Metabolic Substrate Utilization Research Articles

Synergistic Effects of Salicylic Acid and Bacillus butanolivorans KJ40 for Enhancing Napa Cabbage (Brassica napa subsp. pekinensis) Resilience to Water-Deficit Stress

Climate change exacerbates drought, globally impacting crop production and necessitating the adoption of sustainable strategies. This study investigates the potential synergistic effects of salicylic acid (SA) and Bacillus butanolivorans KJ40 (KJ40) on napa cabbage (Brassica rapa subsp. pekinensis) under water-deficit stress conditions by watering withheld for five days. Results demonstrate that the combined application of KJ40 and SA, particularly at concentrations of 0.5 mM and 1 mM, significantly enhances plant growth and mitigates the negative impacts of water deficit. Moreover, the combination treatment with SA (0.5 mM) and KJ40 (1 × 108 cells/mL) reduces lipid oxidation and enhances antioxidant enzyme activity, indicating improved plant stress tolerance. Analysis of soil microbial profiles reveals alterations in metabolic activity and substrate utilization patterns, suggesting potential changes in rhizosphere dynamics. Additionally, this study examines the impact of SA on KJ40 population dynamics in soil, revealing concentration-dependent effects on bacterial survival. Overall, the combination of KJ40 and SA was effective in mitigating water-deficit stress in napa cabbage. These findings highlight the combination as a novel synergistic strategy to enhance plant resilience to water-deficit stress, offering insights into plant–microbe interactions and soil ecosystem dynamics.

Upregulation of the AMPK-FOXO1-PDK4 pathway is a primary mechanism of pyruvate dehydrogenase activity reduction in tafazzin-deficient cells

Barth syndrome (BTHS) is a rare disorder caused by mutations in the TAFAZZIN gene. Previous studies from both patients and model systems have established metabolic dysregulation as a core component of BTHS pathology. In particular, features such as lactic acidosis, pyruvate dehydrogenase (PDH) deficiency, and aberrant fatty acid and glucose oxidation have been identified. However, the lack of a mechanistic understanding of what causes these conditions in the context of BTHS remains a significant knowledge gap, and this has hindered the development of effective therapeutic strategies for treating the associated metabolic problems. In the current study, we utilized tafazzin-knockout C2C12 mouse myoblasts (TAZ-KO) and cardiac and skeletal muscle tissue from tafazzin-knockout mice to identify an upstream mechanism underlying impaired PDH activity in BTHS. This mechanism centers around robust upregulation of pyruvate dehydrogenase kinase 4 (PDK4), resulting from hyperactivation of AMP-activated protein kinase (AMPK) and subsequent transcriptional upregulation by forkhead box protein O1 (FOXO1). Upregulation of PDK4 in tafazzin-deficient cells causes direct phospho-inhibition of PDH activity accompanied by increased glucose uptake and elevated intracellular glucose concentration. Collectively, our findings provide a novel mechanistic framework whereby impaired tafazzin function ultimately results in robust PDK4 upregulation, leading to impaired PDH activity and likely linked to dysregulated metabolic substrate utilization. This mechanism may underlie previously reported findings of BTHS-associated metabolic dysregulation.

Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure With Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial.

Heart failure triggers a shift in myocardial metabolic substrate utilization, favoring the ketone body 3-hydroxybutyrate as energy source. We hypothesized that 14-day treatment with ketone ester (KE) would improve resting and exercise hemodynamics and exercise capacity in patients with heart failure with reduced ejection fraction. In a randomized, double-blind cross-over study, nondiabetic patients with heart failure with reduced ejection fraction received 14-day KE and 14-day isocaloric non-KE comparator regimens of 4 daily doses separated by a 14-day washout period. After each treatment period, participants underwent right heart catheterization, echocardiography, and blood sampling at plasma trough levels and after dosing. Participants underwent an exercise hemodynamic assessment after a second dosing. The primary end point was resting cardiac output (CO). Secondary end points included resting and exercise pulmonary capillary wedge pressure and peak exercise CO and metabolic equivalents. We included 24 patients with heart failure with reduced ejection fraction (17 men; 65±9 years of age; all White). Resting CO at trough levels was higher after KE compared with isocaloric comparator (5.2±1.1 L/min versus 5.0±1.1 L/min; difference, 0.3 L/min [95% CI, 0.1-0.5), and pulmonary capillary wedge pressure was lower (8±3 mm Hg versus 11±3 mm Hg; difference, -2 mm Hg [95% CI, -4 to -1]). These changes were amplified after KE dosing. Across all exercise intensities, KE treatment was associated with lower mean exercise pulmonary capillary wedge pressure (-3 mm Hg [95% CI, -5 to -1] ) and higher mean CO (0.5 L/min [95% CI, 0.1-0.8]), significantly different at low to moderate steady-state exercise but not at peak. Metabolic equivalents remained similar between treatments. In exploratory analyses, KE treatment was associated with 18% lower NT-proBNP (N-terminal pro-B-type natriuretic peptide; difference, -98 ng/L [95% CI, -185 to -23]), higher left ventricular ejection fraction (37±5 versus 34±5%; P=0.01), and lower left atrial and ventricular volumes. KE treatment for 14 days was associated with higher CO at rest and lower filling pressures, cardiac volumes, and NT-proBNP levels compared with isocaloric comparator. These changes persisted during exercise and were achieved on top of optimal medical therapy. Sustained modulation of circulating ketone bodies is a potential treatment principle in patients with heart failure with reduced ejection fraction. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05161650.

