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1.
Biomedical and Environmental Sciences ; (12): 1045-1058, 2023.
Article in English | WPRIM | ID: wpr-1007880

ABSTRACT

OBJECTIVE@#In this study, the combined effect of two stressors, namely, electromagnetic fields (EMFs) from mobile phones and fructose consumption, on hypothalamic and hepatic master metabolic regulators of the AMPK/SIRT1-UCP2/FOXO1 pathway were elucidated to delineate the underlying molecular mechanisms of insulin resistance.@*METHODS@#Weaned Wistar rats (28 days old) were divided into 4 groups: Normal, Exposure Only (ExpO), Fructose Only (FruO), and Exposure and Fructose (EF). Each group was provided standard laboratory chow ad libitum for 8 weeks . Additionally, the control groups, namely, the Normal and FruO groups, had unrestricted access to drinking water and fructose solution (15%), respectively. Furthermore, the respective treatment groups, namely, the ExpO and EF groups, received EMF exposure (1,760 MHz, 2 h/day x 8 weeks). In early adulthood, mitochondrial function, insulin receptor signaling, and oxidative stress signals in hypothalamic and hepatic tissues were assessed using western blotting and biochemical analysis.@*RESULT@#In the hypothalamic tissue of EF, SIRT1, FOXO 1, p-PI3K, p-AKT, Complex III, UCP2, MnSOD, and catalase expressions and OXPHOS and GSH activities were significantly decreased ( P < 0.05) compared to the Normal, ExpO, and FruO groups. In hepatic tissue of EF, the p-AMPKα, SIRT1, FOXO1, IRS1, p-PI3K, Complex I, II, III, IV, V, UCP2, and MnSOD expressions and the activity of OXPHOS, SOD, catalase, and GSH were significantly reduced compared to the Normal group ( P < 0.05).@*CONCLUSION@#The findings suggest that the combination of EMF exposure and fructose consumption during childhood and adolescence in Wistar rats disrupts the closely interlinked and multi-regulated crosstalk of insulin receptor signals, mitochondrial OXPHOS, and the antioxidant defense system in the hypothalamus and liver.


Subject(s)
Humans , Rats , Animals , Adult , Rats, Wistar , Fructose/metabolism , Catalase , Receptor, Insulin/metabolism , AMP-Activated Protein Kinases/metabolism , Electromagnetic Fields/adverse effects , Sirtuin 1/metabolism , Cell Phone , Phosphatidylinositol 3-Kinases/metabolism , Forkhead Box Protein O1/metabolism , Uncoupling Protein 2
2.
Rev. chil. endocrinol. diabetes ; 16(3): 46-52, 2023. tab, ilus
Article in Spanish | LILACS | ID: biblio-1451956

ABSTRACT

El ambiente obesogénico promueve la obesidad al facilitar el acceso y consumo de una amplia variedad de alimentos palatables altos en calorías. La activación del receptor de GLP1 (GLP1R) reduce la ingesta de alimentos, enlentece el vaciamiento gástrico y promueve un balance energético negativo a través de su acción en distintos órganos como el músculo esquelético, disminuyendo así el peso corporal. La obesidad inducida por dieta alta en grasa disminuye el efecto anorexigénico de la administración sistémica vía intra-peritoneal de EX4 (agonista de GLP1R). Sin embargo, se desconoce si la exposición a un ambiente obesogénico previo a la manifestación de obesidad disminuye los efectos anorexigénicos de EX4 o un posible efecto de EX4 sobre marcadores de oxidación de ácidos grasos y termogénesis en músculo esquelético. El objetivo de esta investigación fue determinar el efecto a corto plazo de la dieta CAF, un modelo del ambiente obesogénico humano, sobre la capacidad de EX4 de reducir la ingesta y modular la expresión de marcadores proteicos de oxidación de ácidos grasos y termogénesis (CPT1 y UCP2) en músculo de ratones. Nuestros datos muestran que una inyección intraperitoneal de EX4 a ratones C57BL/6J alimentados con dieta CAF o dieta control durante 10 días no altera la ingesta calórica total, peso corporal, o la expresión de proteínas marcadoras de los procesos de beta-oxidación y de termogénesis (CPT1 y UCP2). Estos datos sugieren que protocolos alternativos de administración de EX4 son necesarios para observar los efectos fisiológicos de la activación de GLP1R.


The obesogenic environment promotes obesity by facilitating access to and consumption of a wide variety of palatable, high-calorie foods. Activation of the GLP1 receptor (GLP1R) reduces food intake, slows gastric emptying, and promotes a negative energy balance by acting on organs such as skeletal muscle, thus decreasing body weight. Obesity induced by a high-fat diet decreased the anorexigenic effect of intraperitoneal systemic administration of EX4 (GLP1R agonist). However, it is unknown whether exposure to an obesogenic environment before the manifestation of obesity diminishes the anorexigenic effects of EX4 or a possible effect of EX4 on markers of fatty acid oxidation and thermogenesis in skeletal muscle. This investigation aimed to determine the short-term effect of the CAF diet, a model of the human obesogenic environment, on the ability of EX4 to reduce intake and modulate the expression of protein markers of fatty acid oxidation and thermogenesis (CPT1 and UCP2) in mouse muscle. Our data show that intraperitoneal injection of EX4 to C57BL/6J mice fed CAF diet or control diet for ten days does not alter total caloric intake, body weight, or expression of proteins markers of beta-oxidation and thermogenesis processes (CPT1 and UCP2). These data suggest that alternative EX4 administration protocols are necessary to observe the physiological effects of GLP1R activation.


