The effects of RB101, a mixed inhibitor of enkephalin-catabolizing enzymes, on carrageenin-induced spinal c-Fos expression are completely blocked by β-funaltrexamine, a selective μ-opioid receptor antagonist

We have demonstrated that pre-administered RB101 (40 mg/kg, i.v.), a mixed inhibitor of enkephalin-catabolizing enzymes, decreased spinal c-Fos expression induced 1 h and 30 min after intraplantar (i.pl.) carrageenin (41% reduction, p<0.01). These effects were completely blocked by pre-administered β-funaltrexamine (10 mg/kg, i.v., 24 h prior to stimulation), a selective long-lasting μ-opioid receptor antagonist. In conclusion, these results clearly demonstrate that the effects of endogenous enkephalins on noxiously evoked spinal c-Fos expression are essentially mediated via μ-opioid receptors.     

Circulating glutamate level as a potential biomarker for abdominal obesity and metabolic risk

Background and aimCirculating level of glutamate, a by-product of the catabolism of branched-chain amino acids, has been positively correlated with visceral adipose tissue accumulation and waist circumference (WC). The aim of the present study was to assess the potential of using glutamate level to identify individuals with abdominal obesity and a high cardiometabolic risk.Methods and resultsThe study sample included 99 men and 99 women. Fasting serum glutamate was measured using the Biocrates p180 kit. Anthropometric and metabolic variables were used to identify individuals with abdominal obesity (WC ≥ 95 cm in both sexes), the hypertriglyceridemic waist (HTW) phenotype and the metabolic syndrome (MetS). Mean (±SD) age was 34.1 ± 10.1 years, mean BMI was 29.0 ± 6.2 kg/m² and mean WC was 92.7 ± 16.5 cm. Glutamate was strongly correlated with WC (r = 0.66 for men; r = 0.76 for women, both p < 0.0001) and multiple markers of metabolic dysfunction, particularly fasting triglyceride level (r = 0.59 for men; r = 0.57 for women, both p < 0.0001), HDL-cholesterol level (r = ?0.45, p < 0.0001 in both sexes) and the HOMA-IR index (r = 0.65 for men; r = 0.60 for women, both p < 0.0001). Logistic regressions showed that glutamate had an excellent accuracy to identify individuals with abdominal obesity (ROC_AUC: 0.90 for both sexes), a good accuracy to identify those with the HTW phenotype (ROC_AUC: 0.82 for men; 0.85 for women) and fair-to-good accuracy for the MetS (ROC_AUC: 0.78 for men; 0.89 for women).ConclusionGlutamate level may represent an interesting potential biomarker of abdominal obesity and metabolic risk.     

BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism

Previously, we have identified the branched chain amino-acid transaminase 1 (BCAT1) gene as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that BCAT1 is strongly overexpressed in both LMP and HG serous epithelial ovarian tumors, which probably correlates with its hypomethylated status. Knockdown of the BCAT1 expression in epithelial ovarian cancer (EOC) cells led to sharp decrease of cell proliferation, migration and invasion and inhibited cell cycle progression. BCAT1 silencing was associated with the suppression of numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, and the induction of some tumor suppressor genes (TSGs). Moreover, BCAT1 suppression resulted in downregulation of numerous genes implicated in lipid production and protein synthesis, suggesting its important role in controlling EOC metabolism. Further metabolomic analyses were indicative for significant depletion of most amino acids and different phospho- and sphingolipids following BCAT1 knockdown. Finally, BCAT1 suppression led to significantly prolonged survival time in xenograft model of advanced peritoneal EOC. Taken together, our findings provide new insights about the functional role of BCAT1 in ovarian carcinogenesis and identify this transaminase as a novel EOC biomarker and putative EOC therapeutic target.