scholarly journals A Peripheral CB1R Antagonist Increases Lipolysis, Oxygen Consumption Rate, and Markers of Beiging in 3T3-L1 Adipocytes Similar to RIM, Suggesting that Central Effects Can Be Avoided

2020 ◽  
Vol 21 (18) ◽  
pp. 6639
Author(s):  
Rebecca L. Paszkiewicz ◽  
Richard N. Bergman ◽  
Roberta S. Santos ◽  
Aaron P. Frank ◽  
Orison O. Woolcott ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Cannabinoid Receptor ◽  
In Vitro Assays ◽  
Mitochondrial Uncoupling ◽  
Direct Role ◽  
The Impact

With the increased prevalence of obesity and related co-morbidities, such as type 2 diabetes (T2D), worldwide, improvements in pharmacological treatments are necessary. The brain- and peripheral-cannabinoid receptor 1 (CB1R) antagonist rimonabant (RIM) has been shown to induce weight loss and improve glucose homeostasis. We have previously demonstrated that RIM promotes adipose tissue beiging and decreased adipocyte cell size, even during maintenance on a high-fat diet. Given the adverse side-effects of brain-penetrance with RIM, in this study we aimed to determine the site of action for a non-brain-penetrating CB1R antagonist AM6545. By using in vitro assays, we demonstrated the direct effects of this non-brain-penetrating CB1R antagonist on cultured adipocytes. Specifically, we showed, for the first time, that AM6545 significantly increases markers of adipose tissue beiging, mitochondrial biogenesis, and lipolysis in 3T3-L1 adipocytes. In addition, the oxygen consumption rate (OCR), consisting of baseline respiratory rate, proton leak, maximal respiratory capacity, and ATP synthase activity, was greater for cells exposed to AM6545, demonstrating greater mitochondrial uncoupling. Using a lipolysis inhibitor during real-time OCR measurements, we determined that the impact of CB1R antagonism on adipocytes is driven by increased lipolysis. Thus, our data suggest the direct role of CB1R antagonism on adipocytes does not require brain penetrance, supporting the importance of focus on peripheral CB1R antagonism pharmacology for reducing the incidence of obesity and T2D.

scholarly journals A Multiparametric Assessment of Human Islets Predicts Transplant Outcomes in Diabetic Mice

2021 ◽  
Vol 30 ◽  
pp. 096368972110522
Author(s):  
Hirotake Komatsu ◽  
Meirigeng Qi ◽  
Nelson Gonzalez ◽  
Mayra Salgado ◽  
Leonard Medrano ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Single Cells ◽  
Human Islets ◽  
In Vitro Assays ◽  
Diabetic Mice ◽  
Post Transplantation

Prior to transplantation into individuals with type 1 diabetes, in vitro assays are used to evaluate the quality, function and survival of isolated human islets. In addition to the assessments of these parameters in islet, they can be evaluated by multiparametric morphological scoring (0–10 points) and grading (A, B, C, D, and F) based on islet characteristics (shape, border, integrity, single cells, and diameter). However, correlation between the multiparametric assessment and transplantation outcome has not been fully elucidated. In this study, 55 human islet isolations were scored using this multiparametric assessment. The results were correlated with outcomes after transplantation into immunodeficient diabetic mice. In addition, the multiparametric assessment was compared with oxygen consumption rate of isolated islets as a potential prediction factor for successful transplantations. All islet batches were assessed and found to score: 9 points ( n = 18, Grade A), 8 points ( n = 19, Grade B), and 7 points ( n = 18, Grade B). Islets that scored 9 (Grade A), scored 8 (Grade B) and scored 7 (Grade B) were transplanted into NOD/SCID mice and reversed diabetes in 81.2%, 59.4%, and 33.3% of animals, respectively ( P < 0.0001). Islet scoring and grading correlated well with glycemic control post-transplantation ( P < 0.0001) and reversal rate of diabetes ( P < 0.05). Notably, islet scoring and grading showed stronger correlation with transplantation outcome compared to oxygen consumption rate. Taken together, a multiparametric assessment of isolated human islets was highly predictive of transplantation outcome in diabetic mice.

scholarly journals Myricetin Exerts Anti-Obesity Effects through Upregulation of SIRT3 in Adipose Tissue