Subject(s)
Animals , Male , Mice , Diet/adverse effects , Exenatide/administration & dosage , Obesity/etiology , Obesity/metabolism , Oxidation-Reduction , Blotting, Western , Muscle, Skeletal/metabolism , Thermogenesis , Fatty Acids/metabolism , Glucagon-Like Peptide-1 Receptor/metabolism , Uncoupling Protein 2 , Irinotecan , Injections, Intraperitoneal , Mice, Inbred C57BL
3.
Neuroscience Bulletin ; (6): 15-24, 2019.
Article in English | WPRIM | ID: wpr-775480

ABSTRACT

Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha (PPAR-α), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-α and PPAR-γ was assessed in the nodose ganglion (NG) and the nucleus of the solitary tract (NTS). Hypertension induced by drinking high fructose (HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-α and PPAR-γ were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-α, the mitochondrial uncoupling protein 2 (UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats. These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.


Subject(s)
Animals , Male , Afferent Pathways , Antihypertensive Agents , Pharmacology , Baroreflex , Blood Pressure , Fenofibrate , Pharmacology , Oxidative Stress , PPAR gamma , Metabolism , Rats, Sprague-Dawley , Signal Transduction , Transcriptional Activation , Uncoupling Protein 2 , Metabolism , Up-Regulation
4.
Journal of Zhejiang University. Medical sciences ; (6): 143-149, 2018.
Article in Chinese | WPRIM | ID: wpr-687787

ABSTRACT

<p><b>OBJECTIVE</b>To explore the association between rs659366 polymorphisms and the outcomes of patients after surgery for colorectal cancer.</p><p><b>METHODS</b>The study was conducted among a cohort of 501 patients with primary colorectal cancer who had surgery in Sichuan Cancer Hospital during March 2010 and July 2013. The outcomes of the patients were followed up. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect rs659366 genotypes. The log-rank test was performed to analyze the effects of clinical features on patients' outcomes. The correlation between rs659366 polymorphisms and the outcomes of patients was analyzed using the Cox proportional hazard model.</p><p><b>RESULTS</b>In this study, the median of follow-up time was 44.23(0.13-78.53)months, and 101 out of 501 (20.2%) patients failed to follow-up. The log-rank test showed the tumor site, TNM stage, vascular invasion, perineural invasion and the preoperative carcino-embryonic antigen(CEA) level were significantly associated with the outcome of colorectal cancer (<0.05 or <0.01). The overall survival rate of patients with AA, GA and GG genotypes were 62.7%, 69.9% and 75.5%, respectively. Multivariate analysis according to Cox proportional hazard model taking the GG genotype as the reference indicated that the AA genotype increased risks for survival of patients (=1.823); under the dominant genetic model taking GG genotype as reference, GA+AA genotypes increased risks for the poorer outcomes of patients (=1.498); the addictive genetic model showed that allele A increased the hazard for the poorer outcomes (=1.787).</p><p><b>CONCLUSIONS</b>The rs659366 polymorphisms are significantly associated with the outcome of patients with colorectal cancer.</p>


Subject(s)
Humans , Colorectal Neoplasms , Genotype , Polymerase Chain Reaction , Polymorphism, Genetic , Proportional Hazards Models , Survival Rate , Uncoupling Protein 2
5.
Chinese journal of integrative medicine ; (12): 48-54, 2017.
Article in English | WPRIM | ID: wpr-301011

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of total flavonoids of Astmgali Radix (TFA) on liver cirrhosis induced with dimethylnitrosamine (DMN) in rats, and the effect on peroxisome proliferator-activated receptor γ (PPARγ), uncoupling protein 2 (UCP2) and farnesoid X receptor (FXR).</p><p><b>METHODS</b>Fifty-three Sprague-Dawley rats were randomly divided into a control group (10 rats) and a DMN group (43 rats). Rats in the DMN group were given DMN for 4 weeks and divided randomly into a model group (14 rats), a low-dosage TFA group (14 rats) and a high-dosage TFA group (15 rats) in the 3rd week. Rats were given TFA for 4 weeks at the dosage of 15 and 30 mg/kg in the low- and high-TFA groups, respectively. At the end of the experiment blood and liver samples were collected. Serum liver function and liver tissue hydroxyproline content were determined. hematoxylin-eosin (HE), Sirus red and immunohistochemical stainings of collagen I, smooth muscle actin (α-SMA) was conducted in paraffinembedded liver tissue slices. Real time polymerase chain reaction (PCR) was adopted to determine PPARγ, UCP2 and FXR mRNA levels. Western blot was adopted to determine protein levels of collagen I, α-SMA, PPARγ, UCP2 and FXR.</p><p><b>RESULTS</b>Compared with the model group, TFA increased the ratio of liver/body weight (low-TFA group P<0.05, high-TFA group P<0.01), improved liver biochemical indices (P<0.01 for ALT, AST, GGT in both groups, P<0.05 for albumin and TBil in the high-TFA group) and reduced liver tissue hydroxproline content (P<0.01 in both groups) in treatment groups significantly. HE staining showed that TFA alleviated liver pathological changes markedly and Sirus red staining showed that TFA reduced collagen deposition, alleviated formation and extent of liver pseudolobule. Collagen I and α-SMA immunohistochemical staining showed that staining area and extent markedly decreased in TFA groups compared with the model group. TFA could increase PPARγ, it regulated target UCP2, and FXR levels significantly compared with the model group (in the low-TFA group all P<0.05, in the high group all P<0.01).</p><p><b>CONCLUSION</b>TFA could improve liver function, alleviate liver pathological changes, and reduce collagen deposition and formation of liver pseudolobule in rats with liver cirrhosis. The antifibrotic effect of TFA was through regulating PPARγ signal pathway and the interaction with FXR.</p>


