scholarly journals Inhibition of Fatty Acid Metabolism Increases EPA and DHA Levels and Protects against Myocardial Ischaemia-Reperfusion Injury in Zucker Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Janis Kuka ◽  
Marina Makrecka-Kuka ◽  
Karlis Vilks ◽  
Stanislava Korzh ◽  
Helena Cirule ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Plasma Insulin ◽  
Myocardial Infarct ◽  
Zucker Rats ◽  
Acid Oxidation ◽  
Myocardial Infarct Size ◽  
Metabolome Analysis ◽  
Plasma Insulin Concentration ◽  
Fatty Acid Utilization ◽  
Long Chain

Long-chain ω-3 polyunsaturated fatty acids (PUFAs) are known to induce cardiometabolic benefits, but the metabolic pathways of their biosynthesis ensuring sufficient bioavailability require further investigation. Here, we show that a pharmacological decrease in overall fatty acid utilization promotes an increase in the levels of PUFAs and attenuates cardiometabolic disturbances in a Zucker rat metabolic syndrome model. Metabolome analysis showed that inhibition of fatty acid utilization by methyl-GBB increased the concentration of PUFAs but not the total fatty acid levels in plasma. Insulin sensitivity was improved, and the plasma insulin concentration was decreased. Overall, pharmacological modulation of fatty acid handling preserved cardiac glucose and pyruvate oxidation, protected mitochondrial functionality by decreasing long-chain acylcarnitine levels, and decreased myocardial infarct size twofold. Our work shows that partial pharmacological inhibition of fatty acid oxidation is a novel approach to selectively increase the levels of PUFAs and modulate lipid handling to prevent cardiometabolic disturbances.

scholarly journals 146 Nutritional Advances in Fetal and neonatal development: effect of fatty acid supplementation

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 121-122
Author(s):  
Alejandro E Relling
Keyword(s):  
Small Intestine ◽  
Fatty Acid ◽  
Plasma Insulin ◽  
Linear Increase ◽  
Late Gestation ◽  
Insulin Concentration ◽  
Plasma Insulin Concentration ◽  
Pufa Supplementation ◽  
Epa And Dha ◽  
Offspring Growth

Abstract Data from a series of experiments demonstrates that maternal supply of polyunsaturated fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), during late gestation affects offspring growth. The increase in growth is independent on the fatty acid supplemented during the growing or finishing phase of the offspring; but it is sex dependent. Dam PUFA supplementation increases wether growth. Supplementation with EPA and DHA to pregnant ewes and to their offspring after weaning showed a treatment interaction in mRNA concentration of hypothalamic neuropeptides associated with dry matter intake (DMI) regulation. A dose increased in EPA and DHA in pregnant ewe diets shows a linear increase in growth, but a quadratic change in DMI or feed efficiency; growth was associated with a linear increase in plasma glucose concentration and a linear decrease in plasma ghrelin concentration. In lambs born from ewes supplemented with different sources of FA during a glucose tolerance test; males’ plasma insulin concentration increased as FA unsaturation degree increased in the dam diet, the opposite happened with females’ plasma insulin concentration. Recent data from our lab showed that the supplementation with EPA and DHA during the last third of gestation to pregnant ewes increased liver and small intestine global DNA methylation and small intestine transporters for amino acids in the fetus. Despite EPA and DHA during late gestation increase growth in the offspring; when EPA and DHA were supplemented in early gestation, offspring growth was lesser that lambs born from ewes supplemented a saturated and monounsaturated lipid. The reason for the difference in results it is not clear. However, more studies focusing in some aspect of the biology will help to understand what specific fatty acid needs to be supplemented at different stages of gestation to improve offspring growth.

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.

scholarly journals Deletion of nuclear factor-κB p50 upregulates fatty acid utilization and contributes to an anti-obesity and high-endurance phenotype in mice

2015 ◽  
Vol 309 (6) ◽  
pp. E523-E533 ◽  
Author(s):  
Yoshihiko Minegishi ◽  
Satoshi Haramizu ◽  
Koichi Misawa ◽  
Akira Shimotoyodome ◽  
Tadashi Hase ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Nuclear Factor Κb ◽  
Whole Body ◽  
Acid Oxidation ◽  
Endurance Capacity ◽  
Peroxisome Proliferator ◽  
Primary Role ◽  
Nuclear Factor ◽  
Oxidation Activity ◽  
Fatty Acid Utilization

The transcription factor nuclear factor-κB (NF-κB) plays an important role in regulating physiological processes such as immunity and inflammation. In addition to this primary role, NF-κB interacts physically with peroxisome proliferator-activated receptors regulating lipid metabolism-related gene expression and inhibits their transcriptional activity. Therefore, inhibition of NF-κB may promote fatty acid utilization, which could ameliorate obesity and improve endurance capacity. To test this hypothesis, we attempted to elucidate the energy metabolic status of mice lacking the p50 subunit of NF-κB (p50 KO mice) from the tissue to whole body level. p50 KO mice showed a significantly lower respiratory quotient throughout the day than did wild-type (WT) mice; this decrease was associated with increased fatty acid oxidation activity in liver and gastrocnemius muscle of p50 KO mice. p50 KO mice that were fed a high-fat diet were also resistant to fat accumulation and adipose tissue inflammation. Furthermore, p50 KO mice showed a significantly longer maximum running time compared with WT mice, with a lower respiratory exchange ratio during exercise as well as higher residual muscle glycogen content and lower blood lactate levels after exercise. These results suggest that p50 deletion facilitates fatty acid catabolism, leading to an anti-obesity and high-endurance phenotype of mice and supporting the idea that NF-κB is an important regulator of energy metabolism.

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