The Value of Serum Uncoupling Protein-2 Level for the Patients With Sepsis.

BACKGROUND: To investigate the potential utility of serum uncoupling protein-2 (UCP2) level as a biomarker in septic patients. METHODS: Critically ill patients with diagnoses of sepsis-sepsis non-shock group (n = 20) and septic shock group (n = 53), and a control group (n = 15) were enrolled within 24 h of entry into the ICU. Serum levels of UCP2 were measured by enzyme-linked immunosorbent assay (ELISA) at ICU admission for all the groups and at ICU discharge for septic shock group. Clinical parameters and laboratorial tests (APACHE II, SOFA, lactate, etc.) were also collected. RESULTS: Serum UCP2 concentrations on ICU admission were significantly increased in septic shock group and sepsis non-shock group, compared with control subjects (263.21 ±â€Š29.99 vs. 115.96 ±â€Š32.99 vs. 60.56 ±â€Š10.05 pg/mL, P < 0.001). Concentrations of UCP2 performed better than other parameters (APACHE II score, SOFA score, procalcitonin, and WBC) in predicting the incidence of sepsis or septic shock on the day of ICU admission, as reflected by AUC. On the day of ICU admission, the AUC for UCP2 level associated with 28-day mortality was 0.704, higher than the AUC for SOFA and APACHE II scores. Patients with higher admission levels of UCP2 (>246.52 pg/mL) had significantly increased 28-day mortality compared with those with lower UCP2 levels (<246.52 pg/mL). CONCLUSION: Serum UCP2 levels at admission were markedly increased in patients with sepsis, which is useful for early diagnose and prognostic prediction. UCP2 is a potential biomarker for sepsis, or even a subtype of sepsis.

UCP2, SHBG, Leptin, and T3 Levels are Associated with Resting Energy Expenditure in Obese Women.

OBJECTIVE: The aim of this study was to investigate the association of Sex Hormone Binding Globulin (SHBG) with leptin, Triidothyronine (T3), and Uncoupling Protein 2 (UCP2) in obese women with low and normal Resting Energy Expenditure (REE) and to determine the role of these factors in the regulation of REE in obese women. METHOD: A total 49 subjects (25-50 years old) were selected. Anthropometric and body composition parameters and resting energy expenditure were measured. Fasting circulating leptin, T3, SHBG and UCP2 levels were measured. Subjects were divided into three groups: Group І (BMI>30 and low resting energy expenditure, 16 subjects), group II (BMI>30 and normal resting energy expenditure, 17 subjects), and group ІІІ (control group, 16 non-obese subjects). RESULT: It was found that obese subjects who had higher SHBG and leptin levels were at risk for high levels of UCP2. A significant association was found between T3 and REE. Obese subjects with higher concentrations of UCP2 and SHBG had decreased resting energy expenditure. A significant association was observed between SHBG and leptin in group І (r=0.90, p<0.0001) and group ІІ (r=0.83, p<0.0001). Moreover, a significant association was found between T3 and SHBG in group І (r=-0.69, P=0.003). CONCLUSION: Changes of the UCP2, leptin, and thyroid hormone (T3) levels may be related to SHBG levels. Thus, lower leptin and T3 levels may decrease SHBG in obese women. Therefore, lower SHBG, leptin, T3 and UCP2 levels may decrease the REE level in obese women.

Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation.

BACKGROUND: Excessive reactive oxygen species from endothelial mitochondria in type 2 diabetes individuals (T2DM) may occur through multiple related mechanisms, including production of mitochondrial reactive oxygen species (mtROS), inner mitochondrial membrane (Δψm) hyperpolarization, changes in mitochondrial mass and membrane composition, and fission of the mitochondrial networks. Inner mitochondrial membrane proteins uncoupling protein-2 (UCP2) and prohibitin (PHB) can favorably impact mtROS and mitochondrial membrane potential (Δψm). Circulating levels of UCP2 and PHB could potentially serve as biomarker surrogates for vascular health in patients with and without T2DM. METHODS: Plasma samples and data from a total of 107 individuals with (N = 52) and without T2DM (N = 55) were included in this study. Brachial artery flow mediated dilation (FMD) was measured by ultrasound. ELISA was performed to measure serum concentrations of PHB1 and UCP2. Mitochondrial membrane potential was measured from isolated leukocytes using JC-1 dye. RESULTS: Serum UCP2 levels were significantly lower in T2DM subjects compared to control subjects (3.01 ± 0.34 vs. 4.11 ± 0.41 ng/mL, P = 0.04). There were no significant differences in levels of serum PHB. UCP2 levels significantly and positively correlated with FMDmm (r = 0.30, P = 0.03) in T2DM subjects only and remained significant after multivariable adjustment. Within T2DM subjects, serum PHB levels were significantly and negatively correlated with UCP2 levels (ρ = - 0.35, P = 0.03). CONCLUSION: Circulating UCP2 levels are lower in T2DM patients and correlate with endothelium-dependent vasodilation in conduit vessels. UCP2 could be biomarker surrogate for overall vascular health in patients with T2DM and merits additional investigation.

ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content in human skeletal muscle in the Gene SMART study.

Angiotensin-converting enzyme (ACE) is expressed in human skeletal muscle. The ACE I/D polymorphism has been associated with athletic performance in some studies. Studies have suggested that the ACE I/D gene variant is associated with ACE enzyme content in serum, and there is an interaction between ACE and uncoupling proteins 2 and 3 (UCP2 and UCP3). However, no studies have explored the effect of ACE I/D on ACE, UCP2, and UCP3 protein content in human skeletal muscle. Utilizing the Gene SMART cohort ( n = 81), we investigated whether the ACE I/D gene variant is associated with ACE enzyme content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and following a session of high-intensity interval exercise (HIIE). Using a stringent and robust statistical analyses, we found that the ACE I/D gene variant was associated with ACE enzyme content in blood ( P < 0.005) at baseline but not the ACE, UCP2, and UCP3 protein content in muscle at baseline. A single session of HIIE tended (0.005 < P < 0.05) to increase blood ACE content immediately postexercise, whereas muscle ACE protein content was lower 3 h after a single session of HIIE ( P < 0.005). Muscle UCP3 protein content decreased immediately after a single session of HIIE ( P < 0.005) and remained low 3 h postexercise. However, those changes in the muscle were not genotype dependent. In conclusion, The ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content of human skeletal muscle. NEW & NOTEWORTHY This paper describes the association between ACE I/D gene variant and ACE protein content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and after exercise in a large cohort of healthy males. Our data suggest that ACE I/D is a strong predictor of blood ACE content but not muscle ACE content.

Association between UCP polymorphisms and adipokines with obesity in Mexican adolescents.

BACKGROUND: It has been reported that the uncoupling proteins (UCPs) can contribute to energy metabolism, and are thus involved in the pathogenesis of obesity. The objective of the study was to analyze the association between UCP polymorphisms, clinical parameters and leptin and adiponectin plasma levels in an adolescent population with overweight and obesity. METHODS: We analyzed the UCP1 -3826 C/T, UCP2-866 G/A, Ala55Val and UCP3 -55 C/T polymorphisms and the levels of adipokines in adolescents with normal weight and with overweight or obesity. The study included 270 students aged between 12 and 18 years categorized according to the percentiles from Mexico City. Adipokines levels were measured by immunoassay methods and the UCP polymorphisms were determined using Taqman real-time polymerase chain reaction (RT-PCR). RESULTS: No significant differences were found in the UCP polymorphisms in seven inheritance models studied. Most of the significant differences in the clinical parameters were found under a recessive model, the UCP2 -866 polymorphism was associated with diastolic blood pressure (p=0.008), triglycerides (p=0.045), low-density lipoprotein-cholesterol (LDL-C) (p=0.003), high-density lipoprotein-cholesterol (HDL-C) (p=0.050) and plasma levels of leptin (p<0.001). Also, the obese group was found to have higher leptin levels and lower adiponectin levels in GA+AA vs. GG (recessive model). CONCLUSIONS: This study demonstrated a direct relationship between the clinical characteristics and UCP2-866 in a recessive model, associated with high levels of leptin and decreased levels of adiponectin in an obese or overweight Mexican adolescent population.

Association between uncoupling protein 2, adiponectin and resting energy expenditure in obese women with normal and low resting energy expenditure.