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1962 ◽  
Author(s):  
Seun Akindehin ◽  
Young-Suk Jung ◽  
Sang-Nam Kim ◽  
Yeon-Ho Son ◽  
Icksoo Lee ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Biologically Active ◽  
Beneficial Effects ◽  
Reduced Body ◽  
Sirt3 Expression

Myricetin is a biologically active natural polyphenol with beneficial effects on metabolic health. This study aimed to examine the effects of myricetin on the expression levels of genes involved in lipolysis and mitochondrial respiration in adipocytes and the anti-obesity potential of myricetin. The results indicated that myricetin reduced triglyceride (TG) content and increased mitochondrial content and oxygen consumption rate (OCR) in adipocytes in vitro. To determine anti-obesity effect of myricetin, C57BL6/J mice were fed a high-fat diet (HFD) for eight weeks and then treated with myricetin (10 mg/kg) for 2 weeks. The in vivo treatment of myricetin reduced body weight by 11%. Furthermore, it improved the glucose tolerance, and increased fatty acid consumption of HFD-fed mice. Myricetin treatment increased Sirt3 expression and reduced the acetylation of mitochondrial proteins in adipose tissue. Finally, the knockdown of Sirt3 in adipocytes reduced the myricetin-induced increase in mitochondrial oxygen consumption rate by about 27% compared to controls. Our results indicated that myricetin exerted anti-obesity effects through the upregulation of Sirt3 expression and mitochondrial metabolism in adipose tissue.

scholarly journals Necrostatin-1 Supplementation to Islet Tissue Culture Enhances the In-Vitro Development and Graft Function of Young Porcine Islets

2021 ◽  
Vol 22 (16) ◽  
pp. 8367
Author(s):  
Hien Lau ◽  
Shiri Li ◽  
Nicole Corrales ◽  
Samuel Rodriguez ◽  
Mohammadreza Mohammadi ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Oxygen Consumption ◽  
Insulin Secretion ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
In Vitro Development ◽  
Porcine Islets ◽  
Vitro Development

Pre-weaned porcine islets (PPIs) represent an unlimited source for islet transplantation but are functionally immature. We previously showed that necrostatin-1 (Nec-1) immediately after islet isolation enhanced the in vitro development of PPIs. Here, we examined the impact of Nec-1 on the in vivo function of PPIs after transplantation in diabetic mice. PPIs were isolated from pancreata of 8–15-day-old, pre-weaned pigs and cultured in media alone, or supplemented with Nec-1 (100 µM) on day 0 or on day 3 of culture (n = 5 for each group). On day 7, islet recovery, viability, oxygen consumption rate, insulin content, cellular composition, insulin secretion capacity, and transplant outcomes were evaluated. While islet viability and oxygen consumption rate remained high throughout 7-day tissue culture, Nec-1 supplementation on day 3 significantly improved islet recovery, insulin content, endocrine composition, GLUT2 expression, differentiation potential, proliferation capacity of endocrine cells, and insulin secretion. Adding Nec-1 on day 3 of tissue culture enhanced the islet recovery, proportion of delta cells, beta-cell differentiation and proliferation, and stimulation index. In vivo, this leads to shorter times to normoglycemia, better glycemic control, and higher circulating insulin. Our findings identify the novel time-dependent effects of Nec-1 supplementation on porcine islet quantity and quality prior to transplantation.

THE IN VITRO ACTION OF ACTH ON THE OXYGEN CONSUMPTION OF SLICES OF CATTLE ADRENAL CORTEX

1953 ◽  
Vol 9 (4) ◽  
pp. 379-390 ◽  
Author(s):  
M. REISS ◽  
EVA BRUMMEL ◽  
I. D. K. HALKERSTON ◽  
F. E. BADRICK ◽  
M. FENWICK
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Uptake ◽  
Linear Relationship ◽  
Adrenal Cortex ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Biological Assay ◽  
Percentage Increase ◽  
Small Doses

A technique for measuring the action of small doses of ACTH on the oxygen consumption of slices of cattle adrenal cortex is described. The oxygen consumption rate of such slices in vitro is increased by ACTH. A linear relationship between logarithm of the dose of ACTH and the percentage increase in the rate of oxygen uptake is obtained with this method, and its suitability for biological assay purposes has been investigated. The question of the specificity of this action of ACTH is discussed.

