment of SKBR-3 cells with MGDG decreased the level of FASN mRNA as well as the levels of mRNA encoding other protein involved in lipogenesis. Further, MGDG treatments significantly inhibited luciferase activities of constructs containing liver X receptor response element in FASN promoter region without altering the levels of mRNA encoding transcription factors. MGDG and the FASN inhibitor C75 decreased the viabilities of SKBR-3 cells in a concentration-dependent manner. CL-MGDG more potently inhibited cell viability than a commercial MGDG preparation. ConclusionsCL represents a good source of glycoglycerolipids with potential as functional ingredients of food.

Genetic diversity analysis of buffalo fatty acid synthase (FASN) gene and its differential expression among bovines

Fatty Acid Synthase (FASN) gene seems to be structurally and functionally different in bovines in view of their distinctive fatty acid synthesis process. Structural variation and differential expression of FASN gene is reported in buffalo (Bubalus bubalis), a bovine species close to cattle, in this study. Amino acid sequence and phylogenetic analysis of functionally important thioesterase (TE) domain of FASN revealed its conserved nature across mammals. Amino acid residues at TE domain, responsible for substrate binding and processing, were found to be invariant in all the mammalian species. A total of seven polymorphic nucleotide sites, including two in coding region of TE domain were identified across the 10 buffalo populations of riverine and swamp types. G and C alleles were found almost fixed at g18996 and g19056 loci, respectively in riverine buffaloes. Principal component analysis of three SNPs (g18433, g18996 and g19056) revealed distinct classification of riverine and swamp buffalo populations. Reverse Transcription-PCR amplification of mRNA corresponding to exon 8–10 region of buffalo FASN helped in identification of two transcript variants; one transcript of 565 nucleotides and another alternate transcript of 207 nucleotides, seems to have arisen through alternative splicing. Both the transcripts were found to be expressed in most of the vital tissues of buffalo with the highest expression in mammary gland. Semi-quantitative and real-time expression analysis across 13 different buffalo tissues revealed its highest expression in lactating mammary gland. When compared, expression of FASN was also found to be higher in liver, adipose and skeletal muscle of buffalo tissues, than cattle. However, the FASN expression was highest in adipose among the three tissues in both the species. Results indicate structural and functional distinctiveness of bovine FASN. Presence of alternate splicing in buffalo FASN also seems to be a unique phenomenon to the bovines, probably associated with mRNA based regulation of the biological functions of FASN in these species.

Association of fatty-acid synthase polymorphisms and expression with outcomes after radical prostatectomy.

Fatty-acid synthase (FASN), selectively overexpressed in prostate cancer (PCa) cells, has been described as linked to the aggressiveness of PCa. Constitutional genetic variation of the FASN gene and the expression levels of FASN protein in cancer cells could thus be expected to predict outcome after radical prostatectomy (RP). This study evaluates the associations of malignant tissue status, neoadjuvant androgen deprivation therapy (NADT) and single-nucleotide polymorphisms (SNPs) of FASN with FASN protein expression in prostate tissue. The study then examines the associations of FASN SNPs and gene expression with three measures of post-prostatectomy outcome. Seven tagging FASN SNPs were genotyped in 659 European American men who underwent RP at Roswell Park Cancer Institute between 1993 and 2005. FASN protein expression was assessed using immunohistochemistry. The patients were followed for an average of 6.9 years (range: 0.1-20.6 years). Outcome was assessed using three end points: biochemical failure, treatment failure and development of distant metastatic PCa. Cox proportional hazards analyses were used to evaluate the associations of the tagging SNPs and FASN expression with these end points. Bivariate associations with outcomes were considered; the associations also were controlled for known aggressiveness indicators. Overall, no SNPs were associated with any known aggressiveness indicators. FASN staining intensity was stronger in malignant than in benign tissue, and NADT was associated with decreased FASN staining in both benign and malignant tissue. The relationships of FASN SNPs and staining intensity with outcome were less clear. One SNP, rs4246444, showed a weak association with outcome. FASN staining intensity also showed a weak and seemingly contradictory relationship with outcome. Additional study with longer follow-up and populations that include more metastatic patients is warranted.

The impact of BMI on outcomes of patients with metastatic renal cell carcinoma treated with targeted therapy: An external validation data set and analysis of underlying biology from The Cancer Genome Atlas.