Resting Metabolic Rate and Substrate Utilization during Energy and Protein Availability in Male and Female Athletes.

Active athletes frequently develop low energy (LEA) and protein availabilities (LPA) with consequent changes in the vital metabolic processes, especially resting metabolic rate (RMR) and substrate utilization. This study investigated the association of energy and protein intakes with RMR and substrate utilization in male and female athletes and those with LEA and LPA. Sixty athletes (35% female, 26.83 ± 7.12 y) were enrolled in this study. Anthropometric measurements and body composition analysis were reported to estimate fat-free mass (eFFM). Dietary intakes were recorded by two-day multiple-pass 24 h recall records and three-day food records and then analyzed by food processor software to calculate protein intake (PI) and energy intake (EI). Indirect calorimetry was used to measure RMR and percentages of substrate utilization. Activity-energy expenditure (AEE) was assessed by using an Actighrphy sensor for three days. Energy availability was calculated using the following formula (EA = EI - AEE/eFFM). The correlation of EI and PI with RMR and substrate utilization was tested with Pearson correlation. In the LEA group, both EI and PI correlated positively with RMR (r = 0.308, 0.355, respectively, p < 0.05). In addition, EI showed a positive correlation with the percentage of fat utilization. In the male and sufficient-PA groups, PI correlated positively with the RMR and negatively with the percentage of protein utilization. In conclusion, the percentage of LEA is markedly prevalent in our sample, with a higher prevalence among males. Athletes with LEA had lower fat utilization and lower RMR, while those with sufficient PA showed lower protein utilization with excessive PI. These findings may explain the metabolic responses in the cases of LEA and LPA.

Genomic insights into clostridia in bioenergy production: Comparison of metabolic capabilities and evolutionary relationships.

Bacteria from diverse genera, including Acetivibrio, Bacillus, Cellulosilyticum, Clostridium, Desulfotomaculum, Lachnoclostridium, Moorella, Ruminiclostridium, and Thermoanaerobacterium, have attracted significant attention due to their versatile metabolic capabilities encompassing acetogenic, cellulolytic, and C1-metabolic properties, and acetone-butanol-ethanol fermentation. Despite their biotechnological significance, a comprehensive understanding of clostridial physiology and evolution has remained elusive. This study reports an extensive comparative genomic analysis of 48 fully sequenced bacterial genomes from these genera. Our investigation, encompassing pan-genomic analysis, central carbon metabolism comparison, exploration of general genome features, and in-depth scrutiny of Cluster of Orthologous Groups genes, has established a holistic whole-genome-based phylogenetic framework. We have classified these strains into acetogenic, butanol-producing, cellulolytic, CO2-fixating, chemo(litho/organo)trophic, and heterotrophic categories, often exhibiting overlaps. Key outcomes include the identification of misclassified species and the revelation of insights into metabolic features, energy conservation, substrate utilization, stress responses, and regulatory mechanisms. These findings can provide guidance for the development of efficient microbial systems for sustainable bioenergy production. Furthermore, by addressing fundamental questions regarding genetic relationships, conserved genomic features, pivotal enzymes, and essential genes, this study has also contributed to our comprehension of clostridial biology, evolution, and their shared metabolic potential.

