Dodecanedioic acid overcomes metabolic inflexibility in type 2 diabetic subjects

Metabolically healthy skeletal muscle possesses the ability to switch easily between glucose and fat oxidation in response to homeostatic signals. In type 2 diabetes mellitus and obesity, the skeletal muscle shows a great reduction in this metabolic flexibility. A substrate like dodecanedioic acid (C-12), able to increase skeletal muscle glycogen stores via succinyl-CoA formation, might both postpone the fatigue and increase fatty acid utilization, since it does not affect insulin secretion. In healthy volunteers and in type 2 diabetic subjects, the effect of an oral C-12 load was compared with a glucose or water load during prolonged, moderate-intensity, physical exercise. C-12 metabolism was analyzed by a mathematical model. After C-12, diabetics were able to complete the 2 h of exercise. Nonesterified fatty acids increased both during and after the exercise in the C-12 session. C-12 oxidation provided 14% of total energy expenditure, and the sum of C-12 plus lipids oxidized after the C-12 meal was significantly greater than lipids oxidized after the glucose meal (P < 0.025). The fraction of C-12 that entered the central compartment was 47% of that ingested. During the first phase of the exercise ( approximately 60 min), the mean C-12 clearance from the central compartment toward tissues was 2.57 and 1.30 l/min during the second phase of the exercise. In conclusion, C-12 seems to be a suitable energy substrate during exercise, since it reduces muscle fatigue, is rapidly oxidized, and does not stimulate insulin secretion, which implies that lipolysis is not inhibited as reported after glucose ingestion.     

Evaluation of three varieties ofOpuntia ficus-indica (L.) Miller as hosts of the Cochineal insectDactylopius coccus costa (Homoptera: Dactylopiidae) in a semiarid area of northeastern Mexico

Three varieties of prickly pearOpuntia ficus- indica (Villanueva, Copena, and Jalpa varieties) were evaluated in their capacity to be host of the cochineal insect (Dactylopius coccus Costa) in two localities of northeastern Mexico. The experiment was carried out for two seasons, winter and summer, in 1998. Variables under evaluation were: fresh weight of grana, dry weight of grana, and number of insects. The Villanueva variety showed the highest production for the three variables and there were no differences between the other two varieties. Iturbide locality was superior to Linares for the three variables. Higher production (both dry and fresh weight of grana) was obtained during winter and there were no differences between seasons for number of insects. Figures obtained for the Villanueva variety are slightly higher than those reported in literature for the most productive cochineal areas in Mexico.     

Ghrelin Does Not Influence Gastric Emptying in Obese Subjects

Objective: To evaluate the relationship between fasting plasma concentrations of ghrelin and gastric emptying in obese individuals compared with lean subjects. Research Methods and Procedures: We included 20 obese patients (9 men and 11 women, BMI > 30 kg/m²) and 16 nonobese control subjects (7 men and 9 women, BMI ≤ 25 kg/m²). Gastric emptying of solids (egg sandwich labeled with radionuclide) was measured at 120 minutes with (99m)Tc‐single photon emission computed tomography imaging. Ghrelin and leptin were analyzed by radioimmunoassay and ELISA methods, respectively. Results: The gastric half‐emptying time was similar in obese men and women (67.8 ± 14.79 vs. 66.6 ± 13.56 minutes) but significantly shorter (p < 0.001) than in the control population (men: 88.09 ± 11.72 minutes; women: 97.25 ± 10.31 minutes). Ghrelin levels were significantly lower in obese subjects (131.37 ± 47.67 vs. 306.3 ± 45.52 pg/mL; p < 0.0001 in men and 162.13 ± 32.95 vs. 272.8 ± 47.77 pg/mL; p < 0.0001 in women). A negative correlation between gastric emptying and fasting ghrelin levels was observed only in lean subjects (y = ?0.2391x + 157.9; R² = 0.95). Also, in the lean group, ghrelin was the only significant independent determinant of gastric emptying, explaining 98% of the variance (adjusted R²) in a multiple regression analysis. Discussion: This report shows that, in humans, gastric emptying is faster in obese subjects than in lean controls and that, whereas ghrelin is the best determinant of gastric kinetics in healthy controls, this action is lost in obesity.     

Low 25‐Hydroxyvitamin D Does Not Affect Insulin Sensitivity in Obesity after Bariatric Surgery