405 Background: Obesity is a risk factor for renal cell carcinoma (RCC) and a poor prognostic factor across many tumor types. However, reports have suggested that RCC developing in an obesogenic environment may be more indolent. We recently reported on the favorable impact of body mass index (BMI) on survival in the International mRCC Database Consortium (IMDC). The current work aims to externally validate this finding and characterize the underlying biology. Methods: We conducted an analysis of 4,657 metastatic RCC (mRCC) patients (pts) treated on phase II-III clinical trials sponsored by Pfizer from 2003-2013. We assessed the impact of BMI on overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Additionally, we analysed metastatic pts from the clear cell RCC (ccRCC) cohort of TCGA dataset to correlate the expression of Fatty Acid Synthase (FASN) with BMI and OS. Results: At targeted therapy (TT) initiation, 1,829 (39%) pts were normal or underweight (BMI &lt;25 kg/m2) and 2,828 (61%) were overweight or obese (BMI ≥25 kg/m2). Overall, the high BMI group had a longer median OS (23.4 months) than the low BMI group (14.5 months) (hazard ratio (HR) = 0.830, p= 0.0008, 95% CI 0.743-0.925) after adjusting for the IMDC prognostic risk group and other risks factors. In addition, pts with high BMI had improved PFS (HR=0.821, 95% CI 0.746-0.903, p&lt;0.0001) and ORR (odds ratio =1.527, 95% CI 1.258-1.855, p&lt;0.001). These results remain valid when stratified by line of therapy. When stratified by histological subtype, the favorable outcome associated with high BMI was only observed in ccRCC. Toxicity patterns did not differ between BMI groups. In the the Cancer Genome Atlas (TCGA) dataset (n=61), there was a trend towards improved OS in the high BMI group (p=0.07). FASN gene expression inversely correlated with both OS (p=0.002) and BMI (p=0.034). Conclusions: In an external cohort,we validate BMI as an independent prognostic factor for improved survival in mRCC. Given that this finding was observed in ccRCC only, we hypothesize that lipid metabolism may be modulated by the fat laden tumors cells. FASN staining in the IMDC cohort is ongoing to better investigate the obesity paradox in mRCC.

Promoter and first exon methylation regulate porcine FASN gene expression.

DNA methylation is a stable epigenetic mark mediating gene expression. Methylation is crucial for diverse biological processes, including aging and embryo development. FASN (fatty acid synthase) plays an important role in de novo lipogenesis, through catalyzing the reductive synthesis of long-chain fatty acids. In this study, we investigated the FASN gene expression pattern and corresponding DNA methylation status in the inner layer of backfat from Jinhua pigs at different developmental stages. Our results showed that FASN gene expression increases with age and is positively associated with adipocyte volume (r = 0.98, P < 0.01). In addition, the DNA methylation level for the first exon (0.11, CGI 3) of the FASN gene is approximately 8-fold lower than levels for its promoter (0.94, CGI 1&2) (two-way ANOVA, PCGI < 0.01). The association analysis revealed that both promoter (r = -0.944, P < 0.01) and first exon methylation (r = -0.774, P < 0.01) are significantly and negatively correlated with FASN gene expression. Our results will benefit future investigations of the epigenetic mechanism underlying FASN gene expression.

Gene Expression Profiles of Aralkylamine N-Acetyltransferase, B-cell Translocation Gene-2 and Fatty Acid Synthase in Pasture-based Primiparous Holstein-Friesian Dairy Cows Supplemented with Crude Degummed Canola Oil

The effect of oil-rich supplements on the expression of genes involved in lipogenesis and reproduction in pasturebased dairy cows is currently unknown, or at best, scanty and limited to impacts on cow liveweight, body condition score, milk composition, fatty acid and plasma metabolite profiles only. This research investigated the gene expression patterns of Aralkylamine N-acetyltransferase (AANAT), B-cell translocation gene-2 (BTG2) and Fatty Acid Synthase (FASN) genes in response to incremental levels of dietary crude degummed canola oil (CDCO). We tested the hypothesis that the relative mRNA abundance and gene expression profiles of AANAT, BTG2 and FASN in primiparous Holstein-Friesian cows will be up-regulated in response to post-partum dietary supplementation with CDCO in a typical pasture-based dairy production system. Thus, the primary objective of this study was to investigate the expression of AANAT, BTG2 and FASN genes in response to incremental levels of CDCO. A random allocation of primiparous Holstein-Friesian dairy cows into four treatment groups comprising wheat-based pelleted with no supplemental CDCO (control), or with CDCO added at 25 ml kg-1 DM (low), 35 ml kg-1 DM (medium) and 50 ml kg-1 DM (high) was utilized in a ten-week experimental feeding trial including two weeks of adjustment. Both level of supplementation and their interaction with duration were significant sources of variation (P 0.05). The high (0.67 fold), medium (0.87 fold) and low (0.56 fold) treatments had suppressed BTG2 expressions compared to the control (1.0 fold) group. The low expression of BTG2 might be important when the reproductive system of cows is recovering from the effect of gestation and new cell growth is required.