Development of a new oxygen consumption rate assay in cultures of Acanthamoeba (Protozoa: Lobosea) and its application to evaluate viability and amoebicidal activity in vitro

2015 ◽  
Vol 155 ◽  
pp. 35-39 ◽  
Author(s):  
I. Heredero-Bermejo ◽  
A. Criado-Fornelio ◽  
J. Soliveri ◽  
J.A. Díaz-Martín ◽  
J. Matilla-Fuentes ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Amoebicidal Activity

scholarly journals The impact of high and low atmospheric pressure in the Jordanian environment on some physiological variable for runners .

2013 ◽  
Vol 4 (2) ◽  
pp. 364
Author(s):  
Baker Thnibat
Keyword(s):  
Oxygen Consumption ◽  
Energy Expenditure ◽  
Atmospheric Pressure ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Maximal Oxygen Consumption ◽  
Training Groups ◽  
Low Atmospheric Pressure ◽  
The Impact ◽  
High Atmospheric Pressure

<p>The study aimed at identifying the impact of difference between the areas of high atmospheric pressure in the Jordanian environment on some physiological variable ( estimating maximal oxygen consumption , estimating rate of Energy expenditure, and hemoglobin ,vital capacity), for runners .</p><p>  The study sample consisted of (16) athletes who practice ( middle and long – distance running). A number of statistical methods were used to answer the questions of the study ( arithmetic means , standard deviations , Mann.Whiteny test ,and the result of Kolmogorov – Smirnov tests ) .</p><p>  The study result concluded that there was apriority for the measurements which were conducted on the training groups of low atmospheric pressure in comparison with the other group, with regard to the  variables (maximal oxygen consumption , rate of Energy expenditure, and hemoglobin). The study result also showed that there was apriority for the measurements which were conducted on the training groups of high  atmospheric pressure in comparison with the other group, regarding  to the  variables (maximal oxygen consumption , rate of Energy expenditure, and hemoglobin).in the areas of high  atmospheric pressure.</p><p>The study result also suggested that ther were no statistically significant differences between two training groups with regard to the study variables of (maximal oxygen consumption , rate of Energy expenditure, and hemoglobin ,vital capacity), were measured in  of high atmospheric pressure areas .</p><p>The study recommended about building sports facilities that simulate the areas of low atmospheric pressure , because of the expected role that the factors would play in improving some physiological variables .</p>

scholarly journals Event-Associated Oxygen Consumption Rate Increases ca. Five-Fold When Interictal Activity Transforms into Seizure-Like Events In Vitro

2017 ◽  
Vol 18 (9) ◽  
pp. 1925 ◽  
Author(s):  
Karl Schoknecht ◽  
Nikolaus Berndt ◽  
Jörg Rösner ◽  
Uwe Heinemann ◽  
Jens Dreier ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Consumption Rate ◽  
Consumption Rate

Oxygen consumption by bovine granulosa cells with prediction of oxygen transport in preantral follicles

2013 ◽  
Vol 25 (8) ◽  
pp. 1158 ◽  
Author(s):  
Dongxing Li ◽  
Gabe P. Redding ◽  
John E. Bronlund
Keyword(s):  
Oxygen Consumption ◽  
Granulosa Cells ◽  
Oxygen Transport ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Model Parameters ◽  
Preantral Follicles ◽  
Rate Of Oxygen Consumption ◽  
Key Parameter

The rate of oxygen consumption by granulosa cells is a key parameter in mathematical models that describe oxygen transport across ovarian follicles. This work measured the oxygen consumption rate of bovine granulosa cells in vitro to be in the range 2.1–3.3 × 10–16 mol cell–1 s–1 (0.16–0.25 mol m–3 s–1). The implications of the rates for oxygen transport in large bovine preantral follicles were examined using a mathematical model. The results indicate that oocyte oxygenation becomes increasingly constrained as preantral follicles grow, reaching hypoxic levels near the point of antrum formation. Beyond a preantral follicle radius of 134 µm, oxygen cannot reach the oocyte surface at typical values of model parameters. Since reported sizes of large bovine preantral follicles range from 58 to 145 µm in radius, this suggests that oocyte oxygenation is possible in all but the largest preantral follicles, which are on the verge of antrum formation. In preantral bovine follicles, the oxygen consumption rate of granulosa cells and fluid voidage will be the key determinants of oxygen levels across the follicle.