Obesity is recognized as the most prevalent metabolic disease worldwide. Decreases in energy expenditure may increase risk of obesity. One of the key regulators of energy balance is uncoupling protein2 (UCP2), a transporter protein presents in mitochondrial inner membrane. Moreover, adiponectin is the most abundant adipocytokine, it may play a role in energy metabolism and gene expression of UCP2. The aim of this study was to investigate potential associations between the level of uncoupling protein 2 and adiponectin and their relationship with REE (Resting Energy Expenditure) in obese women with normal and low resting energy expenditure. A total of 49 subjects (women, 25-50 years old), were included in current study, 16 subjects with BMI > 30 and low resting energy expenditure, 17 subjects with BMI > 30 and normal resting energy expenditure and 16 non-obese subjects as a control group. Anthropometric, body composition parameters and resting energy expenditure were measured. Plasma adiponectin, UCP2 protein and total protein in PBMC were determined. Measured resting energy expenditure in obese subjects with low REE was significantly lower than other groups. Plasma adiponectin in the obese subjects with low REE was significantly lower compared to normal weight group. There was a significant relationship between 'UCP2 protein/Total protein' ratio and plasma adiponectin in obese group with low REE and in three groups when we pooled. There was a significant association between REE and plasma adiponectin in three groups when we pooled. There was a significant association between plasma adiponectin and REE. Moreover, there was a significant relationship between UCP2 and REE.

UCP2 in early diagnosis and prognosis of sepsis.

OBJECTIVE: Sepsis, a systemic inflammatory response syndrome caused by infection, is a serious threat to the lives of patients. Sepsis can cause tissue hypoperfusion and septic shock which leads to organ dysfunction and death via a variety of mechanisms. Mitochondrial protein (UCP2) involves in immune response, regulation of oxidative stress, and maintenance of mitochondrial membrane potential as well as energy production. However, the role of UCP2 in sepsis remains to be further explored. PATIENTS AND METHODS: A total of 156 patients with sepsis from our hospital were included in this study (69 patients with sepsis and 87 patients with severe sepsis). A total of 69 healthy volunteers were included as controls. Levels of UCP2 in blood cells before and after treatment were measured using RT-PCR and Western blot. The correlation between levels of UCP2 and sepsis was analyzed. RESULTS: The level of UCPPC2 in blood cells of sepsis patients was significantly higher than that of healthy controls at both mRNA level and protein level. The expression level of UCP2 in blood cells of sepsis patients was significantly reduced after treatment, compared to that before treatment. No significant difference was found in the level of UCP2 in blood cells of healthy controls before and after treatment ((p=0.45). Also, the level of UCP2 in blood cells of patients with severe sepsis was significantly higher than that of patients with sepsis at the protein level (p<0.05). Moreover, a positive correlation was found between the level of UCP2 protein and the severity of sepsis. CONCLUSIONS: UCP2 in blood cells might be a specific biomarker for sepsis and the level of UCP2 is positively correlated with the severity of sepsis.

The effect of delivery type on uncoupling protein-2 levels.

OBJECTIVE: Uncoupling proteins (UCPs) are carrier proteins located in the mitochondrial inner membrane that disturb the proton gradient by re-transporting protons and that thus inhibit ATP synthesis. UCP-2 is found in in several tissues, particularly the brain. This study was performed to examine the effects of mode of delivery on UCP-2 in humans. METHODS: The study was performed prospectively. Cord blood specimens were collected for measurement of blood gasses, full-blood count, total and direct bilirubin levels and UCP-2. UCP-2 levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Results were expressed as nanogram per milliliter. RESULTS: The study was performed with 120 healthy term babies, 60 born by normal spontaneous vaginal delivery (NSVD) and 60 by cesarean/section (C/S). There was significant difference in UCP-2 levels between the two groups. UCP-2 levels were significantly higher in the cases born by NSVD then in the cases born by C/S. CONCLUSION: This study showed that a correlation exists between mode of delivery and UCP-2 in humans. As UCP-2 is described as playing a significant role in the formation of nerve cells and deficiency of this protein during development of the brain may lead to behavioral problems extending to adulthood, we think that increasing UCP-2 levels through normal delivery will protect all organs, and particularly the brain, against oxidative damage and play a role in preventing organ dysfunctions.