scholarly journals Cardarine (GW501516) Effects on Improving Metabolic Syndrome

2021 ◽  
Vol 2 (2) ◽  
pp. 22-27
Author(s):  
Jeremy Park ◽  
Joon Young Kim
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Adverse Effects ◽  
Fatty Acid Oxidation ◽  
Real Life ◽  
Tolerance Test ◽  
Acid Oxidation ◽  
Skeletal Muscle Biopsy ◽  
Multiple Metabolic Syndrome

The present study hypothesized that treatment with GW501516 (a selective PPAR-δ agonist) lowers lipids by increasing fatty acid oxidation without adverse effects on oxidative stress. Caucasian men (age 18-50 years, n=18) were randomly assigned to treatment with GW501516, GW590735, or placebo for two weeks while residing in a clinical research facility. A meal tolerance test, skeletal muscle biopsy, and blood/breath sampling were conducted. The study reported that treatment with GW501516 ameliorated multiple metabolic abnormalities associated with metabolic syndrome including oxidative stress, obesity, dyslipidemia, and insulin resistance, all while increasing fatty acid oxidation. Notably, no adverse effects were reported. However, the restricted living conditions and/or diets that the participants were subjected to likely do not resemble their normal lifestyle. Therefore, the beneficial effects of GW501516 on metabolic health observed in the study should further be investigated in a real-life setting. During participant recruitment, the use of dietary supplements were minimally considered, thereby increasing the risk for confounding effects on the metabolic parameters assessed in the study. Also, recruiting a larger and more diverse population would allow for a more detailed analysis that may benefit a broader range of people (i.e., examining the effects of GW501516 in certain ethnic groups or with/without exercise programs). Additional research on GW501516 and other PPAR-δ agonists is encouraged since it appears that this class of drugs can ameliorate multiple metabolic syndrome features. Future studies should consider additional metrics relevant to metabolic syndrome such as C-reactive protein, cortisol, and homocysteine.

scholarly journals 472: Oxidative stress impairs fatty acid oxidation in the human term placenta

2017 ◽  
Vol 216 (1) ◽  
pp. S279
Author(s):  
Megan M. Thomas ◽  
Maricela Haghiac ◽  
Judi Minium ◽  
Virtu Calabuig-Navarro ◽  
Perrie O'Tierney-Ginn
Keyword(s):  
Oxidative Stress ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Human Term Placenta ◽  
Term Placenta

Abstract 169: miR-21-5p Regulation of Lipid Content and Peroxidation in H9C2 Cells

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sandra Chuppa ◽  
Alison J Kriegel
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Content ◽  
Untreated Control ◽  
Left Ventricular ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
H9c2 Cells

Cardiovascular pathologies are the leading single cause of death in chronic kidney disease (CKD) patients. We have found that the 5/6 nephrectomy model of CKD leads to an upregulation of miR-21-5p in the left ventricle 7 weeks after surgery, targeting peroxisome proliferator-activated receptor alpha (PPARα). PPARα is a regulator of fatty acid uptake and metabolism. In our model we find that suppression of miR-21-5p alters the expression of numerous genes involved with fatty acid oxidation and glycolysis, presumably through its regulatory action on PPARα and/or additional targets. We also find that 5/6Nx rats exhibit dyslipidemia and increased left ventricular lipid content at this time. In this study we evaluated the potential for knockdown or overexpression of miR-21-5p to regulate lipid content and peroxidation in H9C2 cells. Cells were transfected with anti-miR-21-5p (40nM), pre-miR-21-5p (20nM) or appropriate scrambled oligonucleotide controls. After 24 hours medium was changed and half of the cells from each transfection group were treated with lipid (0.66 mM oleic acid and 0.33 mM palmitic acid) for 48 hours (n=6/treatment group for each set of experiments). Lipid content, measured by AdipoRed assay (Lonza) was significantly increased with lipid treatment (nearly two-fold). Overexpression of miR-21-5p significantly attenuated this increase (228.0 ± 9.7 vs. 198.2 ± 8.9% of untreated control), while suppression of miR-21-5p augmented lipid content (235.8 ± 11.2 vs. 328.1 ± 12.3% of untreated control). These results were supported by imaging of Oil Red O stained cells. We found that the abundance of malondialdehyde (MDA), a product of lipid peroxidation, was significantly increased in response to lipid treatment. Overexpression of miR-21-5p reduced MDA content in untreated and lipid treated cells, suggesting that miR-21-5p reduces oxidative stress. Suppression of miR-21-5p had no effect on MDA levels. These results indicate that overexpression of miR-21-5p attenuates both lipid content and lipid peroxidation in H9C2 cells. Ongoing studies aimed at evaluation of alterations in fatty acid oxidation and oxidative stress will further aid in determining the functional impact of miR-21-5p on associated pathways in cardiac tissue.

Alterations in plasma and tissue lipids associated with obesity and metabolic syndrome

2008 ◽  
Vol 114 (3) ◽  
pp. 183-193 ◽  
Author(s):  
Concepción M. Aguilera ◽  
Mercedes Gil-Campos ◽  
Ramón Cañete ◽  
Ángel Gil
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Oxidation ◽  
Plasma Lipids ◽  
Density Lipoprotein ◽  
Cellular Fatty Acid ◽  
Acid Oxidation ◽  
Subsequent Increase ◽  
Peripheral Tissues

The MS (metabolic syndrome) is a cluster of clinical and biochemical abnormalities characterized by central obesity, dyslipidaemia [hypertriglyceridaemia and decreased HDL-C (high-density lipoprotein cholesterol)], glucose intolerance and hypertension. Insulin resistance, hyperleptinaemia and low plasma levels of adiponectin are also widely related to features of the MS. This review focuses on lipid metabolism alterations associated with the MS, paying special attention to changes in plasma lipids and cellular fatty acid oxidation. Lipid metabolism alterations in liver and peripheral tissues are addressed, with particular reference to adipose and muscle tissues, and the mechanisms by which some adipokines, namely leptin and adiponectin, mediate the regulation of fatty acid oxidation in those tissues. Activation of the AMPK (AMP-dependent kinase) pathway, together with a subsequent increase in fatty acid oxidation, appear to constitute the main mechanism of action of these hormones in the regulation of lipid metabolism. Decreased activation of AMPK appears to have a role in the development of features of the MS. In addition, alteration of AMPK signalling in the hypothalamus, which may function as a sensor of nutrient availability, integrating multiple nutritional and hormonal signals, may have a key role in the appearance of the MS.

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