Prevalence of elevated serum fatty acid synthase in chronic limb-threatening ischemia.

There are currently no serum-based evaluations that can corroborate the severity of peripheral artery disease (PAD). In this cross-sectional study, we assessed the prevalence of elevated serum fatty acid synthase (cFAS) in patients with chronic limb-threatening ischemia (CLTI) and evaluated the accuracy of its use in detecting this condition. Preoperative fasting serum samples from 87 patients undergoing vascular intervention were collected between October 2014 and September 2016. Median age was 62 years, with 56 (64%) men, and 32 (37%) with CLTI. We found that elevated cFAS content (OR 1.17; 95% CI 1.04-1.31), type 2 diabetes (T2D; OR 5.22; 95% CI 1.77-15.4), and smoking (OR 3.53; 95% CI 1.19-10.5) were independently associated with CLTI and could detect the presence of CLTI with 83% accuracy (95% CI 0.74-0.92). Furthermore, serum FAS content was positively correlated with FAS content in femoral artery plaque in patients with severe PAD ([Formula: see text] = 0.22; P = 0.023). Finally, significantly higher co-localization of FAS and ApoB were observed within lower extremity arterial media (P < .001). Our findings indicate that serum FAS content is a marker for disease severity in patients with PAD, independent of concomitant T2D and smoking, and may play a key role in FAS and ApoB peripheral plaque progression.

Higher Level of Fatty Acid Synthase Enzyme Predicts Lower Rate of Completing Debulking Surgery in Epithelial Ovarian Cancer.

BACKGROUND: The most dominant histopathologic type of ovarian cancer is epithelial ovarian cancer (EOC). Primary debulking surgery determines the treatment success and prognosis of advanced stage EOC. To maintain survival and progression, cancer cells need fatty acid synthase enzyme (FASN). The aim of this study was to evaluate preoperative serum FASN and CA 125 as predictors of primary debulking surgery results in patients with EOC. METHODS: An observational cross-sectional study was performed on consecutive patients who underwent debulking surgery for suspected ovarian cancer at Dr. Hasan Sadikin Hospital Bandung from 2017 to 2019. Before debulking surgery, blood samples were examined for the serum levels of FASN and CA 125 using ELISA. RESULTS: There were 53 patients enrolled in this study. Compared with the optimal debulking surgery group, the significant suboptimal debulking surgery group had significantly lower mean serum levels of FASN (0.46 ± 0.144 vs. 0.36 ± 0.128, p = 0.012) and CA 125 (964.22 ± 1722.5 vs. 264.98 ± 251.8, p = 0.002). The cutoff value was highest for the combination of FASN and CA 125 [410.06, area under the curve (AUC) = 77.5% (95% CI 65.5% to 81.9%, p = 0.001)] than for FASN alone [0.375, AUC = 71.3% (95% CI 56.8% to 85.8%, p = 0.009)] and CA 125 alone [222.5, AUC = 75.3% (95% CI 62.5% to 88.1%, p =0.002)]. CONCLUSION: The serum levelof FASN was correlated with suboptimal debulking surgery.

Signature MicroRNA expression profile is associated with lipid metabolism in African green monkey.