scholarly journals Exosomal microRNA-503-3p derived from macrophages represses glycolysis and promotes mitochondrial oxidative phosphorylation in breast cancer cells by elevating DACT2

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shulin Huang ◽  
Peizhi Fan ◽  
Chaojie Zhang ◽  
Jing Xie ◽  
Xiaowen Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Signaling Pathway ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Atp Level ◽  
Glucose Intake ◽  
The Impact

AbstractMicroRNAs (miRNAs) are emerging drivers in tumor progression, while the role of miR-503-3p in breast cancer (BC) remains largely unknown. We aimed to explore the impact of macrophage-derived exosomal miR-503-3p in the development of BC by regulating disheveled-associated binding antagonist of beta-catenin 2 (DACT2). miR-503-3p and DACT2 expression in BC tissues and cells was assessed, and the expression of Wnt/β-catenin signaling pathway-related proteins in BC cells was also evaluated. Macrophages were induced and exosomes were extracted. The screened BC cell lines were, respectively, treated with exosomes, miR-503-3p inhibitor/mimic or upregulated/inhibited DACT2, and then the phenotypes, glucose intake, oxygen consumption rate, and adenosine-triphosphate (ATP) level of BC cells were determined. Cell growth in vivo was also observed. MiR-503-3p was elevated, DACT2 was reduced, and Wnt/β-catenin signaling pathway was activated in BC cells. Macrophage-derived exosomes, upregulated miR-503-3p or inhibited DACT2 promoted malignant behaviors of BC cells, glucose intake, and activity of the Wnt/β-catenin signaling pathway, while repressed oxygen consumption rate and ATP level in BC cells. Reversely, reduced miR-503-3p or upregulated DACT2 exerted opposite effects. This study revealed that reduction of macrophage-derived exosomal miR-503-3p repressed glycolysis and promoted mitochondrial oxidative phosphorylation in BC by elevating DACT2 and inactivating Wnt/β-catenin signaling pathway. Our research may provide novel targets for BC treatment.

scholarly journals Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Mengling Wang ◽  
Feng Zeng ◽  
Fengling Ning ◽  
Yinhang Wang ◽  
Shilin Zhou ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Consumption Rate ◽  
Renal Fibrosis ◽  
Consumption Rate ◽  
Metabolic Reprogramming ◽  
Ceria Nanoparticles ◽  
Extracellular Acidification ◽  
Extracellular Acidification Rate

Abstract Background and aims Renal fibrosis is the common outcome in all progressive forms of chronic kidney disease. Unfortunately, the pathogenesis of renal fibrosis remains largely unexplored, among which metabolic reprogramming plays an extremely crucial role in the evolution of renal fibrosis. Ceria nanoparticles (CeNP-PEG) with strong ROS scavenging and anti-inflammatory activities have been applied for mitochondrial oxidative stress and inflammatory diseases. The present study aims to determine whether CeNP-PEG has therapeutic value for renal fibrosis. Methods The unilateral ureteral obstructive fibrosis model was used to assess the therapeutic effects in vivo. Transforming growth factor beta1-induced epithelial-to-mesenchymal transition in HK-2 cells was used as the in vitro cell model. The seahorse bioscience X96 extracellular flux analyzer was used to measure the oxygen consumption rate and extracellular acidification rate. Results In the present study, CeNP-PEG treatment significantly ameliorated renal fibrosis by increased E-cadherin protein expression, and decreased α-SMA, Vimentin and Fibronectin expression both in vitro and in vivo. Additionally, CeNP-PEG significantly reduced the ROS formation and improved the levels of mitochondrial ATP. The seahorse analyzer assay demonstrated that the extracellular acidification rate markedly decreased, whereas the oxygen consumption rate markedly increased, in the presence of CeNP-PEG. Furthermore, the mitochondrial membrane potential markedly enhanced, hexokinase 1 and hexokinase 2 expression significantly decreased after treatment with CeNP-PEG. Conclusions CeNP-PEG can block the dysregulated metabolic status and exert protective function on renal fibrosis. This may provide another therapeutic option for renal fibrosis. Graphical Abstract

Sign in / Sign up

Export Citation Format

Share Document