Effects of dietary fat saturation on fatty acid composition and gene transcription in different tissues of Iberian pigs

The effect of two diets, respectively enriched with SFA (S) and PUFA (P), on FA tissue composition and gene expression was studied in fattened Iberian pigs. The FA composition of adipose, muscular and liver tissues was affected by dietary treatment. S group showed higher MUFA and MUFA/SFA ratio and lower PUFA and n−6/n−3 ratio than P group in all analyzed tissues. In muscle and liver the extracted lipids were separated into neutral lipids and polar lipid fractions which showed significantly different responses to the dietary treatment, especially in liver where no significant effect of diet was observed in NL fraction. The expression of six candidate genes related to lipogenesis and FA oxidation was analyzed by qPCR. In liver, stearoyl CoA desaturase (SCD), acetyl CoA carboxylase alpha (ACACA) and malic enzyme 1 (ME1) genes showed higher expression in S group. SCD, ACACA, ME1, and fatty acid synthase (FASN) gene expression levels showed a wide variation across the tested tissues, with much higher expression levels observed in adipose tissue than other tissues. Tissue FA profile and gene expression results support the deposition of dietary FA, the lipogenic effect of dietary saturated fat in liver and the employment of saturated dietary fat for endogenous synthesis of MUFA in all the analyzed tissues.

Flax meal supplementation on the activity of antioxidant enzymes and the expression of oxidative stress- and lipogenic-related genes in dairy cows infused with sunflower oil in the abomasum

The effects of abomasal infusion of sunflower oil (SO) and flax meal (FM) supplementation on activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in blood and mammary tissue and mRNA abundance of oxidative stress- and lipogenic-related genes in mammary tissue of dairy cows were examined. Eight lactating Holstein cows were assigned to a double 4×4 Latin square design with a 2×2 factorial arrangement of treatments: (1) no FM in the diet (CON); (2) diet containing 13.7g/kg FM; (3) no FM in the diet and 250g SO/d infused in the abomasum; and (4) diet containing 13.7g/kg FM and 250g SO/d infused in the abomasum. mRNA abundance of Kappa-B1 in mammary tissue tended to decrease with FM supplementation, while mRNA abundance of SOD2 tended to increase when SO was infused in the absence of FM in the diet. Fatty acid synthase, lipoprotein lipase and stearoyl-coA desaturase gene expression tended to decrease with SO infusion when cows were fed CON. Infusion of SO decreased mRNA abundance of peroxisome proliferator-activated receptorγ1 in mammary tissue of cows fed CON and sterol regulatory element binding transcription factor 1 expression decreased with SO infusion. In conclusion, FM had no effect on oxidative stress-related gene expression in mammary tissue of cows that were infused with SO in the abomasum. Limited effects were observed on mRNA abundance of antioxidant-related genes in mammary tissue whereas abomasal infusion of SO reduced lipogenic-related gene expression.

Fatty acid synthase/oxidized low-density lipoprotein as metabolic oncogenes linking obesity to colon cancer via NF-kappa B in Egyptians

