Effect of repetitive stunning on myocardial metabolism in pig hearts

1997 ◽  
Vol 273 (3) ◽  
pp. H1395-H1402 ◽  
Author(s):  
T. A. Hacker ◽  
B. Renstrom ◽  
S. H. Nellis ◽  
A. J. Liedtke
Keyword(s):  
Animal Studies ◽  
Glucose Utilization ◽  
Initial Conditions ◽  
Acid Oxidation ◽  
Mechanical Function ◽  
Short Term ◽  
Progressive Decline ◽  
Myocardial O2 Consumption ◽  
Animal Preparation ◽  
Chronic Hibernation

Recent animal and clinical studies have suggested that chronic hibernation, a condition of depressed mechanical function and enhanced glycolysis in viable but downregulated myocardium, may result from chronic repetitive ischemia and reperfusion. The present study was conducted to test whether similar trends could be reproduced in an acute animal preparation of repetitive stunning. Eight intact pig hearts were extracorporeally perfused for 115 min and subjected to four cycles of ischemia [60% decrease in anterior descending flow for 5 min each, interspersed with 15 min of aerobic reperfusion]. Each bout of ischemia caused a progressive decline in regional systolic shortening such that systolic shortening was 37% lower at end-reperfusion (P < 0.05 vs. initial conditions). Regional myocardial O2 consumption was reduced during ischemia but was not significantly lower at end-reperfusion compared with that under initial conditions. Fatty acid oxidation was unchanged at any point during the trials. Although glucose utilization was increased by an average of 264% during the four ischemic periods, it was not significantly or progressively increased during the reperfusion periods. Therefore, although this acute stunning protocol depressed mechanical function, it did not cumulatively increase glycolysis during reperfusion. This absence of accelerated glycolysis is at variance with the metabolic findings reported in clinical hibernation and raises concerns regarding this protocol in animal studies designed to simulate short-term hibernation.

Glucose and fatty acid metabolism in the isolated working mouse heart

1999 ◽  
Vol 277 (4) ◽  
pp. R1210-R1217 ◽  
Author(s):  
Darrell D. Belke ◽  
Terje S. Larsen ◽  
Gary D. Lopaschuk ◽  
David L. Severson
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
Acid Metabolism ◽  
Acid Oxidation ◽  
Mouse Heart ◽  
Mechanical Function ◽  
Substrate Metabolism ◽  
Cardiac Power ◽  
Rat Hearts

Although isolated perfused mouse heart models have been developed to study mechanical function, energy substrate metabolism has not been examined despite the expectation that the metabolic rate for a heart from a small mammal should be increased. Consequently, glucose utilization (glycolysis, oxidation) and fatty acid oxidation were measured in isolated working mouse hearts perfused with radiolabeled substrates, 11 mM glucose, and either 0.4 or 1.2 mM palmitate. Heart rate, coronary flow, cardiac output, and cardiac power did not differ significantly between hearts perfused at 0.4 or 1.2 mM palmitate. Although the absolute values obtained for glycolysis and glucose oxidation and fatty acid oxidation are significantly higher than those reported for rat hearts, the pattern of substrate metabolism in mouse hearts is similar to that observed in hearts from larger mammals. The metabolism of mouse hearts can be altered by fatty acid concentration in a manner similar to that observed in larger animals; increasing palmitate concentration altered the balance of substrate metabolism to increase overall energy derived from fatty acids from 64 to 92%.

scholarly journals Systems-wide effects of short-term feed deprivation in obese mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel Andersen ◽  
Henrik Munch Roager ◽  
Li Zhang ◽  
Janne Marie Moll ◽  
Henrik Lauritz Frandsen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Butyric Acid ◽  
Visceral Adipose Tissue ◽  
Animal Studies ◽  
Uncoupling Protein ◽  
Metabolic Changes ◽  
Obese Mice ◽  
Short Term ◽  
Feed Deprivation ◽  
Visceral Adipose

AbstractWhile prolonged fasting induces significant metabolic changes in humans and mice, less is known about systems-wide metabolic changes in response to short-term feed deprivation, which is used in experimental animal studies prior to metabolic challenge tests. We here performed a systems biology-based investigation of connections between gut bacterial composition and function, inflammatory and metabolic parameters in the intestine, liver, visceral adipose tissue, blood and urine in high-fat fed, obese mice that were feed deprived up to 12 h. The systems-wide analysis revealed that feed deprivation linked to enhanced intestinal butyric acid production and expression of the gene encoding the pro-thermogenic uncoupling protein UCP1 in visceral adipose tissue of obese mice. Ucp1 expression was also positively associated with Il33 expression in ileum, colon and adipose tissue as well as with the abundance of colonic Porphyromonadaceae, the latter also correlating to cecal butyric acid levels. Collectively, the data highlighted presence of a multi-tiered system of inter-tissue communication involving intestinal, immune and metabolic functions which is affected by feed deprivation in obese mice, thus pointing to careful use of short-feed deprivation in metabolic studies using obese mice.

