Increased nonoxidative glycolysis despite continued fatty acid uptake during demand-induced myocardial ischemia

2002 ◽  
Vol 282 (5) ◽  
pp. H1871-H1878 ◽  
Author(s):  
Margaret P. Chandler ◽  
Hazel Huang ◽  
Tracy A. McElfresh ◽  
William C. Stanley
Keyword(s):  
Fatty Acid ◽  
Coronary Artery ◽  
Fatty Acid Oxidation ◽  
Lactate Production ◽  
Fatty Acid Uptake ◽  
Anterior Wall ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Substrate Uptake ◽  
Exogenous Fatty Acid

During stress, patients with coronary artery disease frequently fail to increase coronary flow and myocardial oxygen consumption (MV˙o 2) in response to a greater demand for oxygen, resulting in “demand-induced” ischemia. We tested the hypothesis that dobutamine infusion with flow restriction stimulates nonoxidative glycolysis without a change in MV˙o 2 or fatty acid uptake. Measurements were made in the anterior wall of anesthetized open-chest swine hearts ( n = 7). The left anterior descending (LAD) coronary artery flow was controlled via an extracorporeal perfusion circuit, and substrate uptake and oxidation were measured with radiotracers. Demand-induced ischemia was produced with intravenous dobutamine (15 μg · kg−1 · min−1) and 20% reduction in LAD flow for 20 min. Despite no change in MV˙o 2, there was a switch from lactate uptake (5.9 ± 3.1) to production (74.5 ± 16.3 μmol/min), glycogen depletion (66%), and increased glucose uptake (105%), but no change in anterior wall power or the index of anterior wall energy efficiency. There was no change in the rate of tracer-measured fatty acid uptake; however, exogenous fatty acid oxidation decreased by 71%. Thus demand-induced ischemia stimulated nonoxidative glycolysis and lactate production, but did not effect fatty acid uptake despite a fall in exogenous fatty acid oxidation.

Theobromine ameliorates nonalcoholic fatty liver disease by regulating hepatic lipid metabolism via mTOR signaling pathway in vivo and in vitro

2020 ◽  
Author(s):  
Dan Wei ◽  
Shaofei Wu ◽  
Jie Liu ◽  
Xiaoqian Zhang ◽  
Xiaoling Guan ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Signaling Pathway ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Uptake ◽  
Mtor Signaling ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Mtor Signaling Pathway

Theobromine, a methylxanthine present in cocoa, has been shown to possess many beneficial pharmacological properties such as anti-oxidative stress, anti-inflammatory property, and anti-microbial activity. In this study, we investigated the effects of theobromine on NAFLD and the possible underlying mechanisms in vivo and in vitro. The results showed that theobromine reduced body weight, fat mass and improved dyslipidemia. Theobromine decreased liver weight, mitigated liver injury, and significantly reduced hepatic TG level in mice with obesity. Histological examinations also showed hepatic steatosis was alleviated after theobromine treatment. Furthermore, theobromine reversed the elevated mRNA and protein expression of SREBP-1c, FASN, CD36, FABP4 and the suppressed expression of PPARα, CPT1a in the liver of mice with obesity, which were responsible for lipogenesis, fatty acid uptake and fatty acid oxidation respectively. In vitro, theobromine also downregulated SREBP-1c, FASN, CD36, FABP4 and upregulated PPARα, CPT1a mRNA and protein levels in hepatocytes in a dose-dependent manner, while these changes were reversed by L-Leucine, an mTOR agonist. The present study demonstrated that theobromine improved NAFLD by inhibiting lipogenesis, fatty acid uptake and promoting fatty acid oxidation in the liver and hepatocytes, which might be associated with its suppression of mTOR signaling pathway.

Effect of hyperglycemia-hyperinsulinemia on whole body and regional fatty acid metabolism

1999 ◽  
Vol 276 (3) ◽  
pp. E427-E434 ◽  
Author(s):  
Labros S. Sidossis ◽  
Bettina Mittendorfer ◽  
David Chinkes ◽  
Eric Walser ◽  
Robert R. Wolfe
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Fatty Acid Uptake ◽  
Whole Body ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Similar Extent ◽  
Body Level

The effects of combined hyperglycemia-hyperinsulinemia on whole body, splanchnic, and leg fatty acid metabolism were determined in five volunteers. Catheters were placed in a femoral artery and vein and a hepatic vein. U-13C-labeled fatty acids were infused, once in the basal state and, on a different occasion, during infusion of dextrose (clamp; arterial glucose 8.8 ± 0.5 mmol/l). Lipids and heparin were infused together with the dextrose to maintain plasma fatty acid concentrations at basal levels. Fatty acid availability in plasma and fatty acid uptake across the splanchnic region and the leg were similar during the basal and clamp experiments. Dextrose infusion decreased fatty acid oxidation by 51.8% (whole body), 47.4% (splanchnic), and 64.3% (leg). Similarly, the percent fatty acid uptake oxidized decreased at the whole body level (53 to 29%), across the splanchnic region (30 to 13%), and in the leg (48 to 22%) during the clamp. We conclude that, in healthy men, combined hyperglycemia-hyperinsulinemia inhibits fatty acid oxidation to a similar extent at the whole body level, across the leg, and across the splanchnic region, even when fatty acid availability is constant.

