Trans Fatty Acid Intake Modulates the Expression of Uncoupling Proteins 2 and 3 (UCP2 & UCP3) mRNA in Children

Increased consumption of Trans Fats is associated with increased risk of Coronary Heart Disease. Uncoupling proteins (UCPs) are mitochondrial proteins that disperse the inter-membrane electrochemical potential as heat. We aimed to detect the relation of high Trans-fat intake in diet on the expression of UCP2&3 m-RNA in children. A specific questionnaire to parents of sixty-eight children (4-15 years) was conducted. Accordingly, the subjects were sub-grouped into; High Trans-fat consuming group (37 subjects) and a Medium Trans-fat consuming one (31 subjects). Samples collected from Peripheral blood to analyze UCP2&3 mRNA expression by Real Time Polymerase Chain Reaction (RT-PCR). Levels of UCP2 expression was reduced in children consuming High Trans-fat (2.5 ±0.7) in comparison with Medium Trans-fat consuming ones (1.5± 0.2) with (p<0.001). However, not much significance was showed in UCP3 expression with values (2.1±0.5) in the High consuming group and (1.9±0.2) in Medium consuming group with (p=0.08). In Delta relationship the diet-induced changes in UCP2 (r=0.66, P=0.002) and UCP3 (r=0.61, P=0.06) mRNA expression was negatively correlated with percentage of Trans-fat in diet. The correlation of UCP2&3 mRNA expression and high Trans-fat intake suggests a mechanism by which high Trans-fat diet plays a role in childhood obesity.

Effect of Ligustrazine on Myocardial Ischemia/reperfusion Injury Through Upregulating UCP3

Background: The study aimed to investigate whether ligustrazine, a traditional Chinese medicine, could attenuate myocardial ischemia/reperfusion (I/R) injury and explore the potential mechanism.Methods: 32 Sprague-Dawley rats were divided equally into four groups: sham operation (S); (I/R); I/R + ligustrazine preconditioning (Lig); I/R + ligustrazine preconditioning + mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) (Lig + LND). Myocardial I/R model was established and ligustrazine was administered intraperitoneally 5 min prior to ischemia, LND was administered intraperitoneally 10 min prior to reperfusion. The infarct area (IA) was measured by Evans blue staining, where levels of Myocardial injury markers, malondialdehyde (MDA), superoxide dismutase (SOD), adenosine triphosphate (ATP) were detected. RT-PCR and Western Blot were adopted to measure the uncoupling protein 3 (UCP3) expression.Results: Compared to I/R group, the IA/area at risk (AAR) in Lig, and Lig + LND groups were significantly decreased, UCP3 levels of mRNA and protein were increased (P < 0.05). Compared to Lig group, the IA/AAR in Lig + LND group was significantly increased (P < 0.05). Ligustrazine pretreatment increased SOD, ATP activity, and decreased cardiac troponin I (cTnI), creatine kinase-muscle/brain (CK-MB), lactate dehydrogenase (LDH) and MDA activities. The effect of ligustrazine was reversed by LND.Conclusion: The present results indicated that ischemic preconditioning of ligustrazine might protect myocardium against I/R injury through upregulating UCP3 expression.

Protective Effect of Peroxisome Proliferator-Activated ReceptorαActivation against Cardiac Ischemia-Reperfusion Injury Is Related to Upregulation of Uncoupling Protein-3

Activation of peroxisome proliferator-activated receptorα(PPARα) confers cardioprotection, while its mechanism remains elusive. We investigated the protective effect of PPARαactivation against cardiac ischemia-reperfusion injury in terms of the expression of uncoupling protein (UCP). Myocardial infarct size and UCP expression were measured in rats treated with WY-14643 20 mg/kg, a PPARαligand, or vehicle. WY-14643 increased UCP3 expressionin vivo. Myocardial infarct size was decreased in the WY-14643 group (76 ± 8% versus 42 ± 12%,P<0.05). During reperfusion, the incidence of arrhythmia was higher in the control group compared with the WY-14643 group (9/10 versus 3/10,P<0.05). H9c2 cells were incubated for 24 h with WY-14643 or vehicle. WY-14643 increased UCP3 expression in H9c2 cells. WY-14643 decreased hypoxia-stimulated ROS production. Cells treated with WY-14643 were more resistant to hypoxia-reoxygenation than the untreated cells. Knocking-down UCP3 by siRNA prevented WY-14643 from attenuating the production of ROS. UCP3 siRNA abolished the effect of WY-14643 on cell viability against hypoxia-reoxygenation. In summary, administration of PPARαagonist WY-14643 mitigated the extent of myocardial infarction and incidence of reperfusion-induced arrhythmia. PPARαactivation conferred cytoprotective effect against hypoxia-reoxygenation. Associated mechanisms involved increased UCP3 expression and resultant attenuation of ROS production.