scholarly journals NFκB Regulates Muscle Development and Mitochondrial Function

2018 ◽  
Vol 75 (4) ◽  
pp. 647-653 ◽  
Author(s):  
Joseph M Valentine ◽  
Mengyao E Li ◽  
Steven E Shoelson ◽  
Ning Zhang ◽  
Robert L Reddick ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Life Span ◽  
Muscle Mass ◽  
Mitochondrial Function ◽  
Muscle Development ◽  
Tissue Mass ◽  
Lower Oxygen ◽  
Consumption Rates ◽  
Nfκb Pathway ◽  
Gastrocnemius Muscles

Abstract Nuclear factor (NF)κB is a transcription factor that controls immune and inflammatory signaling pathways. In skeletal muscle, NFκB has been implicated in the regulation of metabolic processes and tissue mass, yet its affects on mitochondrial function in this tissue are unclear. To investigate the role of NFκB on mitochondrial function and its relationship with muscle mass across the life span, we study a mouse model with muscle-specific NFκB suppression (muscle-specific IκBα super-repressor [MISR] mice). In wild-type mice, there was a natural decline in muscle mass with aging that was accompanied by decreased mitochondrial function and mRNA expression of electron transport chain subunits. NFκB inactivation downregulated expression of PPARGC1A, and upregulated TFEB and PPARGC1B. NFκB inactivation also decreased gastrocnemius (but not soleus) muscle mass in early life (1–6 months old). Lower oxygen consumption rates occurred in gastrocnemius and soleus muscles from young MISR mice, whereas soleus (but not gastrocnemius) muscles from old MISR mice displayed increased oxygen consumption compared to age-matched controls. We conclude that the NFκB pathway plays an important role in muscle development and growth. The extent to which NFκB suppression alters mitochondrial function is age dependent and muscle specific. Finally, mitochondrial function and muscle mass are tightly associated in both genotypes and across the life span.

scholarly journals A Multivariate Metabolomics Method for Estimating Platelet Mitochondrial Oxygen Consumption Rates in Patients with Sepsis

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 139
Author(s):  
Marc R. McCann ◽  
Cora E. McHugh ◽  
Maggie Kirby ◽  
Theodore S. Jennaro ◽  
Alan E. Jones ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Mitochondrial Function ◽  
Regression Models ◽  
Consumption Rate ◽  
P Value ◽  
Linear Regression Models ◽  
Mitochondrial Oxygen Consumption ◽  
Non Invasive ◽  
Consumption Rates ◽  
Multiple Linear Regression Models

Background: Sepsis-induced alterations in mitochondrial function contribute to organ dysfunction and mortality. Measuring mitochondrial function in vital organs is neither feasible nor practical, highlighting the need for non-invasive approaches. Mitochondrial function may be reflected in the concentrations of metabolites found in platelets and whole blood (WB) samples. We proposed to use these as alternates to indirectly estimate platelet mitochondrial oxygen consumption rate (mOCR) in sepsis patients. Methods: We determined the relationships between platelet mOCR and metabolites in both platelets and WB, as measured by quantitative 1H-NMR metabolomics. The associations were identified by building multiple linear regression models with stepwise forward-backward variable selection. We considered the models to be significant with an ANOVA test (p-value ≤ 0.05) and a positive predicted-R2. Results: The differences in adjusted-R2 and ANOVA p-values (platelet adj-R2: 0.836 (0.0003), 0.711 (0.0004) vs. WB adj-R2: 0.428 (0.0079)) from the significant models indicate the platelet models were more associated with platelet mOCR. Conclusions: Our data suggest there are groups of metabolites in WB (leucine, acetylcarnitine) and platelets (creatine, ADP, glucose, taurine) that are associated with platelet mOCR. Thus, WB and platelet metabolites could be used to estimate platelet mOCR.