Mitochondrial dynamics and myocardial metabolism alterations during anthracycline-cardiotoxicity

Abstract Background Despite the increased effectiveness of chemotherapeutic agents, cancer represents a lethal illness worldwide and anticancer strategies still present severe adverse effects. Cardiac dysfunction is a dose-dependent common affliction of anthracyclines treatment. Anthracycline-induced cardiotoxicity (AIC) and consequent heart failure has recently been suggested to be mediated by mitochondrial dysfunction; however, the molecular mechanisms driving this connection are incompletely understood. Purpose To study the early molecular changes (before onset of overt heart failure phenotype) related to mitochondrial biology and cardiac metabolism in a mouse model of AIC. Methods CD1 mice underwent 5 weekly i.p. injections (5 mg/kg) of doxorubicin. Cardiac anatomic and functional changes were evaluated by echocardiography at 1, 9 and 15 weeks-after last doxorubicin injection. At each time-point, some animals were sacrificed and hearts were collected for characterisation of mitochondrial dynamics and metabolic substrate utilization by western blot, PCR, immunocytochemistry, high-resolution respirometry, transmission electron microscopy and PET/CT. Results Doxorubicin administration resulted in an early reduction in left ventricle (LV) mass which was the result of marked cardiomyocyte atrophy as early as 1 week after doxorubicin completion. Cardiac atrophy preceded functional abnormalities, which were apparent in the form of reduction in LV ejection fraction at 9 weeks. Mitochondrial dynamics (fusion/fission) and membranes were altered as early as 1 week after doxorubicin completion (i.e. long before changes in LV function). Moreover, mitochondrial respiratory rate was decreased in these animals, together with a decrease in mitochondrial DNA content and biogenesis at early timepoints. Early (1 week) mitochondrial molecular changes were accompanied by altered cardiac metabolism (i.e. switch in substrate utilization to glucose). Conclusions Here we have characterized the dynamics of molecular, anatomical and functional changes during AIC. LV systolic dysfunction is a late phenomenon happening long after molecular and metabolic changes in the heart. Cardiomyocyte atrophy, altered mitochondrial dynamics and respiration, and metabolic switching occur long before overt heart failure phenotype. These early changes appear as promising therapeutic targets to prevent overt AIC and heart failure.

Metabolomic Differences in Connective Tissue Disease-Associated Versus Idiopathic Pulmonary Arterial Hypertension in the PVDOMICS Cohort.

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) experience worse survival and derive less benefit from pulmonary vasodilator therapies than patients with idiopathic PAH (IPAH). We sought to identify differential metabolism in patients with CTD-PAH versus patients with IPAH that might underlie these observed clinical differences. Adult participants with CTD-PAH (n=141) and IPAH (n=165) from the Pulmonary Vascular Disease Phenomics (PVDOMICS) study were included. Detailed clinical phenotyping was performed at cohort enrollment, including broad-based global metabolomic profiling of plasma samples. Participants were followed prospectively for ascertainment of outcomes. Supervised and unsupervised machine learning algorithms and regression models were used to compare CTD-PAH versus IPAH metabolomic profiles and to measure metabolite-phenotype associations and interactions. Gradients across the pulmonary circulation were assessed using paired mixed venous and wedged samples in a subset of 115 participants. Metabolomic profiles distinguished CTD-PAH from IPAH, with patients with CTD-PAH demonstrating aberrant lipid metabolism with lower circulating levels of sex steroid hormones and higher free fatty acids (FAs) and FA intermediates. Acylcholines were taken up by the right ventricular-pulmonary vascular (RV-PV) circulation, particularly in CTD-PAH, while free FAs and acylcarnitines were released. In both PAH subtypes, dysregulated lipid metabolites, among others, were associated with hemodynamic and RV measurements and with transplant-free survival. CTD-PAH is characterized by aberrant lipid metabolism that may signal shifted metabolic substrate utilization. Abnormalities in RV-PV FA metabolism may imply a reduced capacity for mitochondrial beta oxidation within the diseased pulmonary circulation.

To what extent do physiological tolerances determine elevational range limits of mammals?

