scholarly journals Effect of acute exercise on uncoupling protein 3 is a fat metabolism-mediated effect

2002 ◽  
Vol 282 (1) ◽  
pp. E11-E17 ◽  
Author(s):  
Patrick Schrauwen ◽  
Matthijs K. C. Hesselink ◽  
Ilonca Vaartjes ◽  
Esther Kornips ◽  
Wim H. M. Saris ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Mrna Expression ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Acute Exercise ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Fasted State ◽  
Glucose Ingestion ◽  
Plasma Ffa

Human and rodent uncoupling protein (UCP)3 mRNA is upregulated after acute exercise. Moreover, exercise increases plasma levels of free fatty acid (FFA), which are also known to upregulate UCP3. We investigated whether the upregulation of UCP3 after exercise is an effect of exercise per se or an effect of FFA levels or substrate oxidation. Seven healthy untrained men [age: 22.7 ± 0.6 yr; body mass index: 23.8 ± 1.0 kg/m2; maximal O2 uptake (V˙o 2 max): 3,852 ± 211 ml/min] exercised at 50% V˙o 2 max for 2 h and then rested for 4 h. Muscle biopsies and blood samples were taken before and immediately after 2 h of exercise and 1 and 4 h in the postexercise period. To modulate plasma FFA levels and fat/glucose oxidation, the experiment was performed two times, one time with glucose ingestion and one time while fasting. UCP3 mRNA and UCP3 protein were determined by RT-competitive PCR and Western blot. In the fasted state, plasma FFA levels significantly increased ( P < 0.0001) during exercise (293 ± 25 vs. 1,050 ± 127 μmol/l), whereas they were unchanged after glucose ingestion (335 ± 54 vs. 392 ± 74 μmol/l). Also, fat oxidation was higher after fasting ( P < 0.05), whereas glucose oxidation was higher after glucose ingestion ( P< 0.05). In the fasted state, UCP3L mRNA expression was increased significantly ( P < 0.05) 4 h after exercise (4.6 ± 1.2 vs. 9.6 ± 3.3 amol/μg RNA). This increase in UCP3L mRNA expression was prevented by glucose ingestion. Acute exercise had no effect on UCP3 protein levels. In conclusion, we found that acute exercise had no direct effect on UCP3 mRNA expression. Abolishing the commonly observed increase in plasma FFA levels and/or fatty acid oxidation during and after exercise prevents the upregulation of UCP3 after acute exercise. Therefore, the previously observed increase in UCP3 expression appears to be an effect of prolonged elevation of plasma FFA levels and/or increased fatty acid oxidation.

scholarly journals Role of ketone signaling in the hepatic response to fasting

2019 ◽  
Vol 316 (5) ◽  
pp. G623-G631 ◽  
Author(s):  
Caroline E. Geisler ◽  
Susma Ghimire ◽  
Randy L. Bogan ◽  
Benjamin J. Renquist
Keyword(s):  
Fatty Acid ◽  
Mrna Expression ◽  
Fatty Acid Oxidation ◽  
Uncoupling Protein ◽  
Whole Body ◽  
Metabolic Adaptation ◽  
Acid Oxidation ◽  
Transcriptional Level ◽  
Nonalcoholic Fatty Liver ◽  
Fasting Response

Ketosis is a metabolic adaptation to fasting, nonalcoholic fatty liver disease (NAFLD), and prolonged exercise. β-OH butyrate acts as a transcriptional regulator and at G protein-coupled receptors to modulate cellular signaling pathways in a hormone-like manner. While physiological ketosis is often adaptive, chronic hyperketonemia may contribute to the metabolic dysfunction of NAFLD. To understand how β-OH butyrate signaling affects hepatic metabolism, we compared the hepatic fasting response in control and 3-hydroxy-3-methylglutaryl-CoA synthase II (HMGCS2) knockdown mice that are unable to elevate β-OH butyrate production. To establish that rescue of ketone metabolic/endocrine signaling would restore the normal hepatic fasting response, we gave intraperitoneal injections of β-OH butyrate (5.7 mmol/kg) to HMGCS2 knockdown and control mice every 2 h for the final 9 h of a 16-h fast. In hypoketonemic, HMGCS2 knockdown mice, fasting more robustly increased mRNA expression of uncoupling protein 2 (UCP2), a protein critical for supporting fatty acid oxidation and ketogenesis. In turn, exogenous β-OH butyrate administration to HMGCS2 knockdown mice decreased fasting UCP2 mRNA expression to that observed in control mice. Also supporting feedback at the transcriptional level, β-OH butyrate lowered the fasting-induced expression of HMGCS2 mRNA in control mice. β-OH butyrate also regulates the glycemic response to fasting. The fast-induced fall in serum glucose was absent in HMGCS2 knockdown mice but was restored by β-OH butyrate administration. These data propose that endogenous β-OH butyrate signaling transcriptionally regulates hepatic fatty acid oxidation and ketogenesis, while modulating glucose tolerance. NEW & NOTEWORTHY Ketogenesis regulates whole body glucose metabolism and β-OH butyrate produced by the liver feeds back to inhibit hepatic β-oxidation and ketogenesis during fasting.