87 EVALUATION OF MITOCHONDRIAL FUNCTION IN SINGLE CLONED MINIATURE PIG EMBRYOS BY MEASURING OXYGEN CONSUMPTION

2007 ◽  
Vol 19 (1) ◽  
pp. 161
Author(s):  
S. Sugimura ◽  
M. Yokoo ◽  
K.-I. Yamanaka ◽  
T. Wakai ◽  
H. Abe ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Mitochondrial Function ◽  
Blastocyst Stage ◽  
Miniature Pig ◽  
Cell Stage ◽  
Significant Difference ◽  
Lower Oxygen ◽  
Energy Synthesis ◽  
Mitochondrial Uncoupler

Mitochondria are organelles that produce energy for embryogensis. Their function [oxidative phosphorylation (OXPHOS) and electron transport] is regulated by intercommunication with the nucleus. In somatic cell nuclear transfer (SCNT) embryos, incomplete reprogramming may lead to dysfunction of the intercommunication before or after embryonic activation, or both, although it is unknown whether reprogramming for energy synthesis is required. In the previous report (Abe et al. 2004 J. Mamm. Ova Rec. 21, 22), we developed a noninvasive method using a scanning electrochemical microscopy (SECM) for measurement of oxygen consumption that provides more direct information about mitochondrial function (Trimarch et al. 2000 Biol. Reprod. 62, 1866–1874). In the present study to evaluate mitochondrial function in individual miniature pig SCNT embryos, we measured oxygen consumption by SECM. Oocytes in pig ovaries collected from the local slaughterhouse were matured for 44 h in NCSU23 and used as recipient. After SCNT with fetal miniature pig fibroblasts, reconstructed embryos were cultured in vitro in NCSU23 or PZM-3. Oxygen consumption in single 2- and 4-cell-stage embryos, morulae, and blastocysts were measured, and the values were compared with those derived from IVF. All data were analyzed by ANOVA. In IVF embryos, oxygen consumption was lowest at the 2- and 4-cell stages, and reached a peak at the blastocyst stage on Day 5. However, there were significant differences (P < 0.05) in blastocysts between NCSU23 and PZM-3: 0.61 � 0.14 vs. 0.83 � 0.18 at Day 5, 0.53 � 0.14 vs. 0.70 � 0.24 at Day 6, 0.47 � 0.11 vs. 0.73 � 0.20 � 10-14 mol s-1 at Day 7, respectively. In contrast, SCNT embryos showed no increase in oxygen consumption during pre-implantation stages in the 2 media, but there was a significant difference (P < 0.05) at the 2-cell stage between NCSU23 and PZM-3 (0.35 � 0.09 vs. 0.43 � 0.10, respectively). Comparison of the Day 5 IVF and SCNT blastocysts cultured in PZM-3 showed no difference in total cell numbers but significantly (P < 0.05) lower oxygen consumption in SCNT (0.83 � 0.18 vs. 0.40 � 0.13 � 10-14 mol s-1, respectively). After treatment with 1 �M CCCP (mitochondrial uncoupler) or 1 mM NaCN (mitochondrial electron transporter inhibitor), oxygen consumption in IVF and SCNT blastocysts at Day 5 increased (112 � 18 and 51 � 44%, respectively) or decreased (50 � 20 and 21 � 32%, respectively) compared with those of nontreated embryos. Sensitivity to these reagents differed significantly (P < 0.05) between IVF and SCNT, indicating that the SCNT blastocysts had a lower OXPHOS capacity than those from IVF. These results suggest that reprogramming for sustaining mitochondrial function during pre-implantation development may be required in miniature pig SCNT embryos.

scholarly journals Measuring mitochondrial respiration in intact single muscle fibers

2012 ◽  
Vol 302 (6) ◽  
pp. R712-R719 ◽  
Author(s):  
Rosemary A. Schuh ◽  
Kathryn C. Jackson ◽  
Ramzi J. Khairallah ◽  
Christopher W. Ward ◽  
Espen E. Spangenburg
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Mitochondrial Function ◽  
Muscle Fibers ◽  
Peak Oxygen Consumption ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Total Oxygen ◽  
Novel Approach ◽  
Consumption Rates