A key question in biology concerns the extent to which distributional range limits of species are determined by intrinsic limits of physiological tolerance. Here, we use common-garden data for wild rodents to assess whether species with higher elevational range limits typically have higher thermogenic capacities in comparison to closely related lowland species. Among South American leaf-eared mice (genus Phyllotis), mean thermogenic performance is higher in species with higher elevational range limits, but there is little among-species variation in the magnitude of plasticity in this trait. In the North American rodent genus Peromyscus, highland deer mice (Peromyscus maniculatus) have greater thermogenic maximal oxygen uptake ( ) than lowland white-footed mice (Peromyscus leucopus) at a level of hypoxia that matches the upper elevational range limit of the former species. In highland deer mice, the enhanced thermogenic in hypoxia is attributable to a combination of evolved and plastic changes in physiological pathways that govern the transport and utilization of O2 and metabolic substrates. Experiments with Peromyscus mice also demonstrate that exposure to hypoxia during different stages of development elicits plastic changes in cardiorespiratory traits that improve thermogenic via distinct physiological mechanisms. Evolved differences in thermogenic capacity provide clues about why some species are able to persist in higher-elevation habitats that lie slightly beyond the tolerable limits of other species. Such differences in environmental tolerance also suggest why some species might be more vulnerable to climate change than others.

Proteomic analysis of murine kidney proximal tubule sub-segment derived cell lines reveals preferences in mitochondrial pathway activity

The proximal tubule (PT) is a nephron segment that is responsible for the majority of solute and water reabsorption in the kidney. Each of its sub-segments have specialized functions; however, little is known about the genes and proteins that determine the oxidative phosphorylation capacity of the PT sub-segments. This information is critical to understanding kidney function and will provide a comprehensive landscape of renal cell adaptations to injury, physiologic stressors, and development. This study analyzed three immortalized murine renal cell lines (PT S1, S2, and S3 segments) for protein content and compared them to a murine fibroblast cell line. All three proximal tubule cell lines generate ATP predominantly by oxidative phosphorylation while the fibroblast cell line is glycolytic. The proteomic data demonstrates that the most significant difference in proteomic signatures between the cell lines are proteins known to be localized in the nucleus followed by mitochondrial proteins. Mitochondrial metabolic substrate utilization assays were performed using the proximal tubule cell lines to determine substrate utilization kinetics thereby providing a physiologic context to the proteomic dataset. This data will allow researchers to study differences in nephron-specific cell lines, between epithelial and fibroblast cells, and between actively respiring cells and glycolytic cells. SignificanceProteomic analysis of proteins expressed in immortalized murine renal proximal tubule cells was compared to a murine fibroblast cell line proteome. The proximal tubule segment specific cell lines: S1, S2 and S3 are all grown under conditions whereby the cells generate ATP by oxidative phosphorylation while the fibroblast cell line utilizes anaerobic glycolysis for ATP generation. The proteomic studies allow for the following queries: 1) comparisons between the proximal tubule segment specific cell lines, 2) comparisons between polarized epithelia and fibroblasts, 3) comparison between cells employing oxidative phosphorylation versus anaerobic glycolysis and 4) comparisons between cells grown on clear versus opaque membrane supports. The data finds major differences in nuclear protein expression and mitochondrial proteins. This proteomic data set will be an important baseline dataset for investigators who need immortalized renal proximal tubule epithelial cells for their research.

Unravelling the Interplay between Cardiac Metabolism and Heart Regeneration.

Ischemic heart disease (IHD) is the leading cause of heart failure (HF) and is a significant cause of morbidity and mortality globally. An ischemic event induces cardiomyocyte death, and the ability for the adult heart to repair itself is challenged by the limited proliferative capacity of resident cardiomyocytes. Intriguingly, changes in metabolic substrate utilisation at birth coincide with the terminal differentiation and reduced proliferation of cardiomyocytes, which argues for a role of cardiac metabolism in heart regeneration. As such, strategies aimed at modulating this metabolism-proliferation axis could, in theory, promote heart regeneration in the setting of IHD. However, the lack of mechanistic understanding of these cellular processes has made it challenging to develop therapeutic modalities that can effectively promote regeneration. Here, we review the role of metabolic substrates and mitochondria in heart regeneration, and discuss potential targets aimed at promoting cardiomyocyte cell cycle re-entry. While advances in cardiovascular therapies have reduced IHD-related deaths, this has resulted in a substantial increase in HF cases. A comprehensive understanding of the interplay between cardiac metabolism and heart regeneration could facilitate the discovery of novel therapeutic targets to repair the damaged heart and reduce risk of HF in patients with IHD.

The effects of excess salt intake on the kidney metabolism in normal Sprague Dawley rats.