Obesity is a major health problem which heightens the risk of several chronic illnesses including cancer development particularly colon cancer. The underlying pathophysiology of obesity associated colon cancer remains to be elucidated. The purpose of this current study was to determine fatty acid synthase (FASN) activity/expression, oxidized low-density lipoprotein (ox-LDL) level and redox status under the context of anthropometric measurements and lipid profile to find their potential role as interacting biomarkers relating obesity to colon cancer initiation and progression via nuclear factor kappa-B (NF-κB) signaling. This study was conducted upon Egyptian individuals; 30 obese subjects with colon cancer, 11 nonobese and 11 obese subjects without colon cancer. FASN gene expression, NF-κB immunoreactivity, and serum ox-LDL level were estimated by real-time PCR, immunohistochemistry and immunoassay, respectively. FASN activity, glycemic status, obesity, and oxidative stress indices were also assessed. It was found that FASN expression and activity were statistically increased in obese with colon cancer (P=0.021 and 0.018, respectively), with statistically significant increase in patients with advanced grading. Moreover, NF-κB immunoreactivity and serum ox-LDL level were significantly increased in obese colon cancer patients with significantly higher levels in those with advanced grading (all P<0.05). Dyslipidemia, insulin resistance, and oxidative stress indices were worsened in obese patients with colon cancer. These results revealed that FASN and ox-LDL as well as oxidative stress may increase the risk of obesity related colon cancer, particularly via NF-κB signaling and could be used as potential predictive and prognostic biomarkers for obesity complicated with colon cancer.

Aqueous extract of post-fermented tea reverts the hepatic steatosis of hyperlipidemia rat by regulating the lipogenic genes expression and hepatic fatty acid composition.

BackgroundPost-fermented tea has been used for the prevention of metabolic syndrome in Western China. Present study reports the biochemical mechanism of lipid-lowering effects of Jing-wei fu tea (JWFT), a variety of post-fermented tea on high-fat diet-induced hyperglycemia and obesity in rats.MethodsAqueous extract of JWFT was prepared by putting them in boiling water, and then concentrated under reduced pressure. The major compounds of JWFT were determined by high performance liquid chromatography (HPLC). High-fat diet fed rats were orally administered different doses of JWFT aqueous extract (0.5, 1.0 and 2.0 g/kg) for four weeks. At the end of this experiment, hepatic lipids, serum leptin and lipids levels were determined using enzyme-linked immunosorbent assay (ELISA). The hepatic fatty acid composition was analyzed using gas chromatography mass (GC-MS). The relative expression of lipids metabolism genes was analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR).ResultsThe results showed that JWFT inhibited the increase in the body weight, abdominal adipose weight, serum lipids and hepatic lipids, and decreased serum leptin levels of high-fat diet fed rats. JWFT normalized hepatic fatty acid composition of hyperlipidemia rats by up-regulating hepatic acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase 1 (SCD1) and fatty acid synthase (FAS) gene expression, and down-regulating carnitine palmitoyl transferase-1 (CPT1). Furthermore, the results showed that JWFT inhibited the absorption of lipids.ConclusionJWFT could mitigate the obesity-induced hepatic steatosis by regulating hepatic lipogenesis and lipolysis.

The Effects of Choline on Hepatic Lipid Metabolism, Mitochondrial Function and Antioxidative Status in Human Hepatic C3A Cells Exposed to Excessive Energy Substrates

Choline plays a lipotropic role in lipid metabolism as an essential nutrient. In this study, we investigated the effects of choline (5, 35 and 70 μM) on DNA methylation modifications, mRNA expression of the critical genes and their enzyme activities involved in hepatic lipid metabolism, mitochondrial membrane potential (Δψm) and glutathione peroxidase (GSH-Px) in C3A cells exposed to excessive energy substrates (lactate, 10 mM; octanoate, 2 mM and pyruvate, 1 mM; lactate, octanoate and pyruvate-supplemented medium (LOP)). Thirty five micromole or 70 μM choline alone, instead of a low dose (5 μM), reduced hepatocellular triglyceride (TG) accumulation, protected Δψm from decrement and increased GSH-Px activity in C3A cells. The increment of TG accumulation, reactive oxygen species (ROS) production and Δψm disruption were observed under LOP treatment in C3A cells after 72 h of culture, which were counteracted by concomitant treatment of choline (35 μM or 70 μM) partially via reversing the methylation status of the peroxisomal proliferator-activated receptor alpha (PPARα) gene promoter, upregulating PPARα, carnitine palmitoyl transferase-I (CPT-I) and downregulating fatty acid synthase (FAS) gene expression, as well as decreasing FAS activity and increasing CPT-I and GSH-Px activities. These findings provided a novel insight into the lipotropic role of choline as a vital methyl-donor in the intervention of chronic metabolic diseases.