Hyperglycemia-induced inhibition of splanchnic fatty acid oxidation increases hepatic triacylglycerol secretion

1998 ◽  
Vol 275 (5) ◽  
pp. E798-E805 ◽  
Author(s):  
Labros S. Sidossis ◽  
Bettina Mittendorfer ◽  
Eric Walser ◽  
David Chinkes ◽  
Robert R. Wolfe
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Fatty Acid Uptake ◽  
Secretion Rate ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Hepatic Triacylglycerol

The effect of hyperglycemia (∼8 mmol/l) on splanchnic fatty acid oxidation and triacylglycerol (TG) secretion rates was investigated in five healthy men. U-13C-labeled fatty acids were infused to estimate fatty acid kinetics and oxidation across the splanchnic region, and in vivo labeled very low density lipoprotein (VLDL)-TG was infused to estimate TG secretion rate. Plasma fatty acid carbon enrichment and concentration were maintained constant by infusion of lipids and heparin in the hyperglycemia experiments. Fatty acid uptake by the splanchnic region was 1.4 ± 0.2 and 2.2 ± 0.9 μmol ⋅ kg−1⋅ min−1in the basal and clamp experiments, respectively, whereas fatty acid oxidation decreased from 0.4 ± 0.04 to 0.2 ± 0.05 μmol ⋅ kg−1⋅ min−1( P < 0.05). Hepatic TG secretion increased from 0.35 ± 0.07 μmol ⋅ kg−1⋅ min−1in the basal state to 0.53 ± 0.11 μmol ⋅ kg−1⋅ min−1after 15 h of hyperglycemia ( P< 0.05). Similarly, plasma VLDL-TG concentration increased from 0.28 ± 0.06 to 0.43 ± 0.05 mmol/l during the clamp ( P < 0.05). In summary, hyperglycemia attenuates fatty acid oxidation in the splanchnic region in human volunteers, even when fatty acid availability is constant. This adaptation results in a significant increase in the VLDL-TG secretion rate and concentration in plasma.

Meal fatty acid uptake in human adipose tissue: technical and experimental design issues

2000 ◽  
Vol 279 (2) ◽  
pp. E447-E454 ◽  
Author(s):  
S. A. Romanski ◽  
Rita M. Nelson ◽  
Michael D. Jensen
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Experimental Design ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Uptake ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Tissue Uptake ◽  
Design Issues ◽  
Isotopic Tracers

The adipose tissue uptake of dietary fat has been studied using fatty acid radiotracers incorporated into a meal, followed by adipose tissue biopsies. A number of experimental design issues, including the use of isotopic tracers to measure meal fatty acid oxidation and plasma appearance of tracer, as well as the heterogeneity of adipose tissue fatty acid uptake, have been addressed. We examined these questions in a study of 24 volunteers (12 men and 12 women) who consumed a meal containing [3H]triolein and [14C]triolein. Slight differences in the purity of [3H]triolein vs. [14C]triolein were found, which could affect the apparent adipose tissue uptake of meal fatty acids. The adipose tissue triglyceride specific activity from bilateral biopsy sites agreed well, implying that a unilateral biopsy is satisfactory for measuring tracer uptake. Meal fatty acid oxidation measured using [3H]triolein and [14C]triolein was well correlated ( r = 0.79, P < 0.0001). The peak tracer appearance in plasma chylomicrons occurred 1 h after the ingestion of a second, unlabeled meal. Our findings have implications for the experimental design of future meal fatty acid tracer/adipose tissue biopsy studies.

Characterization of cardiac malonyl-CoA decarboxylase and its putative role in regulating fatty acid oxidation

1998 ◽  
Vol 275 (6) ◽  
pp. H2122-H2129 ◽  
Author(s):  
Jason R. B. Dyck ◽  
Amy J. Barr ◽  
Rick L. Barr ◽  
Pappachan E. Kolattukudy ◽  
Gary D. Lopaschuk
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Uptake ◽  
Partial Purification ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Adult Rats ◽  
Adult Rat ◽  
Oxidation Rates ◽  
Malonyl Coa