Introduction: This study aimed to determine the effects of a high salt diet upon the metabolism of O 2 and substances in the kidney in normal Sprague Dawley (SD) rats. Methods were developed enabling the intermittent collection of renal arteriovenous (A-Vr) blood and urine samples and to measure renal blood flow (RBF) and arterial pressure (BP) in conscious freely moving rats with GFR determined in a separate group of conscious rats. Other groups were studied to obtain cortical (Cx) and outer medullary (OM) tissue samples for associated transcriptomic and metabolomic profiles. Methods: SD rats were instrumented with a renal arterial ultrasonic flow probe, a femoral arterial and renal venous catheters, and RBF and BP measured continuously (24/7). Arterial (A) and renal venous (Vr) blood and urine were collected repeatedly before and 7, 14, and 21 days after increasing the salt diet from 0.4% (LS) to 4% (HS) NaCl. GFR was measured in age-matched rats and used as control shams for normalization. Blood O 2 content was determined by radiometry. A global metabolomic analysis was performed on plasma and Cx and OM tissue samples at JAX laboratories (Thermo Q-Exactive Orbitrap coupled to Vanquich UPLC system) and together with mRNAseq analysis for Cx and OM by Novogene Inc. Results: BP increased less than 5 mmHg by day 3 of the HS diet while RBF rose nearly 20% (P&lt;0.05) and both were sustained at this level throughout the study. O 2 delivery, O 2 consumption (VO 2 ) and O 2 extraction rose over the 21 days of the HS diet (P&lt;0.05). Total GFR increased from 0.64 to 0.83 mL/min/100 g bw (P&lt;0.05) at HS 7 and remained elevated at HS 21. Whole kidney Na + reabsorption and kidney VO 2 were highly correlated positively (r=0.99). A sparse partial least squares discriminant analysis (sPLS-DA) of metabolomics for each of the 4 modes (C18 +/- and HILIC +/-) revealed clear distinctions between LS, HS14, and HS21 within Cx and OM. The mRNAseq tissue analysis found that the HS diet resulted in reduced expression of genes related to the TCA cycle and metabolism of amino acids and fatty acids. This was consistent with the metabolomic data showing a reduction of tissue citrate and succinate levels. In contrast, glycolysis-related genes including hexokinase, pyruvate kinase and lactate dehydrogenase were upregulated in the Cx tissue by HS. Minimal changes in metabolic pathways were observed in the OM tissue. A-Vr x RBF enabled metabolomic flux determination which showed the release of glucose on LS fed rats which was not evident with the HS diet. Uptake of citrate which was seen on LS was less evident on HS but there was a clear tendency observed for increased release of lactate, pyruvate, and α-ketoglutarate. Conclusions: Normal SD rats fed a HS underwent changes of RBF, O 2 extraction and utilization of metabolic substrates, most notably transitioning ATP production predominantly driven from TCA cycle to non-TCA cycle pathways which we are currently exploring more deeply. HL-116264, HL-151587 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Indirect Calorimetry to Measure Metabolic Rate and Energy Expenditure in Psychiatric Populations: A Systematic Review.

Psychiatric and metabolic disorders are highly comorbid and the relationship between these disorders is bidirectional. The mechanisms underlying the association between psychiatric and metabolic disorders are presently unclear, which warrants investigation into the dynamics of the interplay between metabolism, substrate utilization, and energy expenditure in psychiatric populations, and how these constructs compare to those in healthy controls. Indirect calorimetry (IC) methods are a reliable, minimally invasive means for assessing metabolic rate and substrate utilization in humans. This review synthesizes the extant literature on the use of IC on resting metabolism in psychiatric populations to investigate the interaction between psychiatric and metabolic functioning. Consistently, resting energy expenditures and/or substrate utilization values were significantly different between psychiatric and healthy populations in the studies contained in this review. Furthermore, resting energy expenditure values were systematically overestimated when derived from predictive equations, compared to when measured by IC, in psychiatric populations. High heterogeneity between study populations (e.g., differing diagnoses and drug regimens) and methodologies (e.g., differing posture, time of day, and fasting status at measurement) impeded the synthesis of results. Standardized IC protocols would benefit this line of research by enabling meta-analyses, revealing trends within and between different psychiatric disorders.