Subject(s)
Animals , Male , Actins , Metabolism , Blotting, Western , Body Weight , Collagen Type I , Metabolism , Dimethylnitrosamine , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Flavonoids , Pharmacology , Therapeutic Uses , Hydroxyproline , Metabolism , Liver , Pathology , Liver Cirrhosis , Blood , Drug Therapy , Genetics , Pathology , Organ Size , PPAR gamma , Genetics , Metabolism , Plant Extracts , Pharmacology , Therapeutic Uses , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Receptors, Cytoplasmic and Nuclear , Genetics , Metabolism , Uncoupling Protein 2 , Genetics , Metabolism
6.
Chinese Journal of Contemporary Pediatrics ; (12): 159-164, 2016.
Article in Chinese | WPRIM | ID: wpr-279879

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the correlation between uncoupling protein 2 (UCP2) expression and myocardial mitochondria injury in rats with sepsis induced by lipopolysaccharide (LPS).</p><p><b>METHODS</b>The rat model of sepsis was established through an intraperitoneal injection of LPS. Forty male Sprague-Dawley rats were randomly and equally divided into control group (an intraperitoneal injection of normal saline), sepsis 6 h group (LPS-6 h group), sepsis 12 h group (LPS-12 h group), sepsis 24 h group (LPS-24 h group), and sepsis 48 h group (LPS-48 h group). The serum and heart tissues were harvested at corresponding time points and myocardial mitochondria was extracted. The microplate reader was applied to measure creatine kinase (CK), creatine kinase-MB (CK-MB), and reactive oxygen species (ROS). Flow cytometry was applied to measure the degree of mitochondrial swelling and mitochondrial membrane potential (MMP). Western blot was used to measure the expression level of UCP2. Electron microscopy was applied to observe the morphological changes in heart tissues and myocardial mitochondria.</p><p><b>RESULTS</b>Compared with the control group, the LPS groups had significantly increased serum levels of CK, CK-MB, and myocardial ROS, as well as a significantly increased degree of mitochondrial swelling (P<0.05), and these values reached their peaks at 24 hours after LPS injection. The LPS groups had a significant decrease in MMP (P<0.05), which reached the lowest level at 24 hours after LPS injection. Western blot showed that the LPS groups had a significant increase in the expression level of myocardial UCP2 compared with the control group (P<0.05), which reached its peak at 24 hours after LPS injection. The results of electron microscopy showed mitochondrial swelling, partial rupture of the mitochondrial membrane, and cavity formation in rats in the LPS groups. The most severe lesions occurred in the LPS-24 h group. In rats with LPS, the ROS level in the myocardial mitochondria and the degree of mitochondrial swelling were positively correlated with the expression level of UCP2 (r=0.796 and 0.893, respectively; P<0.05), while MMP was negatively correlated with the expression level of UCP2 (r=-0.903, P<0.05).</p><p><b>CONCLUSIONS</b>In the rat model of sepsis, the myocardium and myocardial mitochondria have obvious injuries, and the expression level of UCP2 is closely correlated with mitochondrial injury. Therefore, UCP2 might play an important role in myocardial mitochondrial injury in sepsis.</p>


Subject(s)
Animals , Humans , Male , Rats , Cardiomyopathies , Genetics , Metabolism , Disease Models, Animal , Ion Channels , Genetics , Metabolism , Lipopolysaccharides , Mitochondria, Heart , Metabolism , Mitochondrial Proteins , Genetics , Metabolism , Myocardium , Metabolism , Rats, Sprague-Dawley , Sepsis , Genetics , Metabolism , Uncoupling Protein 2
7.
National Journal of Andrology ; (12): 973-976, 2015.
Article in Chinese | WPRIM | ID: wpr-304788

ABSTRACT

<p><b>OBJECTIVE</b>To explore whether the inhibitory effect of Genipin on uncoupling protein-2 (UCP-2) in mitochondria is involved in energy metabolism of androgen-independent PC3 prostate cancer cells.</p><p><b>METHODS</b>PC3 prostate cancer cells were cultured and treated with Genipin at the concentrations of 40, 80, and 160 μmol/L for 48 hours. Then the proliferation of the cells was detected by MTT assay, the expression of UCP-2 mRNA determined by RT-PCR, and the content of intracellular pyruvic acid (PA) and the activity of succinate dehydrogenase (SDH) in the mitochondria measured by visible spectrophotometry.</p><p><b>RESULTS</b>With the increased concentration of Genipin, the proliferative activity of the PC-3 cells, the expression level of UCP-2 mRNA, the content of intracellular PA and the activity of SDH in the cells were all decreased, namely, with the enhanced inhibitory effect of Genipin on UCP-2, a trend of reduction was observed in the proliferation of the cells, intracellular PA content, and SDH activity in the mitochondria.</p><p><b>CONCLUSION</b>Genipin is involved in the energy metabolism of androgen-independent PC3 prostate cancer cells by reducing the content of intracellular PA and the activity of SDH in the mitochondria, which may be associated with its inhibitory effect on UCP-2.</p>


Subject(s)
Humans , Male , Cell Line, Tumor , Energy Metabolism , Ion Channels , Metabolism , Iridoids , Pharmacology , Mitochondria , Metabolism , Mitochondrial Proteins , Metabolism , Prostatic Neoplasms , Metabolism , Pyruvic Acid , Metabolism , RNA, Messenger , Succinate Dehydrogenase , Metabolism , Uncoupling Protein 2
8.
Rev. cienc. salud (Bogotá) ; 12(2): 157-167, ago. 2014. ilus, tab
Article in Spanish | LILACS, COLNAL | ID: lil-715275

