scholarly journals Metabolic Impairments Caused by Pesticides in Mammals and Their Interactions with Other Pollutants

2019 ◽  
Author(s):  
Gema Rodríguez-Moro ◽  
Ana Arias-Borrego ◽  
Sara Ramírez-Acosta ◽  
Francisco Navarro-Roldán ◽  
Nieves Abril-Díaz ◽  
...  
Keyword(s):  
Metabolic Impairments

scholarly journals Bioenergetic and metabolic impairments in Duchenne Muscular Dystrophy (DMD) patients' iPSC-derived cardiomyocytes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Willi ◽  
B Agranovich ◽  
I Abramovich ◽  
D Freimark ◽  
M Arad ◽  
...  
Keyword(s):  
Stress Test ◽  
Young Male ◽  
Induced Pluripotent Stem Cell ◽  
Dystrophin Gene ◽  
Energy System ◽  
Basal Respiration ◽  
Mitochondrial Activity ◽  
Funding Source ◽  
Atp Production ◽  
Metabolic Impairments

Abstract Introduction DMD, an X-linked muscle degenerative fatal disease, is caused by mutations in the dystrophin gene. Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality in DMD patients. Treatments for DCM in DMD are limited to steroids and standard heart failure medications such as β-blockers and ACE-inhibitors, and therefore novel therapeutic modalities are urgently needed. Purpose We hypothesized that dystrophin mutations in DMD lead to cardiomyopathy-causing bioenergetic/metabolic impairments, which can be therapeutically targeted for improving cardiac function. Methods Induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs) were generated from healthy volunteer and 3 DMD patients: young male (YM), adult male (AM) and adult female (AF). We investigated the bioenergetics, electrophysiology, mitochondrial and metabolic features of healthy and DMD iPSC-CMs using the Seahorse Flux analyzer, patch clamp, confocal fluorescence microscopy and Liquid chromatography mass spectrometry (LC-MS) technologies, respectively. Results To test the hypothesis, we measured respiration and glycolytic rates of healthy and DMD iPSC-CMs. Compared to healthy iPSC-CMs, in both AM and AF DMD, but not in YM DMD cardiomyocytes, there was a 75% decrease in ATP production, and 80% and 45% decrease in basal respiration, respectively. In agreement with the healthy-like bioenergetic status of YM, the iPSC-CMs showed no arrhythmias, in contrast to the prominent arrhythmias in AM and AF cardiomyocytes. To determine whether the impairment in the phosphorylation pathway (OXPHOS) affects glycolysis, we measured the cardiomyocytes' response to glycolytic stress test. These experiments showed that the glycolytic rates were similar in healthy and DMD iPSC-CMs. In agreement with impaired OXPHOS, mitochondrial activity measured by 3D life confocal microscopy was attenuated in the DMD male by 35%, compared to healthy cardiomyocytes. Furthermore, the metabolomic LC-MS analyses demonstrated significant differences in metabolite levels in YM, AM and AF DMD iPSC-CMs relative to healthy iPSC-CMs. For example, compared to healthy iPSC-CMs, there was a dramatic fall to undetected levels in phosphocreatine in both AM and AF, but not in YM DMD, indicating a dysfunctional phosphocreatine energy system. Conclusions DMD iPSC-CMs exhibit bioenergetic/metabolic impairments, which constitute novel targets for alleviating the cardiomyopathy in DMD patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): ISF - Israel Science Foundation

The development of diet-induced obesity and associated metabolic impairments in Dj-1 deficient mice

2015 ◽  
Vol 26 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Katrin Seyfarth ◽  
Gereon Poschmann ◽  
Jan Rozman ◽  
Tobias Fromme ◽  
Nadine Rink ◽  
...  
Keyword(s):  
Diet Induced Obesity ◽  
Deficient Mice ◽  
Metabolic Impairments

scholarly journals Repeated clodronate-liposome treatment results in neutrophilia and is not effective in limiting obesity-linked metabolic impairments

2019 ◽  
Vol 316 (3) ◽  
pp. E358-E372 ◽  
Author(s):  
Jackie E. Bader ◽  
Reilly T. Enos ◽  
Kandy T. Velázquez ◽  
Meredith S. Carson ◽  
Alex T. Sougiannis ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Intake ◽  
Complete Blood Count ◽  
Therapeutic Option ◽  
Intraperitoneal Administration ◽  
Direct Result ◽  
Metabolic Dysfunction ◽  
Macrophage Depletion ◽  
Clodronate Liposome ◽  
Metabolic Impairments

