Personalizing physical exercise in a computational model of fuel homeostasis.
Ontology highlight
ABSTRACT:
SUBMITTER: Palumbo MC
PROVIDER: S-EPMC5919631 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
Publications
Personalizing physical exercise in a computational model of fuel homeostasis.
Palumbo Maria Concetta MC Morettini Micaela M Tieri Paolo P Diele Fasma F Sacchetti Massimo M Castiglione Filippo F
PLoS computational biology 20180426 4
The beneficial effects of physical activity for the prevention and management of several chronic diseases are widely recognized. Mathematical modeling of the effects of physical exercise in body metabolism and in particular its influence on the control of glucose homeostasis is of primary importance in the development of eHealth monitoring devices for a personalized medicine. Nonetheless, to date only a few mathematical models have been aiming at this specific purpose. We have developed a whole- ...[more]
Similar Datasets
Project description:Dysregulation of brain iron metabolism is one of the pathological features of aging and Alzheimer's disease (AD), a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. While physical inactivity is one of the risk factors for AD and regular exercise improves cognitive function and reduces pathology associated with AD, the underlying mechanisms remain unclear. The purpose of the study is to explore the effect of regular physical exercise on modulation of iron homeostasis in the brain and periphery of the 5xFAD mouse model of AD. By using inductively coupled plasma mass spectrometry and a variety of biochemical techniques, we measured total iron content and level of proteins essential in iron homeostasis in the brain and skeletal muscles of sedentary and exercised mice. Long-term voluntary running induced redistribution of iron resulted in altered iron metabolism and trafficking in the brain and increased iron content in skeletal muscle. Exercise reduced levels of cortical hepcidin, a key regulator of iron homeostasis, coupled with interleukin-6 (IL-6) decrease in cortex and plasma. We propose that regular exercise induces a reduction of hepcidin in the brain, possibly via the IL-6/STAT3/JAK1 pathway. These findings indicate that regular exercise modulates iron homeostasis in both wild-type and AD mice.
| S-EPMC8395833 | biostudies-literature
Project description:OBJECTIVE: We investigated how beta-cell function and insulin sensitivity or resistance are affected by the type of blood sample collected or choice of insulin assay and homeostatis model assessment (HOMA) calculator (http://www.dtu.ox.ac.uk). RESEARCH DESIGN AND METHODS: Insulin was measured using 11 different assays in serum and 1 assay in heparinized plasma. Fasting subjects with normoglycemia (n = 12), pre-diabetes, i.e., impaired fasting glucose or impaired glucose tolerance (n = 18), or type 2 diabetes (n = 67) were recruited. Patients treated with insulin or those who were insulin antibody-positive were excluded. HOMA estimates were calculated using specific insulin (SI) or radioimmunoassay (RIA) calculators (version 2.2). RESULTS: All glucose values were within model (HOMA) limits but not all insulin results, as 4.3% were <20 pmol/l and 1% were >300 pmol/l. beta-Cell function derived from different insulin assays ranged from 67 to 122% (median) for those with normoglycemia (P = 0.026), from 89 to 138% for those with pre-diabetes (P = 0.990), and from 50 to 81% for those with type 2 diabetes (P < 0.0001). Furthermore, insulin resistance ranged from 0.8 to 2.0 (P = 0.0007), from 1.9 to 3.2 (P = 0.842), and from 1.5 to 2.9 (P < 0.0001), respectively. This twofold variation in HOMA estimates from the various insulin assays studied in serum may be significant metabolically. Insulin was 15% lower in heparinized plasma (used in the original HOMA study) compared with serum, which is now more commonly used. beta-Cell function differed by 11% and insulin resistance by 15% when estimates derived from specific insulin were calculated using the RIA rather than the SI calculator. CONCLUSIONS: To enable comparison of HOMA estimates among individuals and different research studies, preanalytical factors and calculator selection should be standardized with insulin assays traceable to an insulin reference method procedure.