ABSTRACT

La obesidad es una enfermedad multifactorial que se relaciona con estilos de vida y factores medioambientales y genéticos. Uno de los genes candidatos de la obesidad es el UCP2. Su polimorfismo -866G/A se ha asociado con obesidad en algunas poblaciones. Sin embargo, se han reportado resultados contradictorios alrededor del mundo, lo cual indica la necesidad de nuevas investigaciones al respecto. Objetivo: Analizar el polimorfismo -866G/A del gen UCP2 asociado con obesidad en adultos de la ciudad de Valledupar. Materiales y métodos: Se estudiaron 103 individuos con sobrepeso u obesidad y 100 con normopeso. El polimorfismo de UCP2 -866G/A fue determinado por PCR-RFLP. Se evaluaron también medidas antropométricas, perfil de lipoproteínas y glucemia basal. Resultados: Se observó que el alelo mutado y su genotipo homocigoto fueron significativamente más frecuentes en pacientes con IMC > a 25 kg/m². [A: OR= 2,9 (IC 95%= 1,765-4,751) y AA: OR=5,8 (IC 95%= 1,264-2,745)]. No se encontraron diferencias significativas entre UCP2 -866G/A y las variables clínicas estudiadas en individuos obesos. Sin embargo, se observa que los sujetos con alelos y genotipos mutados presentaron cifras más elevadas de triglicéridos, glucemia e ICC y menor promedio de cHDL. Conclusiones: la mutación -866G/A del gen UCP2 se asocia a obesidad en la población estudiada y aunque no parece influir en las medidas antropométricas y bioquímicas en sujetos obesos, podría estar relacionado con aumento de ICC, glucosa y triglicéridos y disminución de cHDL.


Obesity is a multifactorial disease that is related to lifestyles, and environmental and genetic factors. One of the candidate genes for obesity is the UCP2. Its polymorphism -866G/A was associated with obesity in some populations. However, conflicting results have been reported around the world, indicating the need for further investigations. Objective: To analyze the polymorphism -866G/A UCP2 gene associated with obesity in adults in the city of Valledupar. Materials and methods: We studied 103 overweight or obese individuals and 100 normal weight. The polymorphism of UCP2 -866G/A was determined by PCR-RFLP. Anthropometric measures were also evaluated, lipoprotein profile and fasting glucose. Results: We found that the mutated allele and homozygous genotype were significantly more frequent in patients with BMI > 25 kg/m². [A: OR = 2.9 (95% CI= 1,765 to 4,751 ) and AA: OR= 5.8 (95% CI = 1,264 to 2,745)]. No significant differences were found between UCP2 -866G/A and the clinical variables studied in obese individuals. However it is observed that subjects with mutated alleles and genotypes had higher triglycerides, glucose and ICC and lower average HDL cholesterol. Conclusions: mutation -866G/A UCP2 gene is associated with obesity in the population studied, and although it seems to influence the anthropometric and biochemical measures in obese subjects could be related to increased ICC, glucose and triglycerides and decreased HDL.


A obesidade é uma doença multifatorial que se relaciona com estilos de vida, e fatores meio ambientais e genéticos. Um dos genes candidatos da obesidade é o UCP2. Seu polimorfismo -866G/A tem se associado com obesidade em algumas populações. No entanto, tem se reportado resultados contraditórios ao redor do mundo, o qual indica a necessidade de novas pesquisas a respeito. Objetivo: analisar o polimorfismo -866G/A do gene UCP2 associado com obesidade em adultos da cidade de Valledupar. Materiais e métodos: estudaram-se 103 indivíduos com excesso de peso ou obesidade e 100 com normopeso. O polimorfismo UCP2 -866G/A foi determinado por PCR-RFLP. Avaliaram-se também medidas antropométricas, perfil de lipoproteínas e glicemia basal. Resultados: observou-se que o alelo mudado e seu genotipo homozigoto foram significativamente mais frequentes em pacientes com IMC > a 25 Kg/m2. (A: OR= 2,9 (IC 95%= 1,765-4,751) y AA: OR=5,8 (IC 95%= 1,264-2,745)). Não se encontraram diferenças significativas entre UCP2 -866G/A e as variáveis clínicas estudadas em indivíduos obesos. No entanto, observa-se que os sujeitos com alelos e genótipos mudados apresentaram cifras mais elevadas de triglicerídeos, glicemia, ICC e menor média de cHDL. Conclusões: a mutação -866G/A do gene UCP2 associa-se a obesidade na população estudada, e ainda que não parecesse influir nas medidas antropométricas e bioquímicas em sujeitos obesos, poderia estar relacionado com aumento de ICC, glicose, triglicerídeos e diminuição de cHDL.


Subject(s)
Humans , Polymorphism, Genetic , Data Interpretation, Statistical , Colombia , Uncoupling Protein 2 , Obesity
9.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 796-800, 2014.
Article in English | WPRIM | ID: wpr-331142

ABSTRACT

Cardiotrophin-1 (CT-1) activates a distinct form of cardiac muscle cell hypertrophy in which the sarcomeric units are assembled in series. The aim of the study was to determine the expression pattern of sarcomeric contractile protein α-actin, specialized cytoskeletal protein α-actinin and mitochondrial uncoupling protein-2 (UCP2) in myocardial remodeling induced by chronic exposure to CT-1. Kunming mice were intraperitoneally injected with carboxy-terminal polypeptide (CP) of CT-1 (CT-1-CP, 500 μg·kg(-1)· day(-1)) for 1, 2, 3 and 4 week (s), respectively (4 groups obtained according to the injection time, n=10 each, with 5 males and 5 females in each group). Those injected with physiological saline for 4 weeks served as controls (n=10, with 5 males and 5 females). The heart tissues of mice were harvested at 1, 2, 3 or 4 week (s). Immunohistochemistry (IHC) and Western blotting (WB) were used to detect the distribution and expression of sarcomeric α-actin, α-actinin and mitochondrial UCP2 in myocardial tissues. IHC showed that α-actin was mainly distributed around the nuclei of cardiomyocytes, α-actinin concentrated around the striae and UCP2 scattered rather evenly in the plasma. The expression of α-actin was slightly greater than that of α-actinin and UCP2 in the control group (IHC: χ(2)=6.125; WB: F=0.249, P>0.05) and it gradually decreased after exposure to CT-1-CP. There was no significant difference in the expression of α-actin between the control group and the CT-1-CP-treated groups (χ (2)=7.386, P>0.05). But Western blotting revealed significant difference in the expression of α-actin between the control group and the 4-week CT-1-CP-treated group (F=2.912; q=4.203, P<0.05). Moreover, it was found that the expression of α-actinin increased stepwise with the exposure time in CT-1-CP-treated groups and differed significantly between CT-1-CP-treated groups and the control group (ICH: χ (2)=21.977; WB: F=50.388; P<0.01). The expression of UCP2 was initially increased (WB: control group vs. 1- or 2-week group, q values: 5.603 and 9.995, respectively, P<0.01) and then decreased (WB: control group vs. 3-week group, q=4.742, P<0.01; control group vs. 4-week group, q=0.558, P>0.05). It was suggested that long-term exposure to CT-1-CP could lead to the alteration in the expression of sarcomeric α-actin, α-actinin and mitochondrial UCP2. The different expressions of sarcomeric structure proteins and mitochondrial UCP2 may be involved in myocardial remodeling.