Measurement of mitochondrial function in skeletal muscle is a vital tool for understanding regulation of cellular bioenergetics. Currently, a number of different experimental approaches are employed to quantify mitochondrial function, with each involving either mechanically or chemically induced disruption of cellular membranes. Here, we describe a novel approach that allows for the quantification of substrate-induced mitochondria-driven oxygen consumption in intact single skeletal muscle fibers isolated from adult mice. Specifically, we isolated intact muscle fibers from the flexor digitorum brevis muscle and placed the fibers in culture conditions overnight. We then quantified oxygen consumption rates using a highly sensitive microplate format. Peak oxygen consumption rates were significantly increased by 3.4-fold and 2.9-fold by simultaneous stimulation with the uncoupling agent, carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP), and/or pyruvate or palmitate exposure, respectively. However, when calculating the total oxygen consumed over the entire treatment, palmitate exposure resulted in significantly more oxygen consumption compared with pyruvate. Further, as proof of principle for the procedure, we isolated fibers from the mdx mouse model, which has known mitochondrial deficits. We found significant reductions in initial and peak oxygen consumption of 51% and 61% compared with fibers isolated from the wild-type (WT) animals, respectively. In addition, we determined that fibers isolated from mdx mice exhibited less total oxygen consumption in response to the FCCP + pyruvate stimulation compared with the WT mice. This novel approach allows the user to make mitochondria-specific measures in a nondisrupted muscle fiber that has been isolated from a whole muscle.

scholarly journals ASSESSMENT OF A MICROPLATE SYSTEM FOR MEASURING INDIVIDUAL REAL-TIME RESPIRATION IN SMALL MODEL ORGANISMS OF AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S918-S919
Author(s):  
Ashley N Turner ◽  
Jessica M Hoffman ◽  
Mickie L Powell ◽  
Melissa J Sammy ◽  
Douglas R Moellering ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Real Time ◽  
Mitochondrial Function ◽  
Genetic Model ◽  
Living Organism ◽  
Preliminary Evidence ◽  
Model Organisms ◽  
Zebrafish Embryos ◽  
Clinical Genetic ◽  
Consumption Rates

Abstract The ability to measure oxygen consumption rates of a living organism in real-time provides an indirect method of monitoring dynamic changes in metabolism reflecting organismal level mitochondrial function. In this study, we assessed the Loligo Systems microplate system for measuring individual respiration in small organisms. This included adult nematodes (Caenorhabditis elegans, N2), zebrafish embryos (Danio rerio, AB), and adult fruit flies (Drosophila melanogaster, w1118). Organisms were placed inside 80 µL glass chambers on a 24-well microplate atop a 24-channel optical fluorescence oxygen reading device. Adult nematodes and zebrafish embryos were in liquid culture, M9 buffer and egg water respectively, and the adult flies were in room air. The microplate and reader were placed inside an incubator for temperature control. A silicone gasket with a thin liner was used to seal the chambers. Reference standard oxygen consumption (respiration) of single and multiple adult nematodes (n=1–4 animals/well), zebrafish embryos (n=1–4 animals/well), and adult flies (n=1–2 animals/well) in the microplate system were achieved. Significant differences across numbers of animals/well and by sex were observed. Validation experiments of the oxygen consumption rates measured in C. elegans in parallel with Seahorse extracellular flux (XF) experiments are underway. The Loligo Systems microplate system offers a non-invasive, non-destructive method to measure real-time respiration in smaller organisms. These data provide preliminary evidence for utility of the system for a variety of biomedical applications that relate to organismal and mitochondrial function/dysfunction, including research in the basic biology of aging in these highly-utilized, pre-clinical, genetic model organisms.

Supplementation with beta-hydroxy-beta-methylbutyrate impacts glucose homeostasis and increases liver size in trained mice

2020 ◽  
Vol 90 (1-2) ◽  
pp. 113-123
Author(s):  
Ines Schadock ◽  
Barbara G. Freitas ◽  
Irae L. Moreira ◽  
Joao A. Rincon ◽  
Marcio Nunes Correa ◽  
...  
Keyword(s):  
Strength Training ◽  
Muscle Mass ◽  
Glucose Homeostasis ◽  
Fasting Blood Glucose ◽  
Hepatic Metabolism ◽  
Mass Gain ◽  
Trained Group ◽  
Tissue Mass ◽  
Liver Size ◽  
Intensive Training