Depletion of macrophages is thought to be a therapeutic option for obesity-induced inflammation and metabolic dysfunction. However, whether the therapeutic effect is a direct result of reduced macrophage-derived inflammation or secondary to decreases in fat mass is controversial, as macrophage depletion has been shown to disrupt energy homeostasis. This study was designed to determine if macrophage depletion via clodronate-liposome (CLD) treatment could serve as an effective intervention to reduce obesity-driven inflammatory and metabolic impairments independent of changes in energy intake. After 16 wk on a high-fat diet (HFD) or the AIN-76A control (low-fat) diet (LFD) ( n = 30/diet treatment), male C57BL/6J mice were assigned to a CLD- or PBS-liposome treatment ( n = 15/group) for 4 wk. Liposomes were administered biweekly via intraperitoneal injections (8 administrations in total). PBS-liposome-treated groups were pair-fed to their CLD-treated dietary counterparts. Metabolic function was assessed before and after liposome treatment. Adipose tissue, as well as the liver, was investigated for macrophage infiltration and the presence of inflammatory mediators. Additionally, a complete blood count was performed. CLD treatment reduced energy intake. When controlling for energy intake, CLD treatment was unable to regress metabolic dysfunction or nonalcoholic fatty liver disease and impaired adipose tissue insulin action. Moreover, repeated CLD treatment induced neutrophilia and anemia, increased adipose tissue mRNA expression of the proinflammatory cytokines IL-6 and IL-1β, and augmented circulating IL-6 and monocyte chemoattractant protein-1 concentrations ( P < 0.05). This study suggests that repeated intraperitoneal administration of CLD to deplete macrophages attenuates obesity by limiting energy intake. Moreover, after controlling for the benefits of weight loss, the accompanying detrimental side effects limit regular CLD treatment as an effective therapeutic strategy.

scholarly journals Metabolic Therapy in Heart Failure

2015 ◽  
Vol 1 (2) ◽  
pp. 112 ◽  
Author(s):  
Yury Lopatin ◽  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Glucose Oxidation ◽  
Acid Oxidation ◽  
Patients With Heart Failure ◽  
Cardiac Energy Metabolism ◽  
Conventional Medical Therapy ◽  
Cardiac Energy ◽  
Metabolic Impairments

Metabolic impairments play an important role in the development and progression of heart failure. The use of metabolic modulators, the number of which is steadily increasing, may be particularly effective in the treatment of heart failure. Recent evidence suggests that modulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation represents a promising approach to the treatment of patients with heart failure. This review focuses on the role of metabolic modulators, in particular trimetazidine, as a potential additional medication to conventional medical therapy in heart failure.

scholarly journals Metabolomics profiling reveals profound metabolic impairments in mice and patients with Sandhoff disease

2019 ◽  
Vol 126 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Li Ou ◽  
Michael J. Przybilla ◽  
Chester B. Whitley
Keyword(s):  
Sandhoff Disease ◽  
Metabolic Impairments

Daytime Napping Duration Is Positively Associated With Risk of Hyperuricemia in a Chinese Population

2021 ◽  
Author(s):  
Yanjiao Wang ◽  
Yongli Zeng ◽  
Xuehui Zhang ◽  
Qiong Meng ◽  
Fei Mi ◽  
...  
Keyword(s):  
Sleep Duration ◽  
Chinese Population ◽  
Metabolic Risk ◽  
Sleep Habits ◽  
Nocturnal Sleep ◽  
Yunnan Region ◽  
Crude Model ◽  
Adjusted Model ◽  
Multivariable Adjustment ◽  
Metabolic Impairments

Abstract Context Loss of sleep or disturbance of sleep-wake cycles has been related to metabolic impairments. However, few studies have investigated the association between daily sleep duration and hyperuricemia. Objective We investigated daily sleep duration (daytime napping and nocturnal sleep) with hyperuricemia risk. Methods We cross-sectionally analyzed data from the China Multi-Ethnic Cohort (CMEC), Yunnan region. A total of 22 038 participants aged 30 to 79 years were recruited in 2018. Hyperuricemia was defined as serum uric acid (SUA) above 7.0 mg/dL in men and above 6.0 mg/dL in women. Outcomes were associations between daily sleep duration and hyperuricemia. Results We found that the longest daytime napping duration was associated with a higher risk of hyperuricemia in the crude model (odds ratio [OR] [95% CI], 2.22 [1.88-2.61], P &lt; .001) and in a multivariable adjustment model (OR, 1.69; 95% CI, 1.41-2.01, P &lt; .001) after adjusting for demographic, sleep habits, and metabolic risk factors. The association was moderately attenuated with additionally adjusted for serum creatinine (OR, 1.54; 95% CI, 1.28-1.86, P &lt; .001). Longer daytime napping duration was also related to higher risk of hyperuricemia combined with metabolic syndrome (MetS). Respondents in the group with daytime napping duration greater than or equal to 90 minutes presented with a higher risk of hyperuricemia combined with MetS (OR, 1.39; 95% CI, 1.06-1.79; P &lt; .001) in the fully adjusted model. We did not observe any relation between nocturnal sleep duration and risk of hyperuricemia in the study. Conclusion Longer daytime napping duration (but not nocturnal sleep duration) was independently associated with risk of hyperuricemia in a Chinese population.

Use of Succinates for Correction of Metabolic Impairments in the Ischemic Penumbra Zone in Stroke Patients

2015 ◽  
Vol 45 (5) ◽  
pp. 600-604
Author(s):  
M. M. Odinak ◽  
S. N. Yanishevskii ◽  
N. V. Tsygan ◽  
S. Yu. Golokhvastov ◽  
I. A. Voznyuk ◽  
...  
Keyword(s):  
Ischemic Penumbra ◽  
Stroke Patients ◽  
Metabolic Impairments
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