Subject(s)
Animals , Female , Male , Mice , Actinin , Actins , Cardiomegaly , Metabolism , Pathology , Cytokines , Pharmacology , Gene Expression Regulation , Ion Channels , Mitochondrial Proteins , Myocardium , Metabolism , Pathology , Sarcomeres , Metabolism , Pathology , Uncoupling Protein 2
10.
Chinese Journal of Contemporary Pediatrics ; (12): 851-855, 2014.
Article in Chinese | WPRIM | ID: wpr-254185

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of uncoupling protein 2 (UCP2)-siRNA on the inflammatory response of rat cardiomyocytes (H9C2) induced by septic serum and to investigate the possible role of UCP2 in the development of septic cardiomyopathy.</p><p><b>METHODS</b>Serum samples were separately collected from normal rats and septic rats. Cultured rat cardiac cells (H9C2) were randomly divided into blank control, normal serum, 10% septic serum, UCP2-siRNA+10% septic serum and negative siRNA+10% septic serum groups. Stimulation with 10% septic serum was performed for 12 hours in relevant groups. The mRNA expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) was measured by RT-PCR. The expression of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor-kappa B (NF-κB) was measured by Western blot.</p><p><b>RESULTS</b>The expression levels of p-p38 and NF-κB in the UCP2-siRNA+10% septic serum group were significantly higher than in the 10% septic serum group (P<0.05). The UCP2-siRNA+10% septic serum group had a significantly higher TNF-α mRNA expression than the 10% septic serum group (P<0.01), but IL-1β mRNA expression showed no significant difference between the two groups.</p><p><b>CONCLUSIONS</b>UCP2 plays a regulatory role in the activation of p38 MAPK and NF-κB and the expression of downstream inflammatory mediators in H9C2 cells stimulated with septic serum.</p>


Subject(s)
Animals , Male , Rats , Cardiomyopathies , Cells, Cultured , Inflammation , Interleukin-1beta , Genetics , Ion Channels , Genetics , Physiology , Mitochondrial Proteins , Genetics , Physiology , Myocytes, Cardiac , Metabolism , NF-kappa B , Metabolism , RNA, Small Interfering , Genetics , Rats, Sprague-Dawley , Sepsis , Blood , Tumor Necrosis Factor-alpha , Genetics , Uncoupling Protein 2 , p38 Mitogen-Activated Protein Kinases , Metabolism
11.
Chinese Journal of Applied Physiology ; (6): 363-367, 2013.
Article in Chinese | WPRIM | ID: wpr-235357

ABSTRACT

<p><b>OBJECTIVE</b>To explore the expression changes of mRNA and protein of uncoupling protein 2 (UCP2) in adipose tissues and uncoupling protein 3 (UCP3) in muscle tissues of rats which were treated with repeated fasting/refeeding and followed by fed with high-fat diet, and their possible mechanism on lipid metabolism.</p><p><b>METHODS</b>The model of repeating fasting/refeeding rats (repeated cycles of 1-day fasting and 1-day refeeding for 6 weeks fed with common-fat diet, RFR) was designed. At the end of the 6th week, the RFR rats were switched to high-fat diet every day (RFR-CF/HF). Moreover, the control rats were randomly divided into two groups and then fed with high-fat diet (HF) and common-fat diet (CF) respectively for 6 weeks. All rats were killed at the end of the 6th and the 12th week, serum and plasma samples were taken from abdominal aorta, and then the concentration of serum lipids, glucose, free fatty acid (FFA), and plasma insulin were measured. The histomorphological changes of liver tissues were observed by HE staining. The expression level of mRNA and protein of UCP2 in adipose tissues and UCP3 in muscle tissues was respectively measured by RT-PCR and Western blot.</p><p><b>RESULTS</b>(1) The concentration of serum glucose in RFR group was significantly lower than that in control group (P < 0.05), while the concentration of serum FFA, expression level of UCP2 mRNA, UCP3 mRNA and protein were significantly higher than those in control group (P < 0.05). (2) The concentration of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and plasma insulin in RFR-CF/HF group was significantly lower than that in HF group, but significantly higher than that in CF group (P < 0.05). The concentration of serum FFA was significantly lower than that of HF and CF groups (P < 0.01). The expression level in UCP2, UCP3 mRNA and protein was significantly higher than that of HF group, but significantly lower than that of CF group (P < 0.05).</p><p><b>CONCLUSION</b>The feeding pattern of repeated fasting/refeeding can decrease the obese degree induced by high-fat diet, increase the mRNA and protein expression of UCP2 in adipose tissues and UCP3 in muscle tissues, up-regulate the proton leak caused by obesity, and improve the rate of basic energy metabolism in rats.</p>