scholarly journals Implementation of a 3-D-Var system for atmospheric profiling data assimilation into the RAMS model: initial results

2013 ◽  
Vol 6 (2) ◽  
pp. 3581-3610
Author(s):  
S. Federico
Keyword(s):  
Relative Humidity ◽  
Data Assimilation ◽  
Initial Conditions ◽  
Weather Prediction ◽  
Wind Profiler ◽  
Short Term ◽  
Recursive Filters ◽  
Data Assimilation System ◽  
Rams Model ◽  
Assimilation System

Abstract. This paper presents the current status of development of a three-dimensional variational data assimilation system. The system can be used with different numerical weather prediction models, but it is mainly designed to be coupled with the Regional Atmospheric Modelling System (RAMS). Analyses are given for the following parameters: zonal and meridional wind components, temperature, relative humidity, and geopotential height. Important features of the data assimilation system are the use of incremental formulation of the cost-function, and the use of an analysis space represented by recursive filters and eigenmodes of the vertical background error matrix. This matrix and the length-scale of the recursive filters are estimated by the National Meteorological Center (NMC) method. The data assimilation and forecasting system is applied to the real context of atmospheric profiling data assimilation, and in particular to the short-term wind prediction. The analyses are produced at 20 km horizontal resolution over central Europe and extend over the whole troposphere. Assimilated data are vertical soundings of wind, temperature, and relative humidity from radiosondes, and wind measurements of the European wind profiler network. Results show the validity of the analysis solutions because they are closer to the observations (lower RMSE) compared to the background (higher RMSE), and the differences of the RMSEs are consistent with the data assimilation settings. To quantify the impact of improved initial conditions on the short-term forecast, the analyses are used as initial conditions of a three-hours forecast of the RAMS model. In particular two sets of forecasts are produced: (a) the first uses the ECMWF analysis/forecast cycle as initial and boundary conditions; (b) the second uses the analyses produced by the 3-D-Var scheme as initial conditions, then is driven by the ECMWF forecast. The improvement is quantified by considering the horizontal components of the wind, which are measured at a-synoptic times by the European wind profiler network. The results show that the RMSE is effectively reduced at the short range (1–2 h). The results are in agreement with the set-up of the numerical experiment.

scholarly journals 2-Deoxy-d-glucose, but not mercaptoacetate, increases food intake in decerebrate rats

2009 ◽  
Vol 297 (2) ◽  
pp. R382-R386 ◽  
Author(s):  
Rebecca A. Darling ◽  
Sue Ritter
Keyword(s):  
Fatty Acid ◽  
Food Intake ◽  
Food Consumption ◽  
Sensory Neurons ◽  
Glucose Utilization ◽  
Milk Intake ◽  
Acid Oxidation ◽  
Neural Pathways ◽  
Test Diet ◽  
Vagal Afferent

We examined food intake in chronically maintained decerebrate rats in response to two antimetabolic drugs known to stimulate food intake, 2-mercaptoacetate (MA) and 2-deoxy-d-glucose (2DG). MA reduces fatty acid oxidation, and 2DG reduces glucose utilization. Because previous work has shown that insulin-induced hypoglycemia increases food intake in decerebrate rats, we predicted that 2DG would have this same effect. MA-induced feeding requires vagal sensory neurons that terminate in the hindbrain. Cholecystokinin-induced suppression of feeding, which likewise requires vagal sensory neurons, has been shown to suppress food intake in decerebrate rats. Therefore, we predicted that MA's effects on feeding would also persist in decerebrate rats. In our experiments, the test diet (40% milk, diluted with water) was infused intraorally through a chronic cheek fistula. We found that sham controls consumed 258% and 230% of their baseline milk intake in response to 2DG and MA, respectively. Decerebrates consumed 239% of their baseline milk intake in response to 2DG, but did not increase their intake in response to MA. Because decerebration separates the hindbrain from the forebrain, these results indicate that 2DG-induced glucoprivation is capable of acting within the hindbrain to activate fundamental reflex circuitry for consummatory feeding responses, as shown previously for hypoglycemia. In contrast, MA affects food consumption only after forebrain processing of MA-induced vagal afferent signals and in the presence of intact ascending and descending neural pathways.

scholarly journals Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-induced Weight Gain in Male Mice

