Fat-to-glucose interconversion by hydrodynamic transfer of two glyoxylate cycle enzyme genes

The glyoxylate cycle, which is well characterized in higher plants and some microorganisms but not in vertebrates, is able to bypass the citric acid cycle to achieve fat-to-carbohydrate interconversion. In this context, the hydrodynamic transfer of two glyoxylate cycle enzymes, such as isocytrate lyase (ICL) and malate synthase (MS), could accomplish the shift of using fat for the synthesis of glucose. Therefore, 20 mice weighing 23.37 ± 0.96 g were hydrodinamically gene transferred by administering into the tail vein a bolus with ICL and MS. After 36 hours, body weight, plasma glucose, respiratory quotient and energy expenditure were measured. The respiratory quotient was increased by gene transfer, which suggests that a higher carbohydrate/lipid ratio is oxidized in such animals. This application could help, if adequate protocols are designed, to induce fat utilization for glucose synthesis, which might be eventually useful to reduce body fat depots in situations of obesity and diabetes

Cardiorespiratory Coupling in Asthmatic Children

The relationship between cardiac and respiratory autonomic control has been suggested to be altered in several respiratory disorders. However, and despite the increasing prevalence of asthma, there are not studies assessing the cardiorespiratory coupling (CRC) with respect to the asthmatic status. Since altered autonomic control has been suggested to play a major role in asthma, in this work overnight CRC was assessed in a group of 67 children who underwent a three-month inhaled corticosteroids treatment. After treatment completion, CRC was reduced (p < 0.005) in the subjects without or with a low risk of asthma, whereas it kept unchanged in those with a worse prognosis, suggesting that an altered interaction between cardiac and respiratory activity might be related with an increased risk of asthma

Heart Rate Variability Analysis Assessment for Asthma Control Stratification

Autonomic nervous system (ANS) has been suggested to play a major role in the pathogenesis of asthma. This hypothesis has motivated large research, revealing a reduced modulation of the heart rate in subjects with uncontrolled asthma, when compared to asthmatics with controlled symptomatology. In this work, we assessed ANS activity through heart rate variability analysis in a group of asthmatics classified attending to the control of their symptoms. This information was later used for training a logistic regression classifier aiming at differentiating between the levels of control in asthmatic patients. The accuracy of the classifier improved when including ANS information (71.77%, versus 64.73% when only clinical parameters were considered), suggesting that ANS assessment could contribute to better non-invasive asthma monitoring

Noninvasive Cardiorespiratory Signals Analysis for Asthma Evolution Monitoring in Preschool Children

OBJECTIVE: Despite its increasing prevalence, diagnosis of asthma in children remains problematic due to their difficulties in producing repeatable spirometric maneuvers. Moreover, low adherence to inhaled corticosteroids (ICS) treatment could result in permanent airway remodeling. The growing interest in a noninvasive and objective way for monitoring asthma, together with the apparent role of autonomic nervous system (ANS) in its pathogenesis, have attracted interest towards heart rate variability (HRV) and cardiorespiratory coupling (CRC) analyses. METHODS: HRV and CRC were analyzed in 70 children who were prescribed ICS treatment due to recurrent obstructive bronchitis. They underwent three different electrocardiogram and respiratory signals recordings, during and after treatment period. After treatment completion, they were followed up during 6 months and classified attending to their current asthma status. RESULTS: Vagal activity, as measured from HRV, and CRC, were reduced after treatment in those children at lower risk of asthma, whereas it kept unchanged in those with a worse prognosis. CONCLUSION: Results suggest that HRV analysis could be useful for the continuous monitoring of ANS anomalies present in asthma, thus contributing to evaluate the evolution of the disease, which is especially challenging in young children. SIGNIFICANCE: Noninvasive ANS assessment using HRV analysis could be useful in the continuous monitoring of asthma in children

High-fat diet feeding alters metabolic response to fasting/non fasting conditions. Effect on caveolin expression and insulin signalling

