Is Serum BDNF Altered in Acute, Short- and Long-Term Recovered Restrictive Type Anorexia Nervosa?

Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in the regulation of food intake and body weight, has been implicated in the development and maintenance of Anorexia nervosa (AN). The majority of previous studies reported lower BDNF levels in acutely underweight AN patients (acAN) and increasing levels after weight rehabilitation. Here, we investigated serum BDNF concentrations in the largest known AN sample to date, both before and after weight restoration therapy. Serum BDNF was measured in 259 female volunteers: 77 in-patient acAN participants of the restrictive type (47 reassessed after short-term weight rehabilitation), 62 individuals long-term recovered from AN, and 120 healthy controls. We validated our findings in a post-hoc mega-analysis in which we reanalyzed combined data from the current sample and those from our previous study on BDNF in AN (combined sample: 389 participants). All analyses carefully accounted for known determinants of BDNF (age, sex, storage time of blood samples). We further assessed relationships with relevant clinical variables (body-mass-index, physical activity, symptoms). Contrary to our hypotheses, we found zero significant differences in either cross-sectional or longitudinal comparisons and no significant relationships with clinical variables. Together, our study suggests that BDNF may not be a reliable state- or trait-marker in AN after all

SCD1 Inhibition Causes Cancer Cell Death by Depleting Mono-Unsaturated Fatty Acids

Increased metabolism is a requirement for tumor cell proliferation. To understand the dependence of tumor cells on fatty acid metabolism, we evaluated various nodes of the fatty acid synthesis pathway. Using RNAi we have demonstrated that depletion of fatty-acid synthesis pathway enzymes SCD1, FASN, or ACC1 in HCT116 colon cancer cells results in cytotoxicity that is reversible by addition of exogenous fatty acids. This conditional phenotype is most pronounced when SCD1 is depleted. We used this fatty-acid rescue strategy to characterize several small-molecule inhibitors of fatty acid synthesis, including identification of TOFA as a potent SCD1 inhibitor, representing a previously undescribed activity for this compound. Reference FASN and ACC inhibitors show cytotoxicity that is less pronounced than that of TOFA, and fatty-acid rescue profiles consistent with their proposed enzyme targets. Two reference SCD1 inhibitors show low-nanomolar cytotoxicity that is offset by at least two orders of magnitude by exogenous oleate. One of these inhibitors slows growth of HCT116 xenograft tumors. Our data outline an effective strategy for interrogation of on-mechanism potency and pathway-node-specificity of fatty acid synthesis inhibitors, establish an unambiguous link between fatty acid synthesis and cancer cell survival, and point toward SCD1 as a key target in this pathway

Spectroscopic Evidence for an Oxazolone Structure in Anionic b-Type Peptide Fragments

Infrared spectra of anionic b-type fragments generated by collision induced dissociation (CID) from deprotonated peptides are reported. Spectra of the b2 fragments of deprotonated AlaAlaAla and AlaTyrAla have been recorded over the 800–1800 cm–1 spectral range by multiple-photon dissociation (MPD) spectroscopy using an FTICR mass spectrometer in combination with the free electron laser FELIX. Structural characterization of the b-type fragments is accomplished by comparison with density functional theory calculated spectra at the B3LYP/6-31++G(d,p) level for different isomeric structures. Although diketopiperazine structures represent the energetically lowest isomers, the IR spectra suggest an oxazolone structure for the b2 fragments of both peptides. Deprotonation is shown to occur on the oxazolone α-carbon, which leads to a conjugated structure in which the negative charge is practically delocalized over the entire oxazolone ring, providing enhanced gas-phase stability