Subject(s)
Animals , Male , Rats , Adipose Tissue , Metabolism , Fasting , Metabolism , Feeding Methods , Ion Channels , Metabolism , Lipid Metabolism , Mitochondrial Proteins , Metabolism , Muscles , Metabolism , Obesity , Metabolism , Rats, Sprague-Dawley , Uncoupling Protein 2 , Uncoupling Protein 3
12.
Chinese Journal of Applied Physiology ; (6): 376-384, 2013.
Article in Chinese | WPRIM | ID: wpr-235354

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effects of beta3-adrenergic receptor(beta3-AR) antagonist on myocardial uncoupling protein 2 (UCP2) expression and energy metabolism in chronic heart failure rats.</p><p><b>METHODS</b>Seven weight-matched normal adult rats (control group), 18 isoproterenol (ISO) induced heat failure (HR) rats (ISO group) and 21 ISO induced heart failure rats but received specific beta3-AR inhibitor SR59230A (ISO+ SR59230A group) for 6 weeks were included in this research. At the end of the study, echocardiography was performed, the ratio of left ventricular weight and body weight (LVW/BW) was calculated. The expression of beta3-AR ad UCP2 mRNA in myocardium were detected by reverse transcription-polymerase chain reaction (RT-PCR), the UCP2 protein in myocardium were detected by Western blot. The myocardial contents of creatine phosphate (PCr) and adenosine triphosphate (ATP) were measured by high performance liquid chromatography (HPLC).</p><p><b>RESULTS</b>Compared with control group, the cardiac function was significantly reduced and myocardial beta3-AR mRNA significantly increased, UCP2 mRNA and protein were also significantly increased in ISO group, this change could be attenuated by the treatment with SR59230A, and the expression of myocardial UCP2 protein negatively correlated with the ratio of PCr/ATP.</p><p><b>CONCLUSION</b>In the chronic stage of HF, the expression of UCP2 increases, which causes myocardial energy shortage, SR59230A improves myocardia energy efficiency and cardiac function by means of suppressing the expression of UCP2.</p>


Subject(s)
Animals , Male , Rats , Adrenergic Antagonists , Pharmacology , Energy Metabolism , Heart Failure , Metabolism , Ion Channels , Metabolism , Mitochondrial Proteins , Metabolism , Myocardium , Metabolism , Rats, Wistar , Receptors, Adrenergic, beta-3 , Metabolism , Uncoupling Protein 2
13.
Chinese Medical Journal ; (24): 3151-3155, 2013.
Article in English | WPRIM | ID: wpr-263509

ABSTRACT

<p><b>OBJECTIVE</b>To review the current advances on the role of uncoupling protein (UCP) in the pathogenesis and progress of nonalcoholic fatty liver disease (NAFLD).</p><p><b>DATA SOURCES</b>A comprehensive search of the PubMed literature without restriction on the publication date was carried out using keywords such as UCP and NAFLD.</p><p><b>STUDY SELECTION</b>Articles containing information related to NAFLD and UCP were selected and carefully analyzed.</p><p><b>RESULTS</b>The typical concepts, up-to-date findings, and existing controversies of UCP2 in NAFLD were summarized. Besides, the effect of a novel subtype of UCP (hepatocellular down regulated mitochondrial carrier protein, HDMCP) in NAFLD was also analyzed. Finally, the concept that any mitochondrial inner membrane carrier protein may have, more or less, the uncoupling ability was reinforced.</p><p><b>CONCLUSIONS</b>Considering the importance of NAFLD in clinics and UCP in energy metabolism, we believe that this review may raise research enthusiasm on the effect of UCP in NAFLD and provide a novel mechanism and therapeutic target for NAFLD.</p>


Subject(s)
Animals , Humans , Fatty Acids, Nonesterified , Metabolism , Fatty Liver , Metabolism , Ion Channels , Physiology , Mitochondrial Proteins , Chemistry , Physiology , Non-alcoholic Fatty Liver Disease , Uncoupling Protein 2
14.
Chinese journal of integrative medicine ; (12): 775-781, 2012.
Article in English | WPRIM | ID: wpr-289663

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the antiobesity effect of Jueming Prescription (JMP), a Chinese herbal medicine formula, and its influence on mRNA expressions of beta3 adrenergic receptor (beta3-AR) and uncoupling protein-2 (UCP-2) in adipose tissue of diet-induced obese rats.</p><p><b>METHODS</b>Fifty male Sprague-Dawley rats were randomly divided into the normal control group (n =8) that was on a standard chow diet, and the obese model group (n =42) that was on a diet of high fat chow. Two weeks after the high fat diet, 29 obese rats in the obese model group were further randomly divided into 3 groups: the untreated obese model group (n =9), the metformin group (n =10, metformin 300 mg kg⁻¹ day)⁻¹, and the JMP group (n =10, JMP 4 g kg⁻¹ day⁻¹). After 8-week treatment, body weight, wet weight of visceral fat, and percentage of body fat (PBF) were measured. The levels of fasting blood glucose, serum lipids, and insulin were assessed, and insulin sensitivity index (ISI) was calculated. The adipose tissue section was stained with hematoxylin-Eosin, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expressions of beta3-AR and UCP-2 from the peri-renal fat tissue were determined by real-time reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Compared with the obese model group, treatment with JMP resulted in significantly lower body weight, wet weight of visceral fat, PBF, and diameter of adipocytes, and significantly higher level of high-density lipoprotein cholesterol, ISI (all P<0.01), JMP increased the mRNA expressions of beta3-AR and UCP-2 from perirenal fat tissue (P <0.05, P<0.01).</p><p><b>CONCLUSIONS</b>JMP could reduce body weight and adipocyte size; and the effect was associated with the up-regulation of beta3-AR and UCP-2 expressions in the adipose tissue and improvement of insulin sensitivity.</p>