Objective: A positive correlation between levels of 25‐hydroxyvitamin D [25(OH)D] and insulin sensitivity has been shown in healthy subjects. We aimed to test the hypothesis that concentration of 25(OH)D influences insulin sensitivity in obesity before and after weight loss. Research Methods and Procedures: We investigated the relation between serum 25(OH)D and insulin sensitivity (estimated by euglycemic‐hyperinsulinemic clamp) in 116 obese women (BMI ≥ 40 kg/m²) evaluated before and 5 and 10 years after biliopancreatic diversion (BPD). Body composition was estimated by the isotope dilution method. Results: Prevalence of hypovitaminosis D was 76% in the obese status and 91% and 89% at 5 and 10 years after BPD, respectively, despite ergocalciferol supplementation. 25(OH)D concentration decreased from 39.2 ± 22.3 in obesity (p = 0.0001) to 27.4 ± 16.4 and 25.1 ± 13.9 nM 5 and 10 years after BPD, respectively. Whole‐body glucose uptake increased from 24.27 ± 4.44 at the baseline to 57.29 ± 11.56 and 57.71 ± 8.41 μmol/kg_{fat free mass} per minute 5 and 10 years after BPD, respectively (p = 0.0001). Predictor of 25(OH)D was fat mass (R² = 0.26, p = 0.0001 in obesity; R² = 0.20, p = 0.02 after BPD). Parathormone correlated with fat mass (R² = 0.19; p = 0.0001) and BMI (R² = 0.053; p = 0.01) and inversely with M value (R² = 0.16; p = 0.0001), but only in obese subjects. Discussion: A high prevalence of hypovitaminosis D was observed in morbid obesity both before and after BPD. Low 25(OH)D did not necessarily imply increased insulin resistance after BPD, a condition where, probably, more powerful determinants of insulin sensitivity overcome the low circulating 25(OH)D levels. However, the present data cannot exclude some kind of influence of vitamin D status on glucose and insulin metabolism.     

Metabolite of tryptophan promoting changes in EEG signal and the oxidative status of the brain

Tryptophan is an essential amino acid precursor of neurotransmitter serotonin and triptamine. During its metabolism, indole‐3‐acetic acid (IAA) is generated; this substance presents both antioxidant and prooxidant effects in different biological systems in addition to hipoglicemic effects. To date, electroencephalography (EEG) has been used to evaluate the temporal effect of several substances in neurotransmission. The goal of this study was to characterize the effect of IAA in the brain by analysing the EEG signal and evaluate the oxidative status by means of biochemical parameters. The EEG was acquired by using a noninvasive method, and the brain electric signal was analysed by advanced digital signal processing techniques to determinate the energy signal filtered in different band frequencies. Furthermore, the oxidative status of the brain was investigated by measuring the activity of antioxidant enzymes and lipid peroxidation as well as blood glucose rates of the animals treated with different doses of IAA. Our results showed the relationship of IAA administration with changes in EEG signals. The oxidative status of the brain was modified by IAA after 14 days of treatment. Copyright © 2014 John Wiley & Sons, Ltd.     

Effects of abasic sites on structural,thermodynamic and kinetic properties of quadruplex structures

Abasic sites represent the most frequent lesion in DNA. Since several events generating abasic sites concern guanines, this damage is particularly important in quadruplex forming G-rich sequences, many of which are believed to be involved in several biological roles. However, the effects of abasic sites in sequences forming quadruplexes have been poorly studied. Here, we investigated the effects of abasic site mimics on structural, thermodynamic and kinetic properties of parallel quadruplexes. Investigation concerned five oligodeoxynucleotides based on the sequence d(TGGGGGT), in which all guanines have been replaced, one at a time, by an abasic site mimic (dS). All sequences preserve their ability to form quadruplexes; however, both spectroscopic and kinetic experiments point to sequence-dependent different effects on the structural flexibility and stability. Sequences d(TSGGGGT) and d(TGGGGST) form quite stable quadruplexes; however, for the other sequences, the introduction of the dS in proximity of the 3′-end decreases the stability more considerably than the 5′-end. Noteworthy, sequence d(TGSGGGT) forms a quadruplex where dS does not hamper the stacking between the G-tetrads adjacent to it. These results strongly argue for the central role of apurinic/apyrimidinic site damages and they encourage the production of further studies to better delineate the consequences of their presence in the biological relevant regions of the genome.     

Acid stress-mediated metabolic shift in Lactobacillus sanfranciscensis LSCE1

Lactobacillus sanfranciscensis LSCE1 was selected as a target organism originating from recurrently refreshed sourdough to study the metabolic rerouting associated with the acid stress exposure during sourdough fermentation. In particular, the acid stress induced a metabolic shift toward overproduction of 3-methylbutanoic and 2-methylbutanoic acids accompanied by reduced sugar consumption and primary carbohydrate metabolite production. The fate of labeled leucine, the role of different nutrients and precursors, and the expression of the genes involved in branched-chain amino acid (BCAA) catabolism were evaluated at pH 3.6 and 5.8. The novel application of the program XCMS to the solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) data allowed accurate separation and quantification of 2-methylbutanoic and 3-methylbutanoic acids, generally reported as a cumulative datum. The metabolites coming from BCAA catabolism increased up to seven times under acid stress. The gene expression analysis confirmed that some genes associated with BCAA catabolism were overexpressed under acid conditions. The experiment with labeled leucine showed that 2-methylbutanoic acid originated also from leucine. While the overproduction of 3-methylbutanoic acid under acid stress can be attributed to the need to maintain redox balance, the rationale for the production of 2-methylbutanoic acid from leucine can be found in a newly proposed biosynthesis pathway leading to 2-methylbutanoic acid and 3 mol of ATP per mol of leucine. Leucine catabolism to 3-methylbutanoic and 2-methylbutanoic acids suggests that the switch from sugar to amino acid catabolism supports growth in L. sanfranciscensis in restricted environments such as sourdough characterized by acid stress and recurrent carbon starvation.