NMR metabolomics study of chronic low-dose exposure to a cocktail of persistent organic pollutants.

Nowadays, exposure to endocrine-disrupting chemicals (EDCs), including persistent organic pollutants (POPs), is one of the most critical threats to public health. EDCs are chemicals that mimic, block, or interfere with hormones in the body's endocrine system and have been associated with a wide range of health issues. This innovative, untargeted metabolomics study investigates chronic low-dose internal exposure to a cocktail of POPs on multiple tissues that are known to accumulate these lipophilic compounds. Interestingly, the metabolic response differs among selected tissues/organs in mice. In the liver, we observed a dynamic effect according to the exposure time and the doses of POPs. In the brain tissue, the situation is the opposite, leading to the conclusion that the presence of POPs immediately gives a saturated effect that is independent of the dose and the duration of exposure studied. By contrast, for the adipose tissues, nearly no effect is observed. This metabolic profiling leads to a holistic and dynamic overview of the main metabolic pathways impacted in lipophilic tissues by a cocktail of POPs.

The effects of pollutant mixture released from grafted adipose tissues on fatty acid and lipid metabolism in the skeletal muscles, kidney, heart, and lungs of male mice.

Persistent organic pollutants (POPs) accumulated in the adipose tissue can affect the fatty acid and lipid metabolism in the body. Gas chromatography-mass spectrometry (GC-MS) metabolomics analysis was carried out to study the metabolic changes induced by internal exposure to the POPs in mouse skeletal muscle (soleus, plantaris, and gastrocnemius), kidney, heart, and lungs. Male donor mice were injected with a mixture of 10 POPs at concentrations of 0 × and 5 × lowest-observed-adverse-effect level (LOAEL). Their adipose tissue (AT) containing the POP was then grafted onto the host mice and the metabolic change of the host mice was monitored for 3 or 21 days. The metabolites related to fatty acid and lipid metabolism were studied. For the host mice engrafted with POP-containing fat pad, there was dysregulation of the fatty acids and glycerides observed in all the organs studied 3 days after the graft. However, there was no longer a significant change in the metabolites 21 days after the graft. The difference in significant values and metabolite regulation in each of the skeletal muscles showed that the POP mixture affects different types of skeletal muscle in a heterogeneous manner. Fold change analysis showed that certain metabolites in the kidney of host mice exposed to POPs for 3 days were greatly affected. Using multivariate analysis, apart from the plantaris, most treated groups exposed to POPs for 3 days are well distinguished from the control groups. However, for host mice exposed to POPs for 21 days, apart from the kidney and heart, groups are not well-distinguished from the control group. This study helps bring new insight into the effects of the pollutants mixture released from AT on fatty acid and lipid metabolism at different periods and how the dysregulation of metabolites might result in diseases associated with the organs.

Effect of Aerobic Exercise at Different Intensities on Intraocular Pressure in Young Males.

PRCIS: High intensity aerobic exercise significantly reduced intraocular pressure in healthy young male adults. OBJECTIVE: This study sought to determine how aerobic exercise at various intensities affects intraocular pressure (IOP) in young adults. DESIGN: A repeated measures design was adopted. PARTICIPANTS: A group of 20 volunteers (mean age: 21.24±1.73 y) took part in this study. METHODS: IOP was measured with a tonometer (iCare TA01i, Icare Finland, Finland). Subjects completed 4 cycle ergometer sessions. During the first session, power was increased by 60 W every 3 minutes until exhaustion, corresponding to peak power. For the 3 following tests, each lasting 25 minutes, subjects exercised at intensities of 50%, 70%, and 85% of peak power, respectively, and measurements were taken every 5 minutes. MAIN OUTCOME MEASURES: IOP, as determined using a tonometer, was the primary measure. RESULTS: There was a significant reduction ( P <0.05) in IOP of both eyes during the 25 minutes high-intensity (85%) exercise test. There were also significant interactions between exercise durations and intensities. During high-intensity exercise, IOP, blood pressure, blood lactate, and the rating of perceived exertion were significantly related ( P <0.01). CONCLUSIONS: These data show a significant reduction in IOP at high-intensity aerobic exercise, which may have implications for the management of ocular health.

COVID-19 and aerobic exercise: possible role of angiotensin converting enzyme 2.

