Fatty acid synthesis and oxidation are frequently exacerbated in leukemia cells, and may therefore represent a target for therapeutic intervention. In this work we analyzed the apoptotic and chemo-sensitizing action of the fatty acid oxidation inhibitor etomoxir in human acute myeloid leukemia cells. Etomoxir caused negligible lethality at concentrations up to 100 µM, but efficaciously cooperated to cause apoptosis with the anti-leukemic agent arsenic trioxide (ATO, Trisenox), and with lower efficacy with other anti-tumour drugs (etoposide, cisplatin), in HL60 cells. Etomoxir-ATO cooperation was also observed in NB4 human acute promyelocytic cells, but not in normal (non-tumour) mitogen-stimulated human peripheral blood lymphocytes. Biochemical determinations in HL60 cells indicated that etomoxir (25–200 µM) dose-dependently inhibited mitochondrial respiration while slightly stimulating glycolysis, and only caused marginal alterations in total ATP content and adenine nucleotide pool distribution. In addition, etomoxir caused oxidative stress (increase in intracellular reactive oxygen species accumulation, decrease in reduced glutathione content), as well as pro-apoptotic LKB-1/AMPK pathway activation, all of which may in part explain the chemo-sensitizing capacity of the drug. Etomoxir also cooperated with glycolytic inhibitors (2-deoxy-D-glucose, lonidamine) to induce apoptosis in HL60 cells, but not in NB4 cells. The combined etomoxir plus 2-deoxy-D-glucose treatment did not increase oxidative stress, caused moderate decrease in net ATP content, increased the AMP/ATP ratio with concomitant drop in energy charge, and caused defensive Akt and ERK kinase activation. Apoptosis generation by etomoxir plus 2-deoxy-D-glucose was further increased by co-incubation with ATO, which is apparently explained by the capacity of ATO to attenuate Akt and ERK activation. In summary, co-treatment with etomoxir may represent an interesting strategy to increase the apoptotic efficacy of ATO and (with some limitations) 2-deoxy-D-glucose which, although clinically important anti-tumour agents, exhibit low efficacy in monotherapy.

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Introduction: Omentin-1 might play a role in the pathogenesis of insulin resistance and obesity. The aim of the present study was to evaluate the influence of weight loss after biliopancreatic diversion on serum omentin-1 concentrations. Material and Methods A Caucasian population of 24 morbid obese patients was analyzed before and after 12 months of a biliopancreatic diversion surgery. Biochemical and anthropometric evaluation were realized at basal visit and at 12 months. Body weight, fat mass, waist circumferences, blood pressure, fasting blood glucose, fasting insulin, insulin resistance (HOMA-IR), lipid concentrations and omentin-1 were measured. Results: After bariatric surgery and in both gender groups (males vs. females); BMI, weight, fat mass, waist circumference, blood pressure, glucose , total cholesterol, LDL cholesterol, triglycerides, HOMA-IR and fasting insulin decreased in a statistical manner from basal values. Omentin-1 levels increased after bariatric surgery and in both gender the improvement was similar (males vs. females); (delta: –87.1 ± 19.0 ng/dL; p = 0.02 vs. –93.8 ± 28.1 ng/dL; p = 0.03). In the multiple regression analysis adjusted by age and sex; BMI kg/m² (Beta –0.32: 95% CI –3.98 to –0.12) and insulin UI/L (Beta –0.41: 95% CI –8.38 to –0.16) remained in the model with basal omentin-1 levels as dependent variable. The regression model with post-surgery omentin-1 levels as dependent variable showed as independent variables BMI kg/m² (Beta –0.13: 95% CI –7.69 to –0.09) and insulin UI/L (Beta –0.24: 95% CI –5.69 to –0.08), too. Conclusion: This study showed a significant increase in omentin-1 levels after weight loss secondary biliopancreatic diversion surgery. A weak negative correlation with BMI and basal insulin levels was detected.

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patients with malnutrition on admission had longer LOS, higher mortality rate and urgent hospital readmissions one year after discharge. Patients who present MA or DNE cause an economic cost overrun. A nutritional screening tool is essential for the management and early detection of DRM.

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