Malonyl-CoA is a potent inhibitor of fatty acid uptake into the mitochondria. Although the synthesis of malonyl-CoA in the heart by acetyl-CoA carboxylase (ACC) has been well characterized, no information is available as to how malonyl-CoA is degraded. We demonstrate that malonyl-CoA decarboxylase (MCD) activity is present in the heart. Partial purification revealed a protein of ∼50 kDa. The role of MCD in regulating fatty acid oxidation was also studied using isolated, perfused hearts from newborn rabbits and adult rats. Fatty acid oxidation in rabbit hearts increased dramatically between 1 day and 7 days after birth, which was accompanied by a decrease in both ACC activity and malonyl-CoA levels and a parallel increase in MCD activity. When adult rat hearts were aerobically reperfused after a 30-min period of no-flow ischemia, levels of malonyl-CoA decreased dramatically, which was accompanied by a decrease in ACC activity, a maintained MCD activity, and an increase in fatty acid oxidation rates. Taken together, our data suggest that the heart has an active MCD that has an important role in regulating fatty acid oxidation rates.

Metabolic challenges reveal impaired fatty acid metabolism and translocation of FAT/CD36 but not FABPpm in obese Zucker rat muscle

2007 ◽  
Vol 293 (2) ◽  
pp. E566-E575 ◽  
Author(s):  
Xiao-Xia Han ◽  
Adrian Chabowski ◽  
Narendra N. Tandon ◽  
Jorge Calles-Escandon ◽  
Jan F. C. Glatz ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Metabolism ◽  
Fatty Acid Uptake ◽  
Zucker Rats ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Rat Muscle ◽  
Fatty Acid Transporter ◽  
Obese Zucker Rats

We examined, in muscle of lean and obese Zucker rats, basal, insulin-induced, and contraction-induced fatty acid transporter translocation and fatty acid uptake, esterification, and oxidation. In lean rats, insulin and contraction induced the translocation of the fatty acid transporter FAT/CD36 (43 and 41%, respectively) and plasma membrane-associated fatty acid binding protein (FABPpm; 19 and 60%) and increased fatty acid uptake (63 and 40%, respectively). Insulin and contraction increased lean muscle palmitate esterification and oxidation 72 and 61%, respectively. In obese rat muscle, basal levels of sarcolemmal FAT/CD36 (+33%) and FABPpm (+14%) and fatty acid uptake (+30%) and esterification (+32%) were increased, whereas fatty acid oxidation was reduced (−28%). Insulin stimulation of obese rat muscle increased plasmalemmal FABPpm (+15%) but not plasmalemmal FAT/CD36, blunted fatty acid uptake and esterification, and failed to reduce fatty acid oxidation. In contracting obese rat muscle, the increases in fatty acid uptake and esterification and FABPpm translocation were normal, but FAT/CD36 translocation was impaired and fatty acid oxidation was blunted. There was no relationship between plasmalemmal fatty acid transporters and palmitate partitioning. In conclusion, fatty acid metabolism is impaired at several levels in muscles of obese Zucker rats; specifically, they are 1) insulin resistant with respect to FAT/CD36 translocation and fatty acid uptake, esterification, and oxidation and 2) contraction resistant with respect to fatty acid oxidation and FAT/CD36 translocation, but, conversely, 3) obese muscles are neither insulin nor contraction resistant at the level of FABPpm. Finally, 4) there is no evidence that plasmalemmal fatty acid transporters contribute to the channeling of fatty acids to specific metabolic destinations within the muscle.

scholarly journals An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart

2010 ◽  
Vol 299 (5) ◽  
pp. E721-E729 ◽  
Author(s):  
Xiangping Fang ◽  
Rengasamy Palanivel ◽  
Justin Cresser ◽  
Kristin Schram ◽  
Riya Ganguly ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Uptake ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Perfused Heart ◽  
Ampk Signaling ◽  
Akt Phosphorylation ◽  
Neonatal Cardiomyocytes

Adiponectin promotes cardioprotection by various mechanisms, and this study used primary cardiomyocytes and the isolated working perfused heart to investigate cardiometabolic effects. We show in adult cardiomyocytes that adiponectin increased CD36 translocation and fatty acid uptake as well as insulin-stimulated glucose transport and Akt phosphorylation. Coimmunoprecipitation showed that adiponectin enhanced association of AdipoR1 with APPL1, subsequent binding of APPL1 with AMPKα2, which led to phosphorylation and inhibition of ACC and increased fatty acid oxidation. Using siRNA to effectively knockdown APPL1 in neonatal cardiomyocytes, we demonstrated an essential role for APPL1 in mediating increased fatty acid uptake and oxidation by adiponectin. Importantly, enhanced fatty acid oxidation in conjunction with AMPK and ACC phosphorylation was also observed in the isolated working heart. Despite increasing fatty acid oxidation and myocardial oxygen consumption, adiponectin increased hydraulic work and maintained cardiac efficiency. In summary, the present study documents several beneficial metabolic effects mediated by adiponectin in the heart and provides novel insight into the mechanisms behind these effects, in particular the importance of APPL1.

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