The emergence and circulation of a novel coronavirus (2019-nCoV)-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-set off a global health crisis. SARS-CoV-2 spreads faster than its two ancestors, SARS-CoV and MERS-CoV. Several modes of transmission have been identified: via respiratory droplets, contact with infected people or contaminated surfaces, and potentially, bioaerosols. Various countries have taken preventive measures that may include partial or total lockdowns lasting weeks. The physical inactivity associated with lockdowns may promote cardiometabolic or other diseases, while physical activity may play a critical role in preventing them. Here we develop the hypothesis of the involvement of aerosols in the contamination process, the role of angiotensin converting enzyme 2 (ACE2), the potential benefits and harm of physical activity during lockdowns, and we suggest directions for future research.

Lack of Skeletal Muscle Serotonin Impairs Physical Performance.

Low levels of the neurotransmitter serotonin have been associated with the onset of depression. While traditional treatments include antidepressants, physical exercise has emerged as an alternative for patients with depressive disorders. Yet there remains the fundamental question of how exercise is sensed by the brain. The existence of a muscle-brain endocrine loop has been proposed: according to this scenario, exercise modulates metabolization of tryptophan into kynurenine within skeletal muscle, which in turn affects the brain, enhancing resistance to depression. But the breakdown of tryptophan into kynurenine during exercise may also alter serotonin synthesis and help limit depression. In this study, we investigated whether peripheral serotonin might play a role in muscle-brain communication permitting adaptation for endurance training. We first quantified tryptophan metabolites in the blood of 4 trained athletes before and after a long-distance trail race and correlated changes in tryptophan metabolism with physical performance. In parallel, to assess exercise capacity and endurance in trained control and peripheral serotonin-deficient mice, we used a treadmill incremental test. Peripheral serotonin-deficient mice exhibited a significant drop in physical performance despite endurance training. Brain levels of tryptophan metabolites were similar in wild-type and peripheral serotonin-deficient animals, and no products of muscle-induced tryptophan metabolism were found in the plasma or brains of peripheral serotonin-deficient mice. But mass spectrometric analyses revealed a significant decrease in levels of 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in both the soleus and plantaris muscles, demonstrating that metabolization of tryptophan into serotonin in muscles is essential for adaptation to endurance training. In light of these findings, the breakdown of tryptophan into peripheral but not brain serotonin appears to be the rate-limiting step for muscle adaptation to endurance training. The data suggest that there is a peripheral mechanism responsible for the positive effects of exercise, and that muscles are secretory organs with autocrine-paracrine roles in which serotonin has a local effect.

Srf KO and wild-type mice similarly adapt to endurance exercise.

Physical exercise has important effects as secondary prevention or intervention against several diseases. Endurance exercise induces local and global effects, resulting in skeletal muscle adaptations to aerobic activity and contributes to an amelioration of muscle performance. Furthermore, it prevents muscle loss. Serum response factor (Srf) is a transcription factor of pivotal importance for muscle tissues and animal models of Srf genetic deletion/over-expression are widely used to study Srf role in muscle homeostasis, physiology and pathology. A global characterisation of exercise adaptation in the absence of Srf has not been reported. We measured body composition, muscle force, running speed, energy expenditure and metabolism in WT and inducible skeletal muscle-specific Srf KO mice, following three weeks of voluntary exercise by wheel running. We found a major improvement in the aerobic capacity and muscle function in WT mice following exercise, as expected, and no major differences were observed in Srf KO mice as compared to WT mice, following exercise. Taken together, these observations suggest that Srf is not required for an early (within 3 weeks) adaptation to spontaneous exercise and that Srf KO mice behave similarly to the WT in terms of spontaneous physical activity and the resulting adaptive responses. Therefore, Srf KO mice can be used in functional muscle studies, without the results being affected by the lack of Srf. Since lack of Srf induces premature sarcopenia, our observations suggest that the modifications due to the absence of Srf take time to occur and that young, Srf KO mice behave similarly to WT in aerobic physical activities.

Metabolic syndrome, leptin-insulin resistance and uric acid: a trinomial foe for Algerian city-dweller adolescents' health.