Abstract 12117: The Cardioprotection of Trimetazidine Against Ischemic Injury is Mediated by AMPK and ERK Signaling Pathway

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Zhenling Liu ◽  
Yina Ma ◽  
Michelle Kuznicki ◽  
Xingchi Chen ◽  
Wanqing Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Ex Vivo ◽  
Ischemic Injury ◽  
Erk Signaling ◽  
Acid Oxidation ◽  
Ampk Signaling ◽  
Heart Perfusion

Introduction: Trimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. Hypothesis: AMP-activated protein kinase (AMPK) is an energy sensor that control ATP supply from substrate metabolism and protect heart from energy stress. TMZ changes the cardiac AMP/ATP ratio via modulating fatty acid oxidation, thereby it may trigger AMPK signaling cascade that contribute to protection heart from ischemia/reperfusion (I/R) injury. Methods: The mouse in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) were used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. Results: TMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p<0.05 vs. vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p<0.05). Intriguingly, the administration of ERK inhibitor, PD 98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Conclusions: Both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration.

Meal composition affects postprandial fatty acid oxidation

1993 ◽  
Vol 264 (6) ◽  
pp. R1065-R1070 ◽  
Author(s):  
D. M. Surina ◽  
W. Langhans ◽  
R. Pauli ◽  
C. Wenk
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Nutrient Utilization ◽  
Whole Body ◽  
Acid Oxidation ◽  
Plasma Ffa ◽  
Hepatic Fatty Acid Oxidation ◽  
Beta Hydroxybutyrate ◽  
Chain Fatty Acids

The influence of macronutrient content of a meal on postprandial fatty acid oxidation was investigated in 13 Caucasian males after consumption of a high-fat (HF) breakfast (33% carbohydrate, 52% fat, 15% protein) and after an equicaloric high-carbohydrate (HC) breakfast (78% carbohydrate, 6% fat, 15% protein). The HF breakfast contained short- and medium-chain fatty acids, as well as long-chain fatty acids. Respiratory quotient (RQ) and plasma beta-hydroxybutyrate (BHB) were measured during the 3 h after the meal as indicators of whole body substrate oxidation and hepatic fatty acid oxidation, respectively. Plasma levels of free fatty acids (FFA), triglycerides, glucose, insulin, and lactate were also determined because of their relationship to nutrient utilization. RQ was significantly lower and plasma BHB was higher after the HF breakfast than after the HC breakfast, implying that more fat is burned in general and specifically in the liver after an HF meal. As expected, plasma FFA and triglycerides were higher after the HF meal, and insulin and lactate were higher after the HC meal. In sum, oxidation of ingested fat occurred in response to a single HF meal.

scholarly journals Pancreatic Islet Adaptation to Fasting Is Dependent on Peroxisome Proliferator-Activated Receptor α Transcriptional Up-Regulation of Fatty Acid Oxidation

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 375-382 ◽  
Author(s):  
Sandrine Gremlich ◽  
Christopher Nolan ◽  
Raphaël Roduit ◽  
Rémy Burcelin ◽  
Marie-Line Peyot ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Pancreatic Islet ◽  
Cellular Response ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Hyperinsulinemic Hypoglycemia ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