| S-EPMC2518363 | biostudies-literature
Project description:Purpose: Mitochondrial diseases (MD) are among the most prevalent neuromuscular disorders. Unfortunately, no curative treatment is yet available. This study analyzed the effects of exercise training in an animal model of respiratory chain complex I deficiency, the Harlequin (Hq) mouse, which replicates the clinical features of this condition. Methods: Male heterozygous Harlequin (Hq/Y) mice were assigned to an "exercise" (n = 10) or a "sedentary" control group (n = 11), with the former being submitted to an 8 week combined exercise training intervention (aerobic + resistance training performed five times/week). Aerobic fitness, grip strength, and balance were assessed at the beginning and at the end of the intervention period in all the Hq mice. Muscle biochemical analyses (with results expressed as percentage of reference data from age/sex-matched sedentary wild-type mice [n = 12]) were performed at the end of the aforementioned period for the assessment of major molecular signaling pathways involved in muscle anabolism (mTOR activation) and mitochondrial biogenesis (proliferator activated receptor gamma co-activator 1α [PGC-1α] levels), and enzyme activity and levels of respiratory chain complexes, and antioxidant enzyme levels. Results: Exercise training resulted in significant improvements in aerobic fitness (-33 ± 13 m and 83 ± 43 m for the difference post- vs. pre-intervention in total distance covered in the treadmill tests in control and exercise group, respectively, p = 0.014) and muscle strength (2 ± 4 g vs. 17 ± 6 g for the difference post vs. pre-intervention, p = 0.037) compared to the control group. Higher levels of ribosomal protein S6 kinase beta-1 phosphorylated at threonine 389 (156 ± 30% vs. 249 ± 30%, p = 0.028) and PGC-1α (82 ± 7% vs. 126 ± 19% p = 0.032) were observed in the exercise-trained mice compared with the control group. A higher activity of respiratory chain complexes I (75 ± 4% vs. 95 ± 6%, p = 0.019), III (79 ± 5% vs. 97 ± 4%, p = 0.031), and V (77 ± 9% vs. 105 ± 9%, p = 0.024) was also found with exercise training. Exercised mice presented with lower catalase levels (204 ± 22% vs. 141 ± 23%, p = 0.036). Conclusion: In a mouse model of MD, a training intervention combining aerobic and resistance exercise increased aerobic fitness and muscle strength, and mild improvements were found for activated signaling pathways involved in muscle mitochondrial biogenesis and anabolism, OXPHOS complex activity, and redox status in muscle tissue.
| S-EPMC6673140 | biostudies-literature
Project description:Stem cells, with their capacity to self-renew and to differentiate to more specialized cell types, play a key role to maintain homeostasis in adult tissues. To investigate how, in the dynamic stochastic environment of a tissue, non-genetic diversity and the precise balance between proliferation and differentiation are achieved, it is necessary to understand the molecular mechanisms of the stem cells in decision making process. By focusing on the impact of stochasticity, we proposed a computational model describing the regulatory circuitry as a tri-stable dynamical system to reveal the mechanism which orchestrate this balance. Our model explains how the distribution of noise in genes, linked to the cell regulatory networks, affects cell decision-making to maintain homeostatic state. The noise effect on tissue homeostasis is achieved by regulating the probability of differentiation and self-renewal through symmetric and/or asymmetric cell divisions. Our model reveals, when mutations due to the replication of DNA in stem cell division, are inevitable, how mutations contribute to either aging gradually or the development of cancer in a short period of time. Furthermore, our model sheds some light on the impact of more complex regulatory networks on the system robustness against perturbations.
| S-EPMC7392222 | biostudies-literature
Project description:Electrochemical impedance spectroscopy (EIS) is an indispensable tool for non-destructive operando characterization of Polymer Electrolyte Fuel Cells (PEFCs). However, in order to interpret the PEFC's impedance response and understand the phenomena revealed by EIS, numerous semi-empirical or purely empirical models are used. In this work, a relatively simple model for PEFC cathode catalyst layers in absence of oxygen has been developed, where all the equivalent circuit parameters have an entire physical meaning. It is based on: (i) experimental quantification of the catalyst layer pore radii, (ii) application of De Levie's analytical formula to calculate the response of a single pore, (iii) approximating the ionomer distribution within every pore, (iv) accounting for the specific adsorption of sulfonate groups and (v) accounting for a small H2 crossover through ~15??m ionomer membranes. The derived model has effectively only 6 independent fitting parameters and each of them has clear physical meaning. It was used to investigate the cathode catalyst layer and the double layer capacitance at the interface between the ionomer/membrane and Pt-electrocatalyst. The model has demonstrated excellent results in fitting and interpretation of the impedance data under different relative humidities. A simple script enabling fitting of impedance data is provided as supporting information.
| S-EPMC5862870 | biostudies-other
Project description:We compared the parameters related to glucose homeostasis, and liver and muscle proteomes in fluorosis-susceptible (A/J; S) and fluorosis-resistant (129P3/J; R) mice in response to fluoride (F) exposure and exercise. Ninety male mice (45 R-mice and 45 S-mice) were randomized into three groups: (SI; RI) No-F, No-Exercise, (SII; RII) 50 ppm F, No-Exercise, (SIII; RIII) 50 ppm F, Exercise. Overall, mean F concentrations in the plasma and femur were significantly higher in R-mice compared with S-mice. In R-mice, exercise resulted in an increase in F accumulation in the femur. In S-mice, the mean plasma glucose level was significantly higher in Group II compared with Groups I and III. There was an increase in liver proteins involved in energy flux and antioxidant enzymes in non-exercise groups (I, II) of S-mice in comparison with the corresponding groups of R-mice. The results also showed a decrease in muscle protein expression in Group I S-mice compared with their R-mice counterparts. In conclusion, the findings suggest an increased state of oxidative stress in fluorosis-susceptible mice that might be exacerbated by the treatment with F. In addition, fluorosis-susceptible mice have plasma glucose levels higher than fluorosis-resistant mice on exposure to F, and this is not affected by exercise.