BACKGROUND: Non-human primates (NHPs) are important models of medical research on obesity and cardiovascular diseases. As two of the most commonly used NHPs, cynomolgus macaque (CM) and African green monkey (AGM) own different capacities in lipid metabolism of which the mechanism is unknown. This study investigated the expression profiles of lipid metabolism-related microRNAs (miRNAs) in CM and AGM and their possible roles in controlling lipid metabolism-related gene expression. METHODS: By small RNA deep sequencing, the plasma miRNA expression patterns of CM and AGM were compared. The lipid metabolism-related miRNAs were validated through quantitative reverse-transcription (RT) polymerase chain reaction (PCR). Related-target genes were predicted by TargetScan and validated in Vero cells. RESULTS: Compared to CM, 85 miRNAs were upregulated with over 1.5-fold change in AGM of which 12 miRNAs were related to lipid metabolism. miR-122, miR-9, miR-185, miR-182 exhibited the greatest fold changes(fold changes are 51.2, 3.8, 3.7, 3.3 respectively; all P < 0.01). And 77 miRNAs were downregulated with over 1.5-fold change in AGM of which 3, miR-370, miR-26, miR-128 (fold changes are 9.3, 1.8, 1.7 respectively; all P < 0.05) were related to lipid metabolism. The lipid metabolism-related gene targets were predicted by TargetScan and confirmed in the Vero cells. CONCLUSION: We report for the first time a circulating lipid metabolism-related miRNA profile for CM and AGM, which may add to knowledge of differences between these two non-human primate species and miRNAs' roles in lipid metabolism.

Epigenome-wide profiling of DNA methylation in paired samples of adipose tissue and blood.

Many epigenetic association studies have attempted to identify DNA methylation markers in blood that are able to mirror those in target tissues. Although some have suggested potential utility of surrogate epigenetic markers in blood, few studies have collected data to directly compare DNA methylation across tissues from the same individuals. Here, epigenomic data were collected from adipose tissue and blood in 143 subjects using Illumina HumanMethylation450 BeadChip array. The top axis of epigenome-wide variation differentiates adipose tissue from blood, which is confirmed internally using cross-validation and externally with independent data from the two tissues. We identified 1,285 discordant genes and 1,961 concordant genes between blood and adipose tissue. RNA expression data of the two classes of genes show consistent patterns with those observed in DNA methylation. The discordant genes are enriched in biological functions related to immune response, leukocyte activation or differentiation, and blood coagulation. We distinguish the CpG-specific correlation from the within-subject correlation and emphasize that the magnitude of within-subject correlation does not guarantee the utility of surrogate epigenetic markers. The study reinforces the critical role of DNA methylation in regulating gene expression and cellular phenotypes across tissues, and highlights the caveats of using methylation markers in blood to mirror the corresponding profile in the target tissue.

Influence of breastfeeding on blood-cell transcript-based biomarkers of health in children.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The expression of specific genes in peripheral blood cells (PBCs) may be used as biomarkers of the metabolic status. High levels of expression of CPT1A, SLC27A2, INSR, LEPR, FASN and PPARα in PBCs are indicative of a lower risk for the insulin resistant or dyslipidaemic state associated with obesity in children. Breastfeeding seems to confer protective effects against obesity and its related metabolic problems. WHAT THIS STUDY ADDS: Children who had been breastfed showed higher expression levels of SLC27A2, FASN, PPARα and INSR in PBCs compared with formula-fed subjects. The relationship of the PBC transcript levels of SLC27A2, INSR, FASN and PPARα with insulin resistance and dyslipidaemia may be dependent on the type of infant feeding (breast vs. formula). The transcript levels of the mentioned biomarkers could be useful to distinguish the formula-fed children who are at higher risk of metabolic alterations. BACKGROUND: Blood-cell transcripts have showed to be good biomarkers of metabolic alterations and their use in early detection and prevention of future disorders is promising. OBJECTIVE: This study aimed to examine the relation between previously proposed transcriptional biomarkers of metabolic health (SLC27A2, CPT1A, FASN, PPARα, INSR, LEPR) in peripheral blood cells and the type of infant feeding in a subset of children from the IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants) cohort. SUBJECTS: A total of 237 children aged 2-9 years from eight European countries were studied. RESULTS: Breastfed children showed higher expression levels of SLC27A2, FASN, PPARα and INSR, and lower risk of being overweight and of having high plasma triglyceride levels vs. formula-fed children. Besides, overweight formula-fed children presented higher HOMA-index than overweight breastfed children (1.90 vs. 1.62); however, this negative effect was absent in formula-fed children with high expression of SLC27A2. Moreover, formula-fed children with low expression of SLC27A2, FASN, PPARα and INSR presented higher triglyceride levels than subjects with high expression of these genes (77.7 mg dL(-1) vs. 44.8 mg dL(-1) ). This difference was absent in breastfed children. CONCLUSIONS: Protective effects of breastfeeding are reflected in higher expression levels of SLC27A2, FASN, PPARα and INSR in blood cells. These biomarkers may also serve to discriminate the formula-fed children that are at higher risk of metabolic alterations.