The cellular response to fasting and starvation in tissues such as heart, skeletal muscle, and liver requires peroxisome proliferator-activated receptor-α (PPARα)-dependent up-regulation of energy metabolism toward fatty acid oxidation (FAO). PPARα null (PPARαKO) mice develop hyperinsulinemic hypoglycemia in the fasting state, and we previously showed that PPARα expression is increased in islets at low glucose. On this basis, we hypothesized that enhanced PPARα expression and FAO, via depletion of lipid-signaling molecule(s) for insulin exocytosis, are also involved in the normal adaptive response of the islet to fasting. Fasted PPARαKO mice compared with wild-type mice had supranormal ip glucose tolerance due to increased plasma insulin levels. Isolated islets from the PPARα null mice had a 44% reduction in FAO, normal glucose use and oxidation, and enhanced glucose-induced insulin secretion. In normal rats, fasting for 24 h increased islet PPARα, carnitine palmitoyltransferase 1, and uncoupling protein-2 mRNA expression by 60%, 62%, and 82%, respectively. The data are consistent with the view that PPARα, via transcriptionally up-regulating islet FAO, can reduce insulin secretion, and that this mechanism is involved in the normal physiological response of the pancreatic islet to fasting such that hypoglycemia is avoided.

scholarly journals Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart

2016 ◽  
Vol 311 (2) ◽  
pp. H347-H363 ◽  
Author(s):  
Arata Fukushima ◽  
Osama Abo Alrob ◽  
Liyan Zhang ◽  
Cory S. Wagg ◽  
Tariq Altamimi ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Energy Metabolism ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Acid Oxidation ◽  
Amino Acid Synthesis ◽  
Oxidation Rates ◽  
Cardiac Energy Metabolism ◽  
Cardiac Energy ◽  
The Impact

Dramatic maturational changes in cardiac energy metabolism occur in the newborn period, with a shift from glycolysis to fatty acid oxidation. Acetylation and succinylation of lysyl residues are novel posttranslational modifications involved in the control of cardiac energy metabolism. We investigated the impact of changes in protein acetylation/succinylation on the maturational changes in energy metabolism of 1-, 7-, and 21-day-old rabbit hearts. Cardiac fatty acid β-oxidation rates increased in 21-day vs. 1- and 7-day-old hearts, whereas glycolysis and glucose oxidation rates decreased in 21-day-old hearts. The fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD) and β-hydroxyacyl-CoA dehydrogenase (β-HAD), were hyperacetylated with maturation, positively correlated with their activities and fatty acid β-oxidation rates. This alteration was associated with increased expression of the mitochondrial acetyltransferase, general control of amino acid synthesis 5 like 1 (GCN5L1), since silencing GCN5L1 mRNA in H9c2 cells significantly reduced acetylation and activity of LCAD and β-HAD. An increase in mitochondrial ATP production rates with maturation was associated with the decreased acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α, a transcriptional regulator for mitochondrial biogenesis. In addition, hypoxia-inducible factor-1α, hexokinase, and phosphoglycerate mutase expression declined postbirth, whereas acetylation of these glycolytic enzymes increased. Phosphorylation rather than acetylation of pyruvate dehydrogenase (PDH) increased in 21-day-old hearts, accounting for the low glucose oxidation postbirth. A maturational increase was also observed in succinylation of PDH and LCAD. Collectively, our data are the first suggesting that acetylation and succinylation of the key metabolic enzymes in newborn hearts play a crucial role in cardiac energy metabolism with maturation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/acetylation-control-of-energy-metabolism-in-newborn-hearts/ .

Isoproterenol stimulates 5′-AMP-activated protein kinase and fatty acid oxidation in neonatal hearts

2010 ◽  
Vol 299 (4) ◽  
pp. H1135-H1145 ◽  
Author(s):  
Jagdip S. Jaswal ◽  
Chad R. Lund ◽  
Wendy Keung ◽  
Donna L. Beker ◽  
Ivan M. Rebeyka ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Oxidation ◽  
Energy Demand ◽  
Glucose Oxidation ◽  
Acid Oxidation ◽  
Acetyl Coa ◽  
Lactate Oxidation ◽  
Major Energy Source ◽  
Amp Activated Protein Kinase

