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.

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.

scholarly journals Increased Fatty Acid Uptake and Altered Fatty Acid Metabolism in Insulin-Resistant Muscle of Obese Zucker Rats

Diabetes ◽  
2001 ◽  
Vol 50 (6) ◽  
pp. 1389-1396 ◽  
Author(s):  
Lorraine Patricia Turcotte ◽  
Jason Richard Swenberger ◽  
Michelle Zavitz Tucker ◽  
Alice Jane Yee
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Fatty Acid Uptake ◽  
Zucker Rats ◽  
Acid Uptake ◽  
Insulin Resistant ◽  
Obese Zucker Rats

An explanation for decreased ketogenesis in the liver of the obese Zucker rat

1989 ◽  
Vol 257 (4) ◽  
pp. R822-R828 ◽  
Author(s):  
M. J. Azain ◽  
J. A. Ontko
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Rat Liver ◽  
Intact Cell ◽  
Zucker Rats ◽  
Acid Oxidation ◽  
Palmitate Oxidation ◽  
Malonyl Coa ◽  
Obese Zucker Rats ◽  
Rat Livers

These studies were undertaken to further characterize and explain the differences in hepatic fatty acid metabolism between lean and obese Zucker rats. It was shown that the rate of palmitate or octanoate oxidation and the inhibition of palmitate oxidation by malonyl CoA in mitochondria isolated from lean and obese Zucker rats were similar. Cytochrome oxidase activity was similar in lean and obese rat livers. It was found that the addition of cytosol from the obese rat liver inhibited palmitate oxidation by 20-30% in mitochondria isolated from lean or obese rat livers and thus reproduced the conditions observed in the intact cell. Increased concentrations of metabolites such as malonyl CoA and glycerophosphate in the liver of the obese rat are likely contributors to this inhibitory effect. These results are extrapolated to the intact cell and suggest that decreased hepatic fatty acid oxidation in the obese rat can be accounted for by cytosolic influences on the mitochondria. The decreased rate of fatty acid oxidation observed in the intact hepatocyte or perfused liver cannot be explained by a defect in the capacity of mitochondria to oxidize substrate or by a decrease in mitochondrial number in the obese rat liver.

In obese rat muscle transport of palmitate is increased and is channeled to triacylglycerol storage despite an increase in mitochondrial palmitate oxidation

2009 ◽  
Vol 296 (4) ◽  
pp. E738-E747 ◽  
Author(s):  
Graham P. Holloway ◽  
Carley R. Benton ◽  
Kerry L. Mullen ◽  
Yuko Yoshida ◽  
Laelie A. Snook ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Zucker Rats ◽  
Acid Oxidation ◽  
Fatty Acid Transport ◽  
Acid Transport ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Palmitate Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Obese Zucker Rats

Intramuscular triacylglycerol (IMTG) accumulation in obesity has been attributed to increased fatty acid transport and/or to alterations in mitochondrial fatty acid oxidation. Alternatively, an imbalance in these two processes may channel fatty acids into storage. Therefore, in red and white muscles of lean and obese Zucker rats, we examined whether the increase in IMTG accumulation was attributable to an increased rate of fatty acid transport rather than alterations in subsarcolemmal (SS) or intermyofibrillar (IMF) mitochondrial fatty acid oxidation. In obese animals selected parameters were upregulated, including palmitate transport (red: +100%; white: +51%), plasmalemmal FAT/CD36 (red: +116%; white: +115%; not plasmalemmal FABPpm, FATP1, or FATP4), IMTG concentrations (red: ∼2-fold; white: ∼4-fold), and mitochondrial content (red +30%). Selected mitochondrial parameters were also greater in obese animals, namely, palmitate oxidation (SS red: +91%; SS white: +26%; not IMF mitochondria), FAT/CD36 (SS: +65%; IMF: +65%), citrate synthase (SS: +19%), and β-hydroxyacyl-CoA dehydrogenase activities (SS: +20%); carnitine palmitoyltransferase-I activity did not differ. A comparison of lean and obese rat muscles revealed that the rate of change in IMTG concentration was eightfold greater than that of fatty acid oxidation (SS mitochondria), when both parameters were expressed relative to fatty transport. Thus fatty acid transport, esterification, and oxidation (SS mitochondria) are upregulated in muscles of obese Zucker rats, with these effects being most pronounced in red muscle. The additional fatty acid taken up is channeled primarily to esterification, suggesting that upregulation in fatty acid transport as opposed to altered fatty acid oxidation is the major determinant of intramuscular lipid accumulation.

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.

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.

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.

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