<p>Abstract</p> <p>Background</p> <p>The effect of food intake on caveolin expression in relation to insulin signalling was studied in skeletal muscle and adipocytes from retroperitoneal (RP) and subcutaneous (SC) adipose tissue, comparing fasted (F) to not fasted (NF) rats that had been fed a control or high-fat (HF) diet for 72 days.</p> <p>Methods</p> <p>Serum glucose was analysed enzymatically and insulin and leptin by ELISA. Caveolins and insulin signalling intermediaries (IR, IRS-1 and 2 and GLUT4) were determined by RT-PCR and western blotting. Caveolin and IR phosphorylation was measured by immunoprecipitation. Data were analysed with Mann-Whitney U test.</p> <p>Results</p> <p>High-fat fed animals showed metabolic alterations and developed obesity and insulin resistance. In skeletal muscle, food intake (NF) induced activation of IR and increased expression of IRS-2 in control animals with normal metabolic response. HF animals became overweight, hyperglycaemic, hyperinsulinemic, hyperleptinemic and showed insulin resistance. In skeletal muscle of these animals, food intake (NF) also induced IRS-2 expression together with IR, although this was not active. Caveolin 3 expression in this tissue was increased by food intake (NF) in animals fed either diet. In RP adipocytes of control animals, food intake (NF) decreased IR and IRS-2 expression but increased that of GLUT4. A similar but less intense response was found in SC adipocytes. Food intake (NF) did not change caveolin expression in RP adipocytes with either diet, but in SC adipocytes of HF animals a reduction was observed. Food intake (NF) decreased caveolin-1 phosphorylation in RP but increased it in SC adipocytes of control animals, whereas it increased caveolin-2 phosphorylation in both types of adipocytes independently of the diet.</p> <p>Conclusions</p> <p>Animals fed a control-diet show a normal response to food intake (NF), with activation of the insulin signalling pathway but without appreciable changes in caveolin expression, except a small increase of caveolin-3 in muscle. Animals fed a high-fat diet develop metabolic changes that result in insulin signalling impairment. In these animals, caveolin expression in muscle and adipocytes seems to be regulated independently of insulin signalling.</p

Estimation of the second ventilatory threshold through ventricular repolarization profile analysis

Under the hypothesis that sympathetic control of ventricular repolarization may change once the second ventilatory threshold (VT2) has been reached, a novel methodology for non-invasive VT2 estimation based on the analysis of the T wave from the electrocardiogram (ECG) is proposed, and potential underlying physiological mechanisms are suggested. 25 volunteers (33.4 ± 5.2 years) underwent an incremental power cycle ergometer test (25 W/minute). During the test, respiratory gas exchange and multi-lead ECG were acquired. The former was employed to determine VT2, used here as a reference, whereas the latter was used to compute the temporal profiles of an index of ventricular repolarization instability (dT) and its low-frequency (LF) oscillations (LFdT). The sudden increases observed in dT and LFdT profiles above an established heart rate threshold were employed to derive VT2 estimates, referred to as VT2dT and VT2LFdT, respectively. Estimation errors of -4.7 ± 25.2 W were obtained when considering VT2dT. Errors were lower than the one-minute power increment of 25 W in 68% of the subjects and lower than 50 W in 89.5% of them. When using VT2LFdT, estimation error was of 15.3 ± 32.4 W. Most of the subjects shared common characteristic dT and LFdT profiles, which could be reflecting changes in the autonomic control of ventricular repolarization before and after reaching VT2. The analysis of ventricular repolarization dynamics during exercise allows non-invasive ECG-based estimation of VT2, possibly in relation to changes in the autonomic control of ventricular electrical activity when VT2 is reached

Interplay of early-life nutritional programming on obesity, inflammation and epigenetic outcomes

The huge health burden accompanying obesity is not only attributable to inadequate dietary and sedentary lifestyle habits, since a predisposing genetic make-up and other putative determinants concerning easier weight gain and fat deposition have been reported. Thus, several investigations aiming to understand energy metabolism and body composition maintenance have been performed considering the participation of perinatal nutritional programming and epigenetic processes as well as inflammation phenomena. The Developmental Origins of Health and Disease hypothesis and inheritance-oriented investigations concerning gene–nutrient interactions on energy homoeostasis and metabolic functions have suggested that inflammation could be not only a comorbidity of obesity but also a cause. There are several examples about the role of nutritional interventions in pregnancy and lactation, such as energetic deprivation, protein restriction and excess fat, which determine a cluster of disorders affecting energy efficiency in the offspring as well as different metabolic pathways, which are mediated by epigenetics encompassing the chromatin information encrypted by DNA methylation patterns, histone covalent modifications and non-coding RNA or microRNA. Epigenetic mechanisms may be boosted or impaired by dietary and environmental factors in the mother, intergenerationally or transiently transmitted, and could be involved in the obesity and inflammation susceptibility in the offspring. The aims currently pursued are the early identification of epigenetic biomarkers concerned in individual's disease susceptibility and the description of protocols for tailored dietary treatments/advice to counterbalance adverse epigenomic events. These approaches will allow diagnosis and prognosis implementation and facilitate therapeutic strategies in a personalised ‘epigenomically modelled’ manner to combat obesity and inflammation