Serum lipid profile among Sudanese patients diagnosed with hyperthyroidism

Hyperthyroidism is a term for overactive tissue within the thyroid gland, human hyperthyroidism is accompanied by multiple abnormalities with increased energy expenditure and excessive mobilization and utilization of metabolic substrates. The aim of this study is to investigate the concentration of serum lipid profiles in Sudanese patient with hyperthyroidism in Khartoum state. Analytical case control hospital base study recruited 50 patients diagnosed with hyperthyroidism compare with 50 control group, attended at Military Hospital, Khartoum state from January to April 2021. The results data show that the ages of hyperthyroidism were ranging (20-72 years). TSH and T3 were significantly increased in hyperthyroidism patients compared with control group. T4 on the other hand show no significant difference between hyperthyroidism patients (p=0.353) and control group. Total Cholesterol show significant increase in hyperthyroid patients when compared to control group, while the remaining Lipid profile (triglycerides (T.G), LDL-c HDL-c and VLDL) show no significant increase in hyperthyroidism patients compared to control group, T.G (p= .107), HDL-c (p= .189), and LDL-c (P=.113 ), VLDL-c (P=.506 ).The study show significant positive correlation between the levels of TSH and VLDL (r=0.396, P= 0.004). Positive correlation between the levels of T3 and total cholesterol (r=0.406, P= 0.003), positive correlation between the levels of T3 and LDL-c (r=0.296, P= 0.037). In conclusions, the hyperthyroidism causes significant increases of serum total Cholesterol, and other lipid profile remains normal.

Effect of Exercise on the Resting Metabolic Rate and Substrate Utilization in Women with Gestational Diabetes Mellitus: Results of a Pilot Study.

Regular physical activity during pregnancy has a positive effect on the mother and fetus. However, there is scarce data regarding the effect of exercise in pregnancies complicated by gestational diabetes mellitus (GDM). The aim of the present parallel, non-randomized, open-label, pilot, clinical study was to examine the effect of two exercise programs on the resting metabolic rate (RMR) and substrate utilization in pregnancies complicated by GDM, compared with usual care (advice for the performance of exercise). Forty-three pregnant women diagnosed with GDM between the 24th and 28th gestational week, volunteered to participate. Three groups were formed: Usual care (n = 17), Walking (n = 14), and Mixed Exercise (n = 12). The Usual care group was given advice on maintaining habitual daily activities without any additional exercise. The Walking group exercised regularly by walking, in addition to the habitual daily activities. Finally, the Mixed Exercise group participated in a program combining aerobics and strength exercises. Training intensity was monitored continuously using lightweight, wearable monitoring devices. The Walking and Mixed Exercise groups participated in the training programs after being diagnosed with GDM and maintained them until the last week of gestation. RMR and substrate utilization were analyzed using indirect calorimetry for all participants twice: between 27th and 28th gestational week and as close as possible before delivery. No differences were observed between groups regarding body composition, age, and medical or obstetrical parameters before or after the exercise programs. RMR was increased after the completion of the exercise interventions in both the Walking (p = 0.001) and the Mixed Exercise arms (p = 0.002). In contrast, substrate utilization remained indifferent. In conclusion, regular exercise of moderate intensity (either walking, or a combination of aerobic and strength training) increases RMR in women with GDM compared to the lack of systematic exercise. However, based on the present, pilot data, these exercise regimes do not appear to alter resting substrate utilization.

The Relationship Among Resting Metabolic Rate, RER, Substrate Utilization, And Step Counts In College Students

The Relationship Among Resting Metabolic Rate, RER, Substrate Utilization, And Step Counts In College Students

Regulation of Energy Metabolism by Dietary pH and Protein Source in Diet‐induced Obese Mice and Female Mice