| S-EPMC8878675 | biostudies-literature
Project description:In mammals, vasopressin (AVP) is released from magnocellular neurons of the hypothalamus when osmotic pressure exceeds a fixed set-point. AVP participates to the hydromineral homeostasis (HH) by controlling water excretion at the level of the kidneys. Our current understanding of the HH and AVP secretion is the result of a vast amount of data collected over the five past decades. This experimental data was collected using a number of systems under different conditions, giving a fragmented view of the components involved in HH.Here, we present a high-level model of the rat HH based on selected published results to predict short-term (hours) to long-term (days) variation of six major homeostatic parameters: (1) the extracellular sodium concentration, (2) the AVP concentration, (3) the intracellular volume, (4) the extracellular volume, (5) the urine volume and (6) the water intake. The simulation generates quantitative predictions like the daily mean of the extracellular sodium concentration (142.2 mmol/L), the AVP concentration, (1.7 pg/ml), the intracellular volume (45.3 ml/100 g body weight--bw), the extracellular volume (22.6 ml/100 g bw), the urine volume (11.8 ml/100 g bw) and the cumulative water intake (18 ml/100 g bw). The simulation also computes the dynamics of all these parameters with a high temporal resolution of one minute. This high resolution predicts the circadian fluctuation of the AVP secretion (5 ± 2 pg/ml) and defines the limits of a restoration and a maintenance phase in the HH (2.1 pg/ml). Moreover, the simulation can predict the action of pharmacological compounds that disrupt the HH. As an example, we tested the action of a diuretic (furosemide) combined with a sodium deficient diet to generate quantitative prediction on the extracellular sodium concentration (134 mmol/L) and the need-induced water intake (20.3 ml/100 g bw). These simulated data are compatible with experimental data (136 ± 3 mmol/L and 17.5 ± 3.5 ml/100 g bw, respectively).The quantitative agreement of the predictions with published experimental data indicates that our simplified model of the HH integrates most of the essential systems to predict realistic physiological values and dynamics under a set of normal and perturbed hydromineral conditions.
| S-EPMC2939538 | biostudies-other
Project description:As an endocrine hormone, vitamin D plays an important role in bone health and calcium homeostasis. Over the past two decades, the non-calcemic effects of vitamin D were extensively examined. Although the effect of vitamin D on beta cell function were known for some time, the effect of vitamin D on glucose and fuel homeostasis has attracted new interest among researchers. Yet, to date, studies remain inconclusive and controversial, in part, due to a lack of understanding of the threshold effects of vitamin D. In this review, a critical examination of interventional trials of vitamin D in prevention of diabetes is provided. Like use of vitamin D for bone loss, the benefits of vitamin D supplementation in diabetes prevention were observed in vitamin D-deficient subjects with serum 25-hydroxyvitamin D < 50 nmol/L (20 ng/mL). The beneficial effect from vitamin D supplementation was not apparent in subjects with serum 25-hydroxyvitamin D > 75 nmol/L (30 ng/mL). Furthermore, no benefit was noted in subjects that achieved serum 25-hydroxyvitamin D > 100 nmol/L (40 ng/mL). Further studies are required to confirm these observations.
| S-EPMC8472505 | biostudies-literature
Project description:Recently, we demonstrated that the hypothalamic S1PR1/STAT3 axis plays a critical role in the control of food consumption and energy expenditure in rodents. Here, we found that reduction of hypothalamic S1PR1 expression occurs in an age-dependent manner, and was associated with defective thermogenic signaling and weight gain. To address the physiological relevance of these findings, we investigated the effects of chronic and acute exercise on the hypothalamic S1PR1/STAT3 axis. Chronic exercise increased S1PR1 expression and STAT3 phosphorylation in the hypothalamus, restoring the anorexigenic and thermogenic signals in middle-aged mice. Acutely, exercise increased sphingosine-1-phosphate (S1P) levels in the cerebrospinal fluid (CSF) of young rats, whereas the administration of CSF from exercised young rats into the hypothalamus of middle-aged rats at rest was sufficient to reduce the food intake. Finally, the intracerebroventricular (ICV) administration of S1PR1 activators, including the bioactive lipid molecule S1P, and pharmacological S1PR1 activator, SEW2871, induced a potent STAT3 phosphorylation and anorexigenic response in middle-aged rats. Overall, these results suggest that hypothalamic S1PR1 is important for the maintenance of energy balance and provide new insights into the mechanism by which exercise controls the anorexigenic and thermogenic signals in the central nervous system during the aging process.
| S-EPMC5310661 | biostudies-literature
Project description:Healthy aging can be promoted by enhanced metabolic fitness and physical capacity. Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome. However, mitochondrial-encoded factors that actively regulate aging are unknown. Here, we report that mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice. MOTS-c can regulate (i) nuclear genes, including those related to metabolism and proteostasis, (ii) skeletal muscle metabolism, and (iii) myoblast adaptation to metabolic stress. We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice. In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation. Our data indicate that aging is regulated by genes encoded in both of our co-evolved mitochondrial and nuclear genomes.
| S-EPMC7817689 | biostudies-literature