2020 ◽  
Author(s):  
E. Matthew Morris ◽  
Roberto D. Noland ◽  
Michael E. Ponte ◽  
Michelle L. Montonye ◽  
Julie A. Christianson ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Weight Gain ◽  
Energy Metabolism ◽  
Energy Balance ◽  
Fatty Acid Oxidation ◽  
Positive Energy ◽  
Acid Oxidation ◽  
Male Mice ◽  
Short Term

AbstractCentral integration of peripheral neural signals is one mechanism by which systemic energy homeostasis is regulated. Previous work described increased acute food intake following chemical reduction of hepatic fatty acid oxidation and ATP levels, which was prevented by common hepatic branch vagotomy (HBV). However, possible offsite actions of the chemical compounds confound the precise role of liver energy metabolism. Herein, we used a liver-specific PGC1a heterozygous (LPGC1a) mouse model, with associated reductions in mitochondrial fatty acid oxidation and respiratory capacity, to assess the role of liver energy metabolism in systemic energy homeostasis. LPGC1a male mice have 70% greater high-fat/high-sucrose (HFHS) diet-induced weight gain and 35% greater positive energy balance compared to wildtype (WT) (p<0.05). The greater energy balance was associated with altered feeding behavior and lower activity energy expenditure during HFHS in LPGC1a males. Importantly, no differences in HFHS-induced weight gain or energy metabolism was observed between female WT and LPGC1a mice. WT and LPGC1a mice underwent sham or HBV to assess whether vagal signaling was involved in HFHS-induced weight gain of male LPGC1a mice. HBV increased HFHS-induced weight gain (85%, p<0.05) in male WT, but not LPGC1a mice. As above, sham LPGC1a males gain 70% more weight during short-term HFHS feeding than sham WT (p<0.05). These data demonstrate a sexspecific role of reduced liver energy metabolism in acute diet-induced weight gain, and the need of more nuanced assessment of the role of vagal signaling in short-term diet-induced weight gain.Key Points SummaryReduced liver PGC1a expression results in reduced mitochondrial fatty acid oxidation and respiratory capacity in male mice.Male mice with reduced liver PGC1a expression (LPGC1a) demonstrate greater short-term high-fat/high-sucrose diet-induced weight gain compared to wildtype.Greater positive energy balance during HFHS feeding in male LPGC1a mice is associated with altered food intake patterns and reduced activity energy expenditure.Female LPGC1a mice do not have differences in short-term HFHS-induced body weight gain or energy metabolism compared to wildtype.Disruption of vagal signaling through common hepatic branch vagotomy increases short-term HFHS-induced weight gain in male wildtype mice, but does not alter male LPGC1a weight gain.

Abstract 344: FNDC5, a PGC1-a-Dependent Myokine, Increases Glucose Utilization and Fatty-Acid Oxidation by AMPK Signaling Pathway

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Ling Tao ◽  
Yi Liu ◽  
Chao Xin ◽  
Weidong Huang ◽  
Lijian Zhang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Uptake ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
C2c12 Cells ◽  
Time Dependent ◽  
Acid Oxidation ◽  
Ampk Signaling

FNDC5 is a hormone secreted by myocytes that could reduce obesity and insulin resistance, However, the exact effect of FNDC5 on glucose and lipid metabolism remain poorly identified; More importantly, the signaling pathways that mediate the metabolic effects of FNDC5 is completely unknown. Here we showed that FNDC5 stimulates β-oxidation and glucose uptake in C2C12 cells in a dose- and time-dependent fashion in vitro (n=8, all P<0.01). In vivo study revealed that FNDC5 also enhanced glucose tolerance in diabetic mice and increased the glucose uptake evidenced by increased [18F] FDG accumulation in hearts by PET scan (n=6, all P<0.05). FNDC5 decreased the expression of gluconeogenesis related molecules (PEPCK and G6Pase) and increased the phosphorylation of ACC, a key modulator of fatty-acid oxidation, both in hepatocytes and C2C12 cells (n=3, all P<0.05). In parallel with its stimulation of β-oxidation and glucose uptake, FNDC5 increased the phosphorylation of AMPK both in hepatocytes and C2C12 cells in a dose- and time-dependent fashion in vitro and in vivo. More importantly, the β-oxidation and glucose uptake, the expression of PEPCK and G6Pase and the phosphorylation of ACC induced by FNDC5 were attenuated by AMPK inhibitor in hepatocytes and C2C12 cells (P<0.05). Most importantly, the FNDC5 induced glucose uptake and phosphorylation of ACC were attenuated in AMPK-DN mice (n=6, all P<0.05). The glucose-lowering effect of FNDC5 in diabetic mice was also attenuated by AMPK inhibitor. Our data presents the direct evidence that FNDC5 stimulates glucose utilization and fatty-acid oxidation by AMPK signaling pathway, suggesting that FNDC5 be a novel pharmacological approach for type 2 diabetes.