Consumption of foods with acidic pH has been proposed as a potential contributor to negative metabolic health outcomes. Thus, in this work, we determined the main effects of dietary pH during onset of obesity in male and female B6 mice. We hypothesized that metabolic health will be improved by consuming a diet containing pH‐enhanced ground beef or casein diets, compared to a non‐pH‐enhanced diets. To test this hypothesis, we designed a mouse study using the following 8 groups: Low‐fat diet + casein protein (LFC), LF + casein with pH enhanced/ammonia (LFCN), LF + beef protein (LFB), LFB with pH enhanced (LFBN), High‐fat diet + casein protein (HFC), HF + casein with pH enhanced (HFCN), HF + beef protein (HFB) and HFB with pH enhanced (HFBN). Mice were fed these diets for 12 weeks, during which we measured changes in body weight and food intake. Mice were individually placed in metabolic cages (TSE PhenoMaster System) at ambient temperature and a 12‐hour light/dark cycle at week 11. The relationship between metabolic rate and body mass was normalized, and we evaluated energy balance (H), respiratory exchange ratio (RER), VCO2, VO2, feed, drink and distance traveled by the mice. These metabolic data were analyzed in both day and night periods. Blood and tissues were collected at the end of the study and fat pad weights were measured. Results showed that in males, body weight was increased in all HF groups, regardless of the protein source, while females did not exhibit any differences across groups. However, for energy metabolism, overall, females exhibited the main changes, especially for the interaction between LF and HF groups. These findings suggest that despite the lack of significant weight gain in females, they used fat as energy source based on their RER, VCO2 and VO2 data. During the day, only HF females had decreased VCO2, and at night both male and female exhibited the same pattern of decreased VCO2. During the night, only males from HF groups had reduced VO2. Regarding energy intake, only HF females had increased food consumption compared to males. The main effects of RER in both males and females were related to diet (LF x HF), in both day and night periods. Interestingly, females also presented differences for the interactions of the protein content (casein vs beef) during the day (p&lt;0.0115). The latter suggests that in females, the protein source may be related to energy consumption and substrate utilization. Fat pad weights were increased in males from all HF groups compared to all LF groups. However, in females, only HFC groups had higher fat pad weights compared to LFC. The reduced RER, observed in both male and female mice from HF groups indicates that fat was oxidized and used as the main energy source in these groups, consistent with higher dietary fat content. Taken together, our data suggest that metabolic changes and substrate utilization are affected by dietary fat content (HF) and are more pronounced in female mice. Further analyses in metabolically active tissues from these mice will help elucidate the mechanisms mediating sex‐dependent differences in metabolic effects of dietary pH enhancement, fat content and source of protein.

Acute Effects of Whole-Body Vibration on Resting Metabolic Rate and Substrate Utilisation in Healthy Women.

Simple SummaryWhole-body vibration induces a number of physiological responses and is used both in physical training, and in the treatment of patients with various diseases. Whole-body vibration increases blood flow, skin temperature, bone density, muscle strength and affects the functions of the nervous system. The effect of whole-body vibration on metabolism is interesting. It has been suggested that whole-body vibration shifts energy metabolism towards carbohydrate utilisation and that this may increase post-exercise oxygen uptake. Increased resting metabolism (increased energy expenditure) during whole-body vibration may indicate that whole-body vibration can be used as an adjunct to treatment programs for overweight or metabolic disorders.The aim of the study was to determine the acute effects of single-whole-body vibration (WBV) on resting metabolic rate (RMR) and carbohydrate–lipid profile of blood in young, healthy women. The participants, in a randomised controlled crossover study, participated in two trials: WBV and a vibration simulation (placebo). The WBV was performed in the prone position and cycloidal-oscillatory vibration was used. The RMR measurement (calorimetry) was performed: before the WBV, during WBV, immediately after the completion of WBV, and 1 h after the completion of WBV. For biochemical analyses, venous blood was collected. During WBV, there was a significant increase in RMR compared to baseline. Immediately after and 1 h following the end of the WBV, RMR was close to baseline levels (p > 0.05). The increased energy expenditure resulted from the increased utilisation of carbohydrates and proteins during the vibration. In the placebo condition, there were no significant changes over time in the level of the studied indices during calorimetry. The WBV had no significant effects on the level of glucose in the blood. The applied vibration did not significantly affect the concentration of the analysed lipid indices, which were within the physiological norms for all measurements. Results indicate the need for further research to establish the physiological mechanisms underlying the observed effects of WBV on resting metabolic rate.

Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells.

Cardiomyocytes rely on specialised metabolism to meet the high energy demand of the heart. During heart development, metabolism matures and shifts from the predominant utilisation of glycolysis and glutamine oxidation towards lactate and fatty acid oxidation. Iron deficiency (ID) leads to cellular metabolism perturbations. However, the exact alterations in substrate metabolism during ID are poorly defined. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), the present study investigated changes in major metabolic substrate utilisation in the context of ID or upon transferrin rescue. Typically, during hiPSC-CM differentiation, the greatest increase in total metabolic output and rate was seen in fatty acid metabolism. When ID was induced, hiPSC-CMs displayed increased reliance on glycolytic metabolism, and six TCA cycle, five amino acid, and four fatty acid substrates were significantly impaired. Transferrin rescue was able to improve TCA cycle substrate metabolism, but the amino acid and fatty acid metabolism remained perturbed. Replenishing iron stores partially reverses the adverse metabolic changes that occur during ID. Understanding the changes in metabolic substrate utilisation and their modification may provide potential for discovery of new biomarkers and therapeutic targets in cardiovascular diseases.

