scholarly journals Management of Respiratory Depression with Acetate Solution and High-Fat Diet in Patient with Congenital Defect of Pyruvate Dehydrogenase Activity

1997 ◽  
Vol 4 (1) ◽  
pp. 53-58
Author(s):  
Osamu Nagata ◽  
Yoshihiko Mizuno ◽  
Yuko Harikae ◽  
Hideto Nakayama
Keyword(s):  
Dehydrogenase Activity ◽  
Respiratory Depression ◽  
Pyruvate Dehydrogenase ◽  
High Fat Diet ◽  
Congenital Defect ◽  
Acetate Solution ◽  
High Fat

scholarly journals Regulation of pyruvate dehydrogenase and pyruvate dehydrogenase phosphate phosphatase activity in rat epididymal fat-pads. Effects of starvation, alloxan-diabetes and high-fat diet

1976 ◽  
Vol 154 (1) ◽  
pp. 225-236 ◽  
Author(s):  
D Stansbie ◽  
R M Denton ◽  
B J Bridges ◽  
H T Pask ◽  
P J Randle
Keyword(s):  
Phosphatase Activity ◽  
Dehydrogenase Activity ◽  
Pyruvate Dehydrogenase ◽  
High Fat Diet ◽  
Alloxan Diabetes ◽  
Mitochondrial Activity ◽  
High Fat ◽  
Epididymal Fat ◽  
Fat Pads

1. Pyruvate dehydrogenase phosphate phosphatase activity in rat epididymal fat-pads was measured by using pig heart pyruvate dehydrogenase [32P]phosphate. About 80% was found to be extramitochondrial and therefore probably not directly concerned with the regulation of pyruvate dehydrogenase activity. The extramitochondrial activity was sensitive to activation by +, but perhaps less sensitive than the mitochondrial activity.

Elevated n-3 fatty acids in a high-fat diet attenuate the increase in PDH kinase activity but not PDH activity in human skeletal muscle

2005 ◽  
Vol 98 (1) ◽  
pp. 350-355 ◽  
Author(s):  
Erin A. Turvey ◽  
George J. F. Heigenhauser ◽  
Michelle Parolin ◽  
Sandra J. Peters
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Pyruvate Dehydrogenase ◽  
High Fat Diet ◽  
Human Skeletal Muscle ◽  
Fat Content ◽  
Pyruvate Dehydrogenase Kinase ◽  
High Fat ◽  
High Fat Diets ◽  
Fat Diets

We tested the hypothesis that a high-fat diet (75% fat; 5% carbohydrates; 20% protein), for which 15% of the fat content was substituted with n-3 fatty acids, would not exhibit the diet-induced increase in pyruvate dehydrogenase kinase (PDK) activity, which is normally observed in human skeletal muscle. The fat content was the same in both the regular high-fat diet (HF) and in the n-3-substituted diet (N3). PDK activity increased after both high-fat diets, but the increase was attenuated after the N3 diet (0.051 ± 0.007 and 0.218 ± 0.047 min−1 for pre- and post-HF, respectively; vs. 0.073 ± 0.016 and 0.133 ± 0.032 min−1 for pre- and post-N3, respectively). However, the active form of pyruvate dehydrogenase (PDHa) activity decreased to a similar extent in both conditions (0.93 ± 0.17 and 0.43 ± 0.09 mmol/kg wet wt pre- and post-HF; vs. 0.87 ± 0.19 and 0.39 ± 0.05 mmol/kg wet wt pre- and post-N3, respectively). This suggested that the difference in PDK activity did not affect PDHa activation in the basal state, and it was regulated by intramitochondrial effectors, primarily muscle pyruvate concentration. Muscle glycogen content was consistent throughout the study, before and after both diet conditions, whereas muscle glucose-6-phosphate, glycerol-3-phosphate, lactate, and pyruvate were decreased after the high-fat diets. Plasma triglycerides decreased after both high-fat diets but decreased to a greater extent after the N3, whereas plasma free fatty acids increased after both diets, but to a lesser extent after the N3. In summary, PDK activity is decreased after a high-fat diet that is rich in n-3 fatty acids, although PDHa activity was unaltered. In addition, our data demonstrated that the hypolipidemic effect of n-3 fatty acids occurs earlier (3 days) than previously reported and is evident even when the diet has 75% of its total energy derived from fat.

scholarly journals Pyruvate dehydrogenase kinase-4 deficiency lowers blood glucose and improves glucose tolerance in diet-induced obese mice