Subject(s)
Animals , Male , Rats , Adipocytes , Metabolism , Pathology , Adiposity , Blood Glucose , Metabolism , Body Weight , Cell Size , Diet, High-Fat , Drugs, Chinese Herbal , Pharmacology , Epididymis , Pathology , Fasting , Blood , Gene Expression Regulation , Insulin , Blood , Intra-Abdominal Fat , Metabolism , Pathology , Ion Channels , Genetics , Metabolism , Lipids , Blood , Mitochondrial Proteins , Genetics , Metabolism , Obesity , Blood , Genetics , Pathology , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Receptors, Adrenergic, beta-3 , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Uncoupling Protein 2 , Weight Loss
15.
Chinese Journal of Hepatology ; (12): 131-135, 2012.
Article in Chinese | WPRIM | ID: wpr-239291

ABSTRACT

To establish the Chang liver cell line stably overexpressing human uncoupling protein 2 (UCP2) and observe the effect of UCP2 on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). The Chang liver cell line was transfected with recombinant plasmid containing full-length human UCP2 cDNA (pcDNA3.1-hUCP2) or pcDNA3.1 empty vector. The stable cell line was established by antibiotic screening with Zeocin. UCP2 expression was detected by Western blotting and immunocytochemistry. The UCP2 overexpressing cells were pretreated with genipin at various doses (25, 50 and 100 munol/L). MMP and intracellular ROS were detected by fluorescence spectrophotometry. The total normalized protein content in UCP2 overexpressing cells was 1.6-fold higher than that in unmanipulated normal cells. The fluorescence intensities of Rhodamine123 and DCFH-DA in UCP2 overexpressing Chang liver cells (11.11+/-2.76 and 4.97+/-0.62, respectively) were significantly lower than those in unmanipulated normal cells (15.56+/-2.55, P less than 0.01 and 6.14+/-1.25, P less than 0.05, respectively) and in cells transfected with empty vector (16.11+/-2.93, P less than 0.01 and 6.23+/-1.13, P less than 0.05, respectively). Treatment of UCP2 overexpressing cells with 25, 50 and 100 munol/L genipin caused a dose-dependent increase in fluorescence intensities of Rhodamine123 (14.89+/-2.89, 17.89+/-2.93 and 24.00+/-2.55, respectively, all P less than 0.01) and DCFH-DA (9.16+/-0.78, 10.84+/-1.09 and 11.83+/-1.25, respectively, all P less than 0.01). The Chang liver cell line stably overexpressing UCP2 was established successfully. Using this cell system, UCP2 was found to play a role in mitochondrial function by regulating MMP and ROS.


Subject(s)
Humans , Cell Line , Hepatocytes , Metabolism , Ion Channels , Membrane Potential, Mitochondrial , Mitochondrial Proteins , Reactive Oxygen Species , Metabolism , Uncoupling Protein 2
16.
Journal of Southern Medical University ; (12): 726-729, 2012.
Article in Chinese | WPRIM | ID: wpr-269011

ABSTRACT

<p><b>OBJECTIVE</b>To observe the expression of SIRT1 and mitochondrial uncoupling protein 2 (UCP2) in the liver of rats with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver (NAFLD) and explore the possible pathogenesis of T2DM and NAFLD.</p><p><b>METHODS</b>Twenty-four male SD rat were randomized equally into control group and T2DM and NAFLD group (MC group), fed with standard diet and high-fat and high-sugar diet, respectively. At 12 weeks, the rats in MC group received a single dose of STZ (30 mg/kg) injected into the abdominal cavity for pancreatic islet destruction, and those in the control group received an equivalent volume of citric acid buffer. At 14 weeks, the body weight, FBG, hepatic function, blood lipid levels, FFAs, FINs and HOMA-IR of the rats were measured, and the liver pathology was examined with HE staining. The expression of SIRT1 and UCP2 in the rat liver was detected by immunohistochemistry and real-time quantitative PCR.</p><p><b>RESULTS</b>At 14 weeks, FBG, ALT, AST, TC, TG, LDL-C, VLDL, FFAs, FINs and HOMA-IR were significantly higher and HDL-C was significantly lower in MC group than in the control group (P<0.05). Pathological examination showed good structural integrity of the liver in the control group, and the liver cells were closely arranged with rich cytoplasm and round cell nuclei; in MC group, moderate to severe fatty liver was detected, and the liver cells showed severe ballooning degeneration and contained lipid vacuoles in the cytoplasm. The expression of SIRT1 was significantly lower and UCP2 significantly higher in MC group than in the control group (P<0.05).</p><p><b>CONCLUSION</b>The expression of SIRT1 is significantly lowered and UCP2 increased in the liver of rats with T2DM and NAFLD.</p>


Subject(s)
Animals , Male , Rats , Diabetes Mellitus, Type 2 , Metabolism , Fatty Liver , Metabolism , Ion Channels , Metabolism , Liver , Metabolism , Mitochondrial Proteins , Metabolism , Non-alcoholic Fatty Liver Disease , Rats, Sprague-Dawley , Sirtuin 1 , Metabolism , Uncoupling Protein 2
17.
Chinese Medical Journal ; (24): 2746-2750, 2011.
Article in English | WPRIM | ID: wpr-292812