Abstract. β-hydroxy-β-methyl butyrate (HMB) is a bioactive metabolite derived from the amino acid leucine, usually applied for muscle mass increase during physical training, as well as for muscle mass maintenance in debilitating chronic diseases. The hypothesis of the present study is that HMB is a safe supplement for muscle mass gain by strength training. Based on this, the objective was to measure changes in body composition, glucose homeostasis and hepatic metabolism of HMB supplemented mice during strength training. Two of four groups of male mice (n = 6/group) underwent an 8-week training period session (climbing stairs) with or without HMB supplementation (190 mg/kgBW per day). We observed lower body mass gain (4.9 ± 0.43% versus 1.2 ± 0.43, p < 0.001) and increased liver mass (40.9 ± 0.9 mg/gBW versus 44.8 ± 1.3, p < 0.001) in the supplemented trained group compared with the non-supplemented groups. The supplemented trained group had an increase in relative adipose tissue mass (12.4 ± 0.63 mg/gBW versus 16.1 ± 0.88, P < 0.01) compared to the non-supplemented untrained group, and an increase in fasting blood glucose (111 ± 4.58 mg/dL versus 122 ± 3.70, P < 0.05) and insulin resistance (3.79 ± 0.19 % glucose decay/min versus 2.45 ± 0.28, P < 0.05) comparing with non-supplemented trained group. Adaptive heart hypertrophy was observed only in the non-supplemented trained group (4.82 ± 0.05 mg/gBW versus 5.12 ± 0.13, P < 0.05). There was a higher hepatic insulin-like growth factor-1 expression (P = 0.002) in supplemented untrained comparing with non-supplemented untrained group. Gene expression of gluconeogenesis regulatory factors was increased by training and reduced by HMB supplementation. These results confirm that HMB supplementation associated with intensive training protocol drives changes in glucose homeostasis and liver metabolism in mice.

Clinical and Experimental Analysis of 201Thallium Uptake of the Heart

1978 ◽  
Vol 17 (04) ◽  
pp. 142-148
Author(s):  
U. Büll ◽  
S. Bürger ◽  
B. E. Strauer
Keyword(s):  
Oxygen Consumption ◽  
Left Ventricle ◽  
Muscle Mass ◽  
Myocardial Oxygen Consumption ◽  
Animal Experiments ◽  
Left Ventricular ◽  
Left Ventricular Wall ◽  
Ventricular Wall ◽  
Flow Measurements ◽  
Myocardial Flow

Studies were carried out in order to determine the factors influencing myocardial 201T1 uptake. A total of 158 patients was examined with regard to both 201T1 uptake and the assessment of left ventricular and coronary function (e. g. quantitative ventriculography, coronary arteriography, coronary blood flow measurements). Moreover, 42 animal experiments (closed chest cat) were performed. The results demonstrate that:1) 201T1 uptake in the normal and hypertrophied human heart is linearly correlated with the muscle mass of the left ventricle (LVMM);2) 201T1 uptake is enhanced in the inner (subendocardial) layer and is decreased in the outer (subepicardial) layer of the left ventricular wall. The 201T1 uptake of the right ventricle is 40% lower in comparison to the left ventricle;3) the basic correlation between 201T1 uptake and LVMM is influenced by alterations of both myocardial flow and myocardial oxygen consumption; and4) inotropic interventions (isoproterenol, calcium, norepinephrine) as well as coronary dilatation (dipyridamole) may considerably augment 201T1 uptake in accordance with changes in myocardial oxygen consumption and/or myocardial flow.It is concluded that myocardial 201T1 uptake is determined by multiple factors. The major determinants have been shown to include (i) muscle mass, (ii) myocardial flow and (iii) myocardial oxygen consumption. The clinical data obtained from patient groups with normal ventricular function, with coronary artery disease, with left ventricular wall motion abnormalities and with different degree of left ventricular hypertrophy are correlated with quantitated myocardial 201T1 uptake.

Improvement of muscle mass and force by certain hormones and endogen factors, contributing in muscle development

2007 ◽  
Vol 148 (10) ◽  
pp. 451-456
Author(s):  
Péter Apor ◽  
József Tihanyi ◽  
Andreas Costa
Keyword(s):  
Muscle Mass ◽  
Muscle Development

Az áttekintés az izomtömeg és az izomerő növelése célzatával alkalmazott hormonok (növekedési hormon, IGF-1, anabolikus-androgén szteroidok) és az izom fejlődésében szereplő, humán használatra kerülhető egyes faktorok fizikai aktivitással kapcsolatos élettanát és klinikai alkalmazásának lehetőségeit érinti. A hatásokat illetően mítoszok, a mellékhatásokat illetően alul- és túlértesültség egyaránt jellemzi e területet. A kórállapotok sorában, s nem csak a hiányállapotok szubsztitúciójában történnek terápiás próbálkozások, amelyekben figyelembe vehetők a sportolók, testépítők tapasztalatai is.

Sign in / Sign up

Export Citation Format

Share Document