Evaluation of plasma soluble fatty acid synthase levels among Saudi autistic children. Relation to disease severity.

OBJECTIVE: To investigate the role of an apoptotic marker soluble fatty acid synthase (s-Fas) antigen in children with autism and its correlation to disease severity. METHODS: The study was conducted between May 2011 and April 2012 at the Department of Physiology and Autism Research and Treatment Center (ARTC) at King Khalid University Hospital and King Saud University (KSU) in Riyadh, Kingdom of Saudi Arabia. Sixty children were enrolled, 20 as controls, 20 mild, and 20 with severe autism. Plasma samples were analyzed for s-Fas. RESULTS: The levels of s-Fas were significantly higher in autistic children compared with control children (p<0.05). Furthermore, this increase was significantly more pronounced in children with severe autism as compared with mild autism, and there was a positive correlation between s-Fas levels and severe autism (p<0.05). CONCLUSION: The s-Fas level is high in Saudi children with severe autism, and can be considered an indicator of disease severity. These findings may offer a new therapeutic or diagnostic tool for children suffering from severe autism.

Increased serum levels of lipogenic enzymes in patients with severe liver steatosis.

BACKGROUND: Lipid metabolism is altered in subjects with liver steatosis. FAS is a key enzyme in de novo lipogenesis and both FAS gene expression and enzymatic activity are primarily regulated by metabolic signals in the liver. Lipoprotein lipase (LPL), the rate-limiting enzyme for the hydrolysis of core triglycerides, plays a pivotal role in lipid metabolism. This study aims to investigate if circulating levels of FAS and LPL could be clinically associated with liver steatosis. METHODS: In this work, we present data obtained from a subsample of 94 subjects with liver steatosis enrolled by NUTRIEPA study, a nutritional trial in subjects with liver steatosis. Serum levels of FAS protein and LPL activity were evaluated by ELISA test and by a fluorescent method, respectively. The diagnosis and the degree of liver steatosis were based on laboratory and ecographic measurements. Statistical methods included Kruskal-Wallis analysis of variance and Wilcoxon signed-rank test, where appropriate. The χ2 test has been performed to analyse categorical variables. RESULTS: The subjects with severe steatosis had significantly higher serum levels of FAS protein and LPL activity compared to subjects with mild and moderate liver steatosis. Moreover, a positive trend in serum levels of FAS expression from lower to higher degree of steatosis was also detected. CONCLUSIONS: We describe a relationship between human liver steatosis and elevated levels of circulating lipogenic enzymes. Increased serum levels of FAS expression and LPL activity could be considered a marker of severe liver steatosis.

Soluble fatty acid synthase relates to bone biomarkers in prepubertal children.