2008 ◽  
Vol 295 (1) ◽  
pp. E46-E54 ◽  
Author(s):  
Nam Ho Jeoung ◽  
Robert A. Harris
Keyword(s):  
Skeletal Muscle ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Pyruvate Dehydrogenase ◽  
High Fat Diet ◽  
Pyruvate Dehydrogenase Kinase ◽  
Wild Type ◽  
High Fat ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
Liver And Kidney

The effect of pyruvate dehydrogenase kinase-4 (PDK4) deficiency on glucose homeostasis was studied in mice fed a high-fat diet. Expression of PDK4 was greatly increased in skeletal muscle and diaphragm but not liver and kidney of wild-type mice fed the high-fat diet. Wild-type and PDK4−/− mice consumed similar amounts of the diet and became equally obese. Insulin resistance developed in both groups. Nevertheless, fasting blood glucose levels were lower, glucose tolerance was slightly improved, and insulin sensitivity was slightly greater in the PDK4−/− mice compared with wild-type mice. When the mice were killed in the fed state, the actual activity of the pyruvate dehydrogenase complex (PDC) was higher in the skeletal muscle and diaphragm but not in the liver and kidney of PDK4−/− mice compared with wild-type mice. When the mice were killed after overnight fasting, the actual PDC activity was higher only in the kidney of PDK4−/− mice compared with wild-type mice. The concentrations of gluconeogenic substrates were lower in the blood of PDK4−/− mice compared with wild-type mice, consistent with reduced formation in peripheral tissues. Diaphragms isolated from PDK4−/− mice oxidized glucose faster and fatty acids slower than diaphragms from wild-type mice. Fatty acid oxidation inhibited glucose oxidation by diaphragms from wild-type but not PDK4−/− mice. NEFA, ketone bodies, and branched-chain amino acids were elevated more in PDK4−/− mice, consistent with slower rates of oxidation. These findings show that PDK4 deficiency lowers blood glucose and slightly improves glucose tolerance and insulin sensitivity in mice with diet-induced obesity.

scholarly journals Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise

2004 ◽  
Vol 63 (2) ◽  
pp. 221-226 ◽  
Author(s):  
Henriette Pilegaard ◽  
P. Darrell Neufer
Keyword(s):  
Skeletal Muscle ◽  
Muscle Glycogen ◽  
Pyruvate Dehydrogenase ◽  
High Fat Diet ◽  
Prolonged Exercise ◽  
Pyruvate Dehydrogenase Kinase ◽  
High Fat ◽  
Low Intensity ◽  
Low Intensity Exercise ◽  
The Impact

The pyruvate dehydrogenase complex (PDC) has a key position in skeletal muscle metabolism as it represents the entry of carbohydrate-derived fuel into the mitochondria for oxidation. PDC is regulated by a phosphorylation–dephosphorylation cycle, in which the pyruvate dehydrogenase kinase (PDK) phosphorylates and inactivates the complex. PDK exists in four isoforms, of which the PDK4 isoform is predominantly expressed in skeletal and heart muscle. PDK4 transcription and PDK4 mRNA are markedly increased in human skeletal muscle during prolonged exercise and after both short-term high-intensity and prolonged low-intensity exercise. The exercise-induced transcriptional response of PDK4 is enhanced when muscle glycogen is lowered before the exercise, and intake of a low-carbohydrate high-fat diet during recovery from exercise results in increased transcription and mRNA content of PDK4 when compared with intake of a high-carbohydrate diet. The activity of pyruvate dehydrogenase (PDH) is increased during the first 2 h of low-intensity exercise, followed by a decrease towards resting levels, which is in line with the possibility that the increased PDK4 expressed influences the PDH activity already during prolonged exercise. PDK4 expression is also increased in response to fasting and a high-fat diet. Thus, increased PDK4 expression when carbohydrate availability is low seems to contribute to the sparing of carbohydrates by preventing carbohydrate oxidation. The impact of substrate availability on PDK4 expression during recovery from exercise also underlines the high metabolic priority given to replenishing muscle glycogen stores and re-establishing intracellular homeostasis after exercise.

