Metabolomic analysis of plasma metabolites that may mediate effects of rye bread on satiety and weight maintenance in postmenopausal women

The evidence of the beneficial health effects of dietary fiber and whole grain consumption is strong, but the underlying mechanisms are not completely understood. Here, we investigate how the consumption of high-fiber rye bread (RB) or white-wheat bread (WB) modifies the plasma metabolomic profiles in postmenopausal women. The study was a randomized crossover trial consisting of 8-wk intervention periods and an 8-wk washout period. The study included 39 postmenopausal women with elevated serum total cholesterol (5.0-8.5 mmol/L) and BMI 20-33 kg/m(2). During the intervention periods, the study breads contributed to least 20% of total energy intake. Two analytical platforms for metabolomics were applied. Lipidomic analysis was performed using ultra performance liquid chromatography coupled to electrospray ionization MS and the other metabolites, including sterols, organic acids, and alcohols, were analyzed by 2-dimensional GC coupled to time-of-flight MS. Altogether, 540 metabolites were profiled. Ribitol (P < 0.001), ribonic acid (P < 0.001), and indoleacetic acid (P < 0.001) increased during the RB consumption period. Ribonic acid correlated positively with tryptophan (r = 0.40; P = 0.003), which is a precursor for the biosynthesis of hunger-depressing serotonin. There were no changes in plasma lipidomic profiles during the RB or WB intervention periods. The results suggest that 8-wk consumption of high-fiber rye bread increases metabolites that might mediate positive effects of rye bread on satiety and weight maintenance.     

Effects of resistance exercise session after oral ingestion of melatonin on physiological and performance responses of adult men

This study investigated the effects of a heavy resistance exercise session (RES) with the oral daytime ingestion of melatonin on the physiological responses and acute performance. In a randomized and double-blind controlled study 10 healthy male subjects undertook an 80 min intensive hypertrophic RES for major muscles of the lower and upper extremities. The subjects were studied on two occasions receiving either melatonin (6 mg) or placebo (6 mg) in random order 60 min before each RES. Blood samples were taken from an antecubital vein both in fasting conditions in the morning and before RES (pre 60 min, pre 0 min), during RES (middle) and after RES (post 0 min, post 15 min, post 30 min, post 60 min). Maximal jumping ability and maximal strength in bench press and squat were measured before and immediately after RES in which there were no differences between the melatonin and placebo groups. The serum melatonin concentration increased significantly (P<0.05–0.001) in the melatonin group following oral ingestion of melatonin and was elevated at every time point after that. The concentration reached a peak value of 1171.3±235.2 pg/ml in 60 min at pre 0. Serum melatonin increased slightly but significantly (P<0.05) also in the placebo group just before RES, in the middle of RES and after RES (post 0, post 15). There were large differences (P<0.01–0.001) in the serum melatonin concentration between the groups at all time points. There were no differences in the growth hormone (GH), testosterone and cortisol peak concentrations at any time points between the groups but the area under the curve of GH during RES (P<0.01) and during the 60 min after RES (P<0.05) was lower in the melatonin condition. In conclusion, the present findings give evidence that oral ingestion of melatonin (6 mg) during daytime with heavy resistance exercise may slightly decrease GH concentrations. On the other hand, it seems that melatonin administration during daytime does not have any acute (1–2 h) effects either on the maximal jumping ability or on the maximal strength.     

Constitutive Ret signaling is protective for dopaminergic cell bodies but not for axonal terminals

Ret is the canonical signaling receptor for glial cell line-derived neurotrophic factor (GDNF), which has been shown to have neuroprotective effects when administered prior to neurotoxic challenge. A missense Meth918Thr mutation causes the constitutive activation of Ret, resulting in multiple endocrine neoplasia type 2 B (MEN2B). To clarify the role of Ret signaling in neuroprotection, we studied the effects of the neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) on the dopaminergic system of mice carrying the MEN2B mutation. We found that MEN2B mice were significantly more resistant to nigral tyrosine hydroxylase (TH)-positive cell loss induced by unilateral striatal 6-OHDA than Wt mice. However, 6-OHDA caused profound dopamine (DA) depletion in the striatum of both MEN2B and Wt mice. Systemic MPTP caused similar DA depletion and a decrease in TH-immunostaining in the striatum of MEN2B and Wt mice. Neither neurotoxin induced a compensatory increase in striatal metabolite/DA ratios in the MEN2B mice, possibly contributing to an increased amphetamine-induced turning behavior observed in behavioral assessments of these mice. Thus, our data suggest that activated Ret protects DA cell bodies in the substantia nigra pars compacta, but does not protect DA axons in the striatum.     

Extragonadal LH/hCG action--not yet time to rewrite textbooks

Gonadotropins are indispensable in both sexes in the regulation of gonadal sex steroid production and gametogenesis. In addition to their well-established classical actions, numerous recent publications have indicated the presence and function of luteinizing hormone/chorionic gonadotropin receptors (LH/hCG-R) in a variety of extragonadal tissues. However, the physiological significance of such effects has remained unclear. We have generated two genetically modified mouse models, one with excessive production of hCG and the other with targeted disruption of LH/hCG-R gene, and used them to address the functions of LH and hCG. Numerous gonadal and extragonadal phenotypes were found in the models with the two extremes of LH/hCG action. However, when the extragonadal effects were scrutinized in greater detail, they all appeared to arise through modification of gonadal function, either through enhanced or inhibited response to LH/hCG stimulation. Hence, further evidence is needed before the extragonadal LH/hCG-R expression can be considered functionally significant.     

Diagnosis and treatment of dyslipidemia are neglected in patients with peripheral artery disease

OBJECTIVE: Our aim was to investigate how dyslipidemia was diagnosed and treated in patients with peripheral artery disease (PAD) in a university vascular clinic. DESIGN: Our analysis included all 1 843 PAD patients (median age 71 years, interquartile range 63-79, M/W 975/868) who attended the clinic in 2002-2003 either for diagnostic angiography or for revascularization. The charts of patients tested for dyslipidemia were reviewed closer. RESULTS: Serum lipids were measured in only 214 PAD patients (11.6%). Of them 37.9% smoked, 59.8% had antihypertensive medication, 35.0% diabetes, and 30.8% a history of coronary heart disease. Mean serum cholesterol concentration was 4.5 mmol/l (SD 1.3), LDL-cholesterol 2.54 (0.48), HDL-cholesterol 1.25 (0.48), and triglycerides 1.62 (0.84). Only 40 patients (19.7%) were using statins, this was increased to 72 (33.6%) after clinic visit. Consequently, 50.0% and 53.2% met the current total cholesterol (<4.5 mmol/l) and LDL-cholesterol (<2.5 mmol/l) goals, respectively. CONCLUSIONS: Dyslipidemia was highly under-diagnosed among PAD patients. Serum lipids were measured only in a minority and among them serum lipid values and the use of hypolipidemic drugs were not optimal according to guidelines.