scholarly journals A Two-Season Impact Study of Radiative Forced Tropospheric Response to Stratospheric Initial Conditions Inferred From Satellite Radiance Assimilation

Climate ◽  
2019 ◽  
Vol 7 (9) ◽  
pp. 114
Author(s):  
Min Shao ◽  
Yansong Bao ◽  
George P. Petropoulos ◽  
Hongfang Zhang
Keyword(s):  
Weather Forecasting ◽  
Initial Conditions ◽  
Stratospheric Ozone ◽  
Wrf Model ◽  
Lower Troposphere ◽  
Short Wave ◽  
Advanced Technology ◽  
Short Term ◽  
Radiative Processes ◽  
Stratospheric Temperature

This study investigated the impacts of stratospheric temperatures and their variations on tropospheric short-term weather forecasting using the Advanced Research Weather Research and Forecasting (WRF-ARW) system with real satellite data assimilation. Satellite-borne microwave stratospheric temperature measurements up to 1 mb, from the Advanced Microwave Sounding Unit-A (AMSU-A), the Advanced Technology Microwave Sounder (ATMS), and the Special Sensor microwave Imager/Sounder (SSMI/S), were assimilated into the WRF model over the continental U.S. during winter and summer 2015 using the community Gridpoint Statistical Interpolation (GSI) system. Adjusted stratospheric temperature related to upper stratospheric ozone absorption of short-wave (SW) radiation further lead to vibration in downward SW radiation in winter predictions and overall reduced with a maximum of 5.5% reduction of downward SW radiation in summer predictions. Stratospheric signals in winter need 48- to 72-h to propagate to the lower troposphere while near-instant tropospheric response to the stratospheric initial conditions are observed in summer predictions. A schematic plot illustrated the physical processes of the coupled stratosphere and troposphere related to radiative processes. Our results suggest that the inclusion of the entire stratosphere and better representation of the upper stratosphere are important in regional NWP systems in short-term forecasts.

scholarly journals Activated AMPK inhibits PPAR-α and PPAR-γ transcriptional activity in hepatoma cells

2011 ◽  
Vol 301 (4) ◽  
pp. G739-G747 ◽  
Author(s):  
Margaret S. Sozio ◽  
Changyue Lu ◽  
Yan Zeng ◽  
Suthat Liangpunsakul ◽  
David W. Crabb
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Luciferase Reporter ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Short Term ◽  
Reporter Activity ◽  
Ppar Γ ◽  
Compound C ◽  
Α Activity

AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-α (PPAR-α) are critical regulators of short-term and long-term fatty acid oxidation, respectively. We examined whether the activities of these molecules were coordinately regulated. H4IIEC3 cells were transfected with PPAR-α and PPAR-γ expression plasmids and a peroxisome-proliferator-response element (PPRE) luciferase reporter plasmid. The cells were treated with PPAR agonists (WY-14,643 and rosiglitazone), AMPK activators 5-aminoimidazole-4-carboxamide riboside (AICAR) and metformin, and the AMPK inhibitor compound C. Both AICAR and metformin decreased basal and WY-14,643-stimulated PPAR-α activity; compound C increased agonist-stimulated reporter activity and partially reversed the effect of the AMPK activators. Similar effects on PPAR-γ were seen, with both AICAR and metformin inhibiting PPRE reporter activity. Compound C increased basal PPAR-γ activity and rosiglitazone-stimulated activity. In contrast, retinoic acid receptor-α (RAR-α), another nuclear receptor that dimerizes with retinoid X receptor (RXR), was largely unaffected by the AMPK activators. Compound C modestly increased AM580 (an RAR agonist)-stimulated activity. The AMPK activators did not affect PPAR-α binding to DNA, and there was no consistent correlation between effects of the AMPK activators and inhibitor on PPAR and the nuclear localization of AMPK-α subunits. Expression of either a constitutively active or dominant negative AMPK-α inhibited basal and WY-14,643-stimulated PPAR-α activity and basal and rosiglitazone-stimulated PPAR-γ activity. We concluded that the AMPK activators AICAR and metformin inhibited transcriptional activities of PPAR-α and PPAR-γ, whereas inhibition of AMPK with compound C activated both PPARs. The effects of AMPK do not appear to be mediated through effects on RXR or on PPAR/RXR binding to DNA. These effects are independent of kinase activity and instead appear to rely on the activated conformation of AMPK. AMPK inhibition of PPAR-α and -γ may allow for short-term processes to increase energy generation before the cells devote resources to increasing their capacity for fatty acid oxidation.