Abstract 18910: Angiotensin Converting Enzyme 2 Deficiency Results in Cardiac Insulin Resistance in Response to High-Fat Diet

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Vaibhav B Patel ◽  
Jun Mori ◽  
Brent A McLean ◽  
Gary D Lopaschuk ◽  
Gavin Y Oudit
Keyword(s):  
Insulin Resistance ◽  
Insulin Signaling ◽  
Pyruvate Dehydrogenase ◽  
High Fat Diet ◽  
Renin Angiotensin System ◽  
Cardiac Metabolism ◽  
Converting Enzyme ◽  
High Fat ◽  
Angiotensin System ◽  
Cardiac Energy

Background: Activation of the renin-angiotensin system (RAS) can alter the cardiac energy substrate preference, thereby contributing to the progression of heart failure. Angiotensin converting enzyme (ACE) 2 is a key negative regulator of the RAS where it metabolizes angiotensin (Ang) II into Ang (1-7). Hypothesis: Myocardial ACE2 was upregulated in response to high-fat diet in wildtype (WT) mice. We hypothesize that ACE2 upregulation is a compensatory response and loss of ACE2 will worsened obesity and its associated cardiomyopathy. Methods and Results: ACE2-null (ACE2-/y; ACE2KO) and WT litter-mate control mice were fed with high-fat diet (HFD; 45 kcal%) or control diet (10 kcal%) and studied at 6-months of age. In contrast to our hypothesis, loss of ACE2 resulted in decreased obesity in response to HFD compared to WT mice (body weight at 6-months: 45.9±4.3 in ACE2KO-HFD vs 51.4±1.55 in WT-HFD; p<0.05). Conversely, ACE2KO-HFD mice showed increased fasting plasma glucose levels (6.76±0.7 in ACE2KO-HFD vs 5.11±0.6 in WT-HFD; p<0.05) with worsened whole-body insulin resistance. We subjected hearts to ex vivo aerobic perfusions to measure cardiac energy metabolism. ACE2KO-HFD hearts showed markedly decreased cardiac work along with reduced insulin response suggesting increased myocardial insulin resistance. ACE2KO-HFD hearts relied predominantly on fat metabolism as the energy source, a feature observed in cardiomyopathy. Pressure-volume analysis showed worsened diastolic dysfunction in the ACE2KO hearts compared to WT hearts in response to HFD, which was primarily due to impaired active relaxation (Tau(Weiss): 7.41±0.4 in ACE2KO-HFD vs 6.26±0.52 in WT-HFD; p<0.05). Metabolic and functional changes in the ACE2KO-HFD were associated with impaired insulin signaling (decreased p-Akt) and decreased phosphorylation of AMPK. ACE2KO-HFD hearts also showed increased pyruvate dehydrogenase kinase 4 expression and phosphorylation of pyruvate dehydrogenase. Conclusions: Renin-angiotensin system plays an important role in cardiac metabolism. We found a novel role of ACE2 in cardiac insulin signaling, where ACE2 negatively regulates obesity and hyperglycemia induced cardiac insulin-resistance and alterations in cardiac metabolism.

Pyruvate and hepatic pyruvate dehydrogenase levels in rat strains sensitive and resistant to dietary obesity

1996 ◽  
Vol 270 (3) ◽  
pp. R489-R495 ◽  
Author(s):  
H. Nagase ◽  
G. A. Bray ◽  
D. A. York
Keyword(s):  
Pyruvate Dehydrogenase ◽  
High Fat Diet ◽  
Serum Levels ◽  
High Fat ◽  
Low Fat ◽  
Rat Strains ◽  
Diet Induced Obesity ◽  
Dietary Obesity ◽  
Ad Libitum ◽  
Fat Diets

This study compared the effects of exogenous pyruvate and lactate on the serum levels of pyruvate, lactate, glucose, alanine, and insulin, as well as the activity of hepatic pyruvate dehydrogenase (PDH) in strains of rat that were either sensitive [Osborne-Mendel (OM)] or resistant (S5B/Pl) to high-fat diet-induced obesity. Serum pyruvate and lactate were significantly higher and glucose lower in ad libitum-fed OM rats, but these differences disappeared after an 18-h fast. The increase in pyruvate and lactate after exogenous pyruvate administration was significantly greater in S5B/Pl rats than OM rats. There were no differences in serum alanine with strain or diet. The total PDH activity was similar across strains and diets but the proportion of PDH in its activated form (PDHa) was decreased in ad libitum-fed S5B/Pl rats. Pyruvate injection increased insulin and hepatic PDHa activity in OM rats fed both high- and low-fat diets, but these responses were greatly attenuated or absent in S5B/Pl rats. The data are consistent with the hypothesis that modulation of carbohydrate oxidation by PDH may be related to susceptibility to obesity when rats are fed a high-fat diet.

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