Isoproterenol increases phosphorylation of LKB, 5′-AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC), enzymes involved in regulating fatty acid oxidation. However, inotropic stimulation selectively increases glucose oxidation in adult hearts. In the neonatal heart, fatty acid oxidation becomes a major energy source, while glucose oxidation remains low. This study tested the hypothesis that increased energy demand imposed by isoproterenol originates from fatty acid oxidation, secondary to increased LKB, AMPK, and ACC phosphorylation. Isolated working hearts from 7-day-old rabbits were perfused with Krebs solution (0.4 mM palmitate, 11 mM glucose, 0.5 mM lactate, and 100 mU/l insulin) with or without isoproterenol (300 nM). Isoproterenol increased myocardial O2 consumption (in J·g dry wt−1·min−1; 11.0 ± 1.4, n = 8 vs. 7.5 ± 0.8, n = 6, P < 0.05), and the phosphorylation of LKB (in arbitrary density units; 0.87 ± 0.09, n = 6 vs. 0.59 ± 0.08, n = 6, P < 0.05), AMPK (0.82 ± 0.08, n = 6 vs. 0.51 ± 0.06, n = 6, P < 0.05), and ACC-β (1.47 ± 0.14, n = 6 vs. 0.97 ± 0.07, n = 6, P < 0.05), with a concomitant decrease in malonyl-CoA levels (in nmol/g dry wt; 0.9 ± 0.9, n = 8 vs. 7.5 ± 1.3, n = 8, P < 0.05) and increase in palmitate oxidation (in nmol·g dry wt−1·min−1; 272 ± 45, n = 8 vs. 114 ± 9, n = 6, P < 0.05). Glucose and lactate oxidation were increased (in nmol·g dry wt−1·min−1; 253 ± 75, n = 8 vs. 63 ± 15, n = 9, P < 0.05 and 246 ± 43, n = 8 vs. 82 ± 11, n = 6, P < 0.05, respectively), independent of alterations in pyruvate dehydrogenase phosphorylation, but occurred secondary to a decrease in acetyl-CoA content and acetyl-CoA-to-free CoA ratio. As acetyl-CoA levels decrease in response to isoproterenol, despite an acceleration of the rates of palmitate and carbohydrate oxidation, these data suggest net rates of acetyl-CoA utilization exceed the net rates of acetyl-CoA generation.

Abstract 653: Muscle Ring Finger-1 (MuRF1) Expression Shifts Cardiomyocyte Substrate Utilization from Fatty Acids to Glucose

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Monte S Willis ◽  
Jon Schisler ◽  
Holly McDonough ◽  
Cam Patterson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Relative Proportion ◽  
Substrate Utilization ◽  
Acid Oxidation ◽  
Protective Mechanism ◽  
Dependent Manner ◽  
Dose Dependent

Previous work has suggested that MuRF1, a cardiac-specific protein, regulates metabolism by its interactions with proteins that regulate ATP transport, glycolysis, and the electron transport chain. We recently identified that MuRF1 is cardioprotective in ischemia reperfusion injury. In the current study, we investigated the effects of MuRF1 expression on metabolic substrate utilization and found that MuRF1 shifts substrate utilization from fatty acids to glucose in a dose-dependent manner. Isolated neonatal ventricular cardiomyocytes were treated with an adenovirus expressing MuRF1 (Ad.MuRF1) or GFP (Ad.GFP) at a range of 0–25 MOI (Multiplicity Of Infection). 14C-Oleate or 14C-glucose were added to cells for 1 hour and 14C-CO2 release was determined using the CO2-trapping method. Trapped 14CO2 and acid soluble metabolites were used to calculate total fatty acid oxidation. Cardiomyocytes treated with 5–25 MOI Ad.MuRF1 demonstrated a dose dependent decrease in fatty acid oxidation of 10.5 +/− 2.3(5 MOI), 8.5 +/− 1.9 (10 MOI), 6.6 +/− 1.6 (15 MOI), and 5.1 +/− 1.3 (25 MOI) nmol oleate/mg protein/h. Compared with control cardiomyocytes treated with 5–25 MOI Ad.GFP (average of 5–25 MOI=13.5 +/− 0.7 nmol oleate/mg protein/h), this represents a 22.2%– 62.2% decrease in fatty acid oxidation. Inversely, glucose oxidation increased with increasing MuRF1 expression. Cardiomyocytes infected with 25 MOI Ad.MuRF1 oxidized 184% more glucose (28.9 +/− 4.6 nmol glucose/mg protein/h) compared to control cells treated with 25 MOI Ad.GFP (15.7 +/− 1.3 nmol glucose/mg protein/h). Increasing MuRF1 expression resulted in no net gain or loss of calculated ATP production (1699 +/− 157 vs. 1480 +/− 188 nmol ATP/mg protein/h). The co-utilization of glucose and fatty acids as substrates for the production of ATP allows the heart to adapt to both environmental stress and disease. Increasing the relative proportion of glucose oxidation in relationship to fatty acids is a known protective mechanism during cardiac stress, and may represent one mechanism by which MuRF1 is cardioprotective.

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