SUMMARY: Circulating soluble fatty acid synthase (FASN, a key enzyme in de novo biosynthesis of fatty acids, expressed in both adipocytes and osteoblasts) is clinically related to a less favorable bone profile in healthy prepubertal children. Soluble FASN may participate in the reciprocal regulation between fat and bone metabolism. INTRODUCTION: Fatty acid synthase (FASN), a key enzyme in de novo biosynthesis of fatty acids, is expressed in adipocytes and osteoblasts. We hypothesized that FASN may participate in the crosstalk between fat and bone. To this aim, we studied the relation between circulating soluble FASN (an extracellular FASN that reflects previously intracellular enzymatic activity) and adipose tissue and bone biomarkers in prepubertal children. METHODS: Circulating soluble FASN, total and high molecular weight (HMW) adiponectin, bone biomarkers [osteocalcin (OC), uncarboxylated osteocalcin (ucOC), C-terminal cross-linked telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (BSAP)], and a profile of energy metabolism [body fat, insulin resistance and secretion (HOMA), serum lipids] were assessed in 84 asymptomatic prepubertal children (44 girls, 40 boys, age 6.8 ± 0.1 year). Serum 25-OH Vitamin D (Vit D) was additionally measured. RESULTS: Circulating soluble FASN increased with increasing HMW adiponectin (r = 0.29, p = 0.01) and decreasing serum Vit D (r = -0.21, p < 0.05), and was related to a less favorable bone profile, showing negative associations with bone-derived metabolic parameters [total OC (r = -0.33, p = 0.002) and ucOC (r = -0.37, p < 0.0001)] and a positive association with the CTX-to-BSAP ratio (r = 0.31, p < 0.01). These correlations were not explained by age, gender, body fat, insulin resistance or secretion or serum lipids; however, they were predominant in those subjects with Vit D levels below the population median. CONCLUSIONS: Circulating soluble FASN relates to both adipose tissue and bone biomarkers in prepubertal children, with associations that are dependent on Vit D concentrations. These findings suggest that FASN may participate in the crosstalk between fat and bone metabolism.

Serum levels of fatty acid synthase in colorectal cancer patients are associated with tumor stage.

PURPOSE: Fatty acid synthase is a common phenotype to various human cancers including those of prostate, colon, lung, endometrium, and stomach. Increased fatty acid synthase levels have been detected in serum from patients with breast and pancreatic cancer. In this study, serum levels of fatty acid synthase were measured in colorectal cancer patients at different stages of disease. METHODS: Consecutive 67 patients with colorectal cancer were enrolled in the study. Serum levels of fatty acid synthase were examined by ELISA test. The Kruskal-Wallis test and the χ (2) method for trend have been used to analyze data. RESULTS: Serum fatty acid synthase levels of patients belonging to three groups of stage disease are statistically different. The patients with stage III and IV have significantly higher serum levels of fatty acid synthase than patients with stage I-II. There is a positive trend in serum fatty acid synthase levels from stage I-II to stage III and IV of disease. CONCLUSIONS: Fatty acid synthase levels are associated with the stage of disease in patients with colorectal cancer.

Serum fatty acid synthase concentration is increased in patients with hepatitis viral infection and may assist in the prediction of liver steatosis.

BACKGROUND: Liver steatosis is frequent in patients with chronic hepatitis viral infections. Intracellular fatty acid synthase (FASN) seems to play a substantial role in its pathogenesis. FASN can also be found in circulation and is significantly increased in HIV-infected individuals, especially if they are co-infected with hepatitis C virus (HCV). OBJECTIVES: To assess whether serum FASN concentration is also increased in patients with chronic hepatitis viral infections and its relationship with liver steatosis. STUDY DESIGN: Samples and associated data were obtained from stored collections in our institutions from patients with chronic infections with either hepatitis B virus (HBV, cHB, n=60), HCV (cHC, n=81) or co-infection (n=29). RESULTS: The incidence of liver steatosis was significantly (p<0.001) different among groups (23.7% in cHB, 34.2% in cHC and 69.2% in co-infected). A similar trend was observed for changes in serum ALT [in µKat/L, 1.41 (0.08), 1.62 (0.08) and 1.95 (0.16) respectively; p=0.02] and serum FASN [in ng/mL, 9.44 (1.28), 16.38 (1.93) and 31.47 (4.26) respectively; p<0.001]. Serum FASN concentration was related to the degree of liver steatosis, and was correlated with serum ALT values when the whole group was considered (ρ=0.207; p=0.007). CONCLUSIONS: Serum FASN concentration is significantly increased in patients with chronic hepatitis viral infections and correlated with the degree of liver steatosis. These findings may represent a basis for further studies searching non-invasive biomarkers with either diagnostic or prognostic value.