Background Adolescence is one of the critical periods where increased risk for long-term obesity-related complications is an important health concern. This highlights the need to perform early diagnostics based on precise biomarkers to decrease the risk of complications in adolescents with obesity. Objective To determine the relationships between serum levels of uric acid (UA), leptin and insulin with metabolic syndrome (MS) components in Algerian adolescents. Subjects Nondiabetic adolescents (n = 204). Methods Blood pressure (BP) and anthropometric measurements were performed using standardized techniques. Blood samples were taken for determination of glycemia, triglyceridemia, uricemia, cholesterolemia, leptinemia and insulinemia. Results The rate of MS among an excess weight group was 17.4% [95% confidence interval (CI)]. Serum levels of UA, leptin and insulin were significantly higher in the excess weight group compared to a normal weight group (279.4 ± 86.05 vs. 204.9 ± 50.34 µmol/L and 25.65 ± 14.01 vs. 4.09 ± 2.60 µg/L, p < 0.001; 24.58 ± 13.85 vs. 13.34 ± 6.41 µIU/L, p < 0.05). Serum levels of UA, leptin and insulin were significantly higher in adolescents with MS compared to those without MS (304.86 ± 111.41 vs. 224.72 ± 77.81 µmol/L, 30.26 ± 12.46 vs. 16.93 ± 14.97 µg/L and 30.91 ± 17.30 vs. 18.71 ± 10.14 µIU/L, p < 0.05, respectively). Significant correlations were found between UA and leptin with waist circumference (r = 0.50 and 0.76), diastolic blood pressure (r = 0.58 and 0.43), triglycerides (r = 0.42 and 0.35) and high-density lipoprotein-cholesterol (r = -0.36 and -0.35). Conclusion Serum levels of UA and leptin may be useful biomarkers for early diagnosis of the risk of MS in our Algerian adolescent population.

A Mouse Model of Cardiomyopathy Induced by Mutations in the Hemochromatosis HFE Gene.

BACKGROUND: The heart is 1 of the organs most affected by hereditary hemochromatosis (HH). The clinical impact of cardiomyopathy in patients with HH requires a particular diagnosis and less invasive treatments. We developed a model of cardiomyopathy in knockout (KO) mice for the high-Fe (HFE) gene and assessed left ventricular (LV) function and structure from 7-20 months. METHODS: Male wild-type (WT) heterozygous and KO SV129 mice for the HFE gene were used in this study. Twenty-four mice were used to assess LV function and structure by echocardiography at 7, 14, 18, and 20 months. Evaluations of LV function and structure and myocardial fibrosis were performed at 7 and 20 months. RESULTS: The percent decrease of LV thickness-to-radius ratio between 7 and 20 months was higher in KO mice compared with WT mice (-30.2% ± 5.3% vs -10.5% ± 4.9%; P < 0.01). The LV diameters were higher in old mice compared with young mice (+13% at end-diastole; +33% at end-systole; P < 0.001). The LV ejection fraction values were lower in KO mice compared with WT mice between 7 and 20 months. The highest difference was found at 14 months (60.0% ± 7.6% vs 78.1% ± 3.5%; P < 0.001). Myocardial fibrosis was higher in old KO mice compared with old WT mice (+55%; P < 0.001), and myocardial iron deposition was slightly increased in old KO mice compared with old WT mice (1.31% ± 0.33% vs 0.84% ± 0.22%; P = 0.056). CONCLUSIONS: The present mouse model has the potential to allow the determination of underlying mechanisms involved in the cardiomyopathy induced by HFE-related hemochromatosis.

Relationships between metabolic profile, hypertension and uric acid with cardiometabolic risk in adolescents with abdominal obesity: impact of geodemographic factors on the prevalence of abdominal obesity.

Background Association of hyperuricemia, dyslipidemia and high blood pressure (BP) among adolescents with high waist-to-height ratio (WHtR) remains not fully addressed and could represent a new way to diagnose adolescents early with cardiometabolic risk. Objective We aimed to determine abdominal obesity (AO) prevalence and investigate relations between AO, uric acid (UA), lipid profiles, BP and geographical patterns in adolescents. Subjects 577 and 204 Algerian students aged between 10 and 19 years were included in our epidemiological and biochemical studies, respectively. Methods Height, weight, waist circumference (Wc) and hip circumferences, body mass index (BMI) and BP were measured. Fasting blood sampling was performed to measure glycemia, lipid profile, uricemia, insulinemia and leptinemia. The WHtR ≥0.50 was applied for the diagnosis of AO and geodemographics was evaluated. Results The prevalence of AO was 12.13% among all students, 19.17% and 16.39% among students living in urban and plain areas, respectively. The risk of AO may be reduced in rural and mountainous areas. Lipid parameters, UA, insulin and leptin serum concentrations were significantly increased in adolescents with WHtR ≥0.50 compared to those with WHtR <0.50. Cardiometabolic risk was increased with WHtR ≥0.50 and BMI >26. Means of BMI, Wc, BP, and lipid parameters were significantly increased in the fourth quartiles compared to the first quartile of UA. Conclusion Urban areas and plains represent factors contributing to AO and WHtR ≥0.50 may be used as a cut-off point to define risks of high BP, lipid abnormalities and UA serum level in Algerian adolescents.