Abstract 11459: Mitochondrial Metabolites Predict Cardiovascular Outcomes and Heart Failure in Individuals with Type 2 Diabetes Mellitus: An Exscel Biomarker Substudy

Introduction: Metabolic substrate utilization is central to metabolic disease. Metabolic pathways linking type 2 diabetes (T2D) to major adverse cardiac events (MACE) and heart failure (HF) remain poorly understood and T2D drug effects on metabolite biomarkers could improve biological understanding and support precision medicine approaches. Hypothesis: Circulating metabolites characterizing mitochondrial dysfunction are predictors for MACE and hospitalization for HF (hHF), and are improved with exenatide. Methods: We performed targeted mass-spectrometry profiling of 60 metabolites on baseline and 12-month plasma samples from 978 participants from EXSCEL, a randomized trial of the GLP-1 receptor agonist, exenatide. Principal components analysis (PCA) was used; resultant metabolite factors were analyzed with univariate and multivariable logistic regression (adjusted for history of HF, coronary artery disease, BMI, HbA 1c , eGFR, blood pressure) for association with MACE (CV death, non-fatal MI or stroke) and hHF. Results were validated in participants from TECOS, a randomized trial of the DPP-4 inhibitor sitagliptin. Metabolite changes by treatment arm were tested. Results: Of 12 PCA metabolite factors, two nominally associated with MACE in both univariate and multivariable models and two associated with hHF in univariate, but not multivariable models ( Table ). Individual metabolites remained associated with MACE in multivariable models and with hHF in univariate models. Similar results were seen in the TECOS validation cohort. Individual metabolites decreased to a greater extent in exenatide randomized individuals compared with placebo. Conclusions: Metabolites reporting on dysregulated mitochondrial fatty acid oxidation are increased in individuals with T2D who experience MACE. These biomarkers may improve CV risk prediction models, appear to be beneficially modified by exenatide, and highlight emerging risk mechanisms.

Thermoregulatory and Metabolic Demands of Naval Special Warfare Divers During a 6-h Cold-Water Training Dive.

Introduction: Extreme environmental conditions induce changes in metabolic rate and substrate use due to thermoregulation. Cold-water full-body submersion for extended periods of time is inevitable for training and missions carried out by Naval Special Warfare divers. Anthropometric, physiologic, and metabolic data have been reported from partial immersion in cold water in non-thermally protected men; data is limited in thermally protected divers in extremely cold water. Thermoregulatory and metabolic demands during prolonged cold-water submersion in Naval Special Warfare divers are unknown.Objective: Assess thermoregulatory and metabolic demands of Naval Special Warfare divers surrounding prolonged cold-water submersion.Materials and Methods: Sixteen active-duty U.S. Navy Sea Air and Land (SEAL) operators tasked with cold-water dive training participated. Divers donned standard military special operations diving equipment and fully submerged to a depth of ∼ 6 m in a pool chilled to 5°C for a 6-h live training exercise. Metabolic measurements were obtained via indirect calorimetry for 10-min pre-dive and 5-min post dive. Heart rate, skin temperature, and core temperature were measured throughout the dive.Results: Core temperature was maintained at the end of the 6-h dive, 36.8 ± 0.4°C and was not correlated to body composition (body fat percentage, lean body mass) or metabolic rate. SEALs were not at risk for non-freezing cold injuries as mean skin temperature was 28.5 ± 1.6°C at end of the 6-h dive. Metabolic rate (kcal/min) was different pre- to post-dive, increasing from 1.9 ± 0.2 kcal/min to 2.8 ± 0.2 kcal/min, p < 0.001, 95% CI [0.8, 1.3], Cohen’s d effect size 2.3. Post-dive substrate utilization was 57.5% carbohydrate, 0.40 ± 0.16 g/min, and 42.5% fat, 0.13 ± 0.04 g/min.Conclusion: Wetsuits supported effective thermoprotection in conjunction with increase in thermogenesis during a 6-h full submersion dive in 5°C. Core temperature was preserved with an expected decrease in skin temperature. Sustained cold-water diving resulted in a 53% increase in energy expenditure. While all participants increased thermogenesis, there was high inter-individual variability in metabolic rate and substrate utilization. Variability in metabolic demands may be attributable to individual physiologic adjustments due to prior cold exposure patterns of divers. This suggests that variations in metabolic adjustments and habituation to the cold were likely. More work is needed to fully understand inter-individual metabolic variability to prolonged cold-water submersion.