Effects of blockade of fatty acid oxidation on whole body and tissue-specific glucose metabolism in rats

1993 ◽  
Vol 265 (4) ◽  
pp. E592-E600 ◽  
Author(s):  
A. B. Jenkins ◽  
L. H. Storlien ◽  
G. J. Cooney ◽  
G. S. Denyer ◽  
I. D. Caterson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Glucose Metabolism ◽  
Fatty Acid Oxidation ◽  
Pyruvate Dehydrogenase ◽  
Glucose Utilization ◽  
Whole Body ◽  
Acid Oxidation ◽  
Tissue Specific ◽  
Glucose Output

We examined the effect of the long-chain fatty acid oxidation blocker methyl palmoxirate (methyl 2-tetradecyloxiranecarboxylate, McN-3716) on glucose metabolism in conscious rats. Fasted animals [5 h with or without hyperinsulinemia (100 mU/l) and 24 h] received methyl palmoxirate (30 or 100 mg/kg body wt po) or vehicle 30 min before a euglycemic glucose clamp. Whole body and tissue-specific glucose metabolism were calculated from 2-deoxy-[3H]-glucose kinetics and accumulation. Oxidative metabolism was assessed by respiratory gas exchange in 24-h fasted animals. Pyruvate dehydrogenase complex activation was determined in selected tissues. Methyl palmoxirate suppressed whole body lipid oxidation by 40-50% in 24-h fasted animals, whereas carbohydrate oxidation was stimulated 8- to 10-fold. Whole body glucose utilization was not significantly affected by methyl palmoxirate under any conditions; hepatic glucose output was suppressed only in the predominantly gluconeogenic 24-h fasted animals. Methyl palmoxirate stimulated glucose uptake in heart in 24-h fasted animals [15 +/- 5 vs. 220 +/- 28 (SE) mumol x 100 g-1 x min-1], with smaller effects in 5-h fasted animals with or without hyperinsulinemia. Methyl palmoxirate induced significant activation of pyruvate dehydrogenase in heart in the basal state, but not during hyperinsulinemia. In skeletal muscles, methyl palmoxirate suppressed glucose utilization in the basal state but had no effect during hyperinsulinemia; pyruvate dehydrogenase activation in skeletal muscle was not affected by methyl palmoxirate under any conditions. The responses in skeletal muscle are consistent with the operation of a mechanism similar to the Pasteur effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial metabolism in chronic reperfusion after nontransmural infarction in pig hearts

1993 ◽  
Vol 265 (5) ◽  
pp. H1614-H1622
Author(s):  
A. J. Liedtke ◽  
B. Renstrom ◽  
S. H. Nellis ◽  
R. Subramanian ◽  
G. Woldegiorgis
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
Myocardial Metabolism ◽  
Respiratory Control ◽  
Acid Oxidation ◽  
Membrane Transporter ◽  
Exogenous Glucose ◽  
14Co2 Production ◽  
Metabolic Behavior

The purpose of these studies was to evaluate metabolic behavior in a 4-day reperfusion model in pigs after induction of subendocardial infarction. Two groups of swine [sham and intervention (Int) groups, n = 7) and 10 hearts per group, respectively] were prepared comparably with two surgical procedures separated over 4 days. In the Int group at the time of the first surgery, coronary flow in the left anterior descending (LAD) circulation was partially restricted (by 60%) for 60 min and was then reperfused. LAD myocardium at the time of the second surgery in both groups was extracorporeally perfused aerobically (5.9 +/- 0.2 ml.min-1.g dry wt-1) for 60 min and infused by equilibrium labeling with [U-14C]-palmitate and [5-3H]glucose to estimate fatty acid oxidation and exogenous glucose utilization. During extracorporeal perfusion, regional myocardial shortening and oxygen consumption were comparable between groups despite a marginal impairment in ATP resynthesis by mitochondria (26% decrease, P < 0.071) in Int hearts and a significant decline in mitochondrial respiration (45% decrease in respiratory control rate, P < 0.008; and 41% decrease in state 3 respiration, P < 0.032) as compared with sham hearts. Fatty acid oxidation described by 14CO2 production was 34.00 +/- 4.72 mumol.h-1.g dry wt-1 (averaged from 30-60 min of perfusion) in sham hearts but was decreased (by 48%, P < 0.004) in Int hearts. This reduction in fatty acid utilization may in part be explained by declines in the observed activity of the mitochondrial membrane transporter enzyme, carnitine palmitoyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

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