ABSTRACT

<p><b>BACKGROUND</b>Type 2 diabetes mellitus (T2DM) results from the complex association of insulin resistance and pancreatic β-cell failure. Recent studies have shown that patients diagnosed with T2DM present with a significant decrease in β-cell function, which can be further compromised during the progression of the disease. Several mechanisms have been shown to play a role in this process such as glucotoxicity and lipotoxicity, which contribute to accelerating insulin secretion. In this regard, Chinese medicine has a certain advantage. This experiment was performed to observe the effect of a Chinese medicine named Kaiyuqingre formula (KYQRF) on β-cell function and its mechanisms of action therein.</p><p><b>METHODS</b>High glucose was used to set up a model of β-cell function failure. At the same time, medicated serum of KYQRF with different doses were administered to the cells. Rosiglitazone was taken as a control to observe the changes in insulin secretion, ATP-sensitive K(+) channels (K(ATP) channel) and uncoupling protein-2 (UCP-2) in each group.</p><p><b>RESULTS</b>KYQRF had some effects on the insulin secretion. In a low glucose environment, no effective change in insulin secretion was observed (P > 0.05). However, insulin levels increased significantly when INS-1 cells were exposed to a high glucose environment (P < 0.05). KYQRF could also enhance cell viability (P < 0.05) in an effect similar to rosiglitazone. Although KYQRF had no effect on inwardly rectifying potassium channels (Kir6.2) (P > 0.05), it could decrease the overexpression of both UCP-2 and sulfonylurea receptor 1 (P < 0.05).</p><p><b>CONCLUSION</b>KYQRF can protect islet function by decreasing UCP-2 and sulfonylurea receptor 1.</p>


Subject(s)
Animals , Male , Rats , ATP-Binding Cassette Transporters , Genetics , Cell Survival , Drugs, Chinese Herbal , Pharmacology , Glucose , Pharmacology , Insulin , Bodily Secretions , Insulin-Secreting Cells , Cell Biology , Metabolism , Ion Channels , Genetics , Mitochondrial Proteins , Genetics , Potassium Channels, Inwardly Rectifying , Genetics , Rats, Sprague-Dawley , Receptors, Drug , Genetics , Sulfonylurea Receptors , Thiazolidinediones , Pharmacology , Uncoupling Protein 2
18.
Chinese journal of integrative medicine ; (12): 205-211, 2011.
Article in English | WPRIM | ID: wpr-308702

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effect of berberine on uncoupling protein-2 (UCP2) mRNA and protein expressions in the hepatic tissue of non-alcoholic fatty liver disease (NAFLD) in rats, and to explore the molecular mechanism.</p><p><b>METHODS</b>To establish the NAFLD rat model; the rats were fed by high fat forage and were randomly divided into four groups: normal group, model group, berberine high-dose group (324 mg/kg), and berberine low-dose group (162 mg/kg). After treatment for 12 weeks, the expression of UCP2 mRNA in the liver tissue was analyzed by semiquantitative reverse transcription polymerase chain reaction (RT-RTPCR). The expression level of UCP2 protein in the liver tissue was examined by immunohistochemistry. Total PCR). cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) contents in blood serum, and TG and TC contents in the liver were detected by an automatic biochemical analyzer. The other is to observe the axungia degree of the liver.</p><p><b>RESULTS</b>The expression of UCP2 mRNA and positive cell numbers in the liver tissue were dramatically increased in the model group (P<0.01). Lipid in the serum and hepatic tissues increased significantly, and the liver was fatty. But in the treatment groups, the expression levels of mRNA and UCP2 proteins were significantly down-regulated (P<0.01). Liver steatosis was improved.</p><p><b>CONCLUSIONS</b>Berberine can down-regulate the expression levels of UCP2 mRNA and UCP2 proteins of hepatic tissue in NAFLD rats. It can promote the recovery of hepatocyte steatosis and improve lipid metabolism disorder in NAFLD rats. Berberine shows a potential therapeutic effect on NAFLD.</p>


Subject(s)
Animals , Male , Rats , Berberine , Pharmacology , Cholesterol , Metabolism , Disease Models, Animal , Fatty Liver , Genetics , Metabolism , Pathology , Gene Expression Regulation , Ion Channels , Genetics , Metabolism , Lipids , Blood , Liver , Metabolism , Pathology , Mitochondrial Proteins , Genetics , Metabolism , Non-alcoholic Fatty Liver Disease , Proteins , Metabolism , RNA, Messenger , Metabolism , Rats, Sprague-Dawley , Triglycerides , Metabolism , Uncoupling Protein 2
19.
Chinese Journal of Hepatology ; (12): 55-57, 2011.
Article in Chinese | WPRIM | ID: wpr-290652

ABSTRACT

To investigate the relationship between uncoupling protein 2 (UCP2) expression and the damage caused by oxygen free radicals in acute liver failure rat models. Thirty-five male Sprague-Dawley rats were randomly divided into two groups: the control group (15 rats) and liver failure group (20 rats). The rats were injected intraperitoneally with thioacetamide (TAA) to induce models of acute liver failure. The levels of endotoxin (ET) were detected by double antibody sandwich enzyme-linked immunosorbent assay. The expression of liver UCP2 mRNA was detected by reverse transcription polymerase chain reaction. The superoxide dismutase (SOD) and malonaldehyde (MDA) were detected by spectrophotometry. The expression of UCP2 protein was observed by immunohistochemistry. The data of the two groups were compared using Mann-Whitney U test or ANOVA. The expression of UCP2 mRNA in liver failure group was higher as compared to the control group (P value is less than 0.01); the level of MDA and endotoxin of liver failure group were higher than that of the control group (P value is less than 0.01). SOD of the liver failure group was lower (P value is less than 0.01). There was a certain correlation between UCP2 mRNA expression and ET, SOD and MDA (r = 0.952, -0.667, 0. 634 respectively, P value is less than 0.05 or 0.01). UCP2 is highly expressed in the livers of liver failure rats. A certain correlation perhaps existed between the expression of UCP2 mRNA and the serous SOD, MDA and ET.


Subject(s)
Animals , Male , Rats , Endotoxins , Ion Channels , Metabolism , Liver , Metabolism , Liver Failure, Acute , Metabolism , Malondialdehyde , Mitochondrial Proteins , Metabolism , Rats, Sprague-Dawley , Reactive Oxygen Species , Superoxide Dismutase , Uncoupling Protein 2
20.
Chinese Medical Journal ; (24): 2416-2423, 2010.
Article in English | WPRIM | ID: wpr-237439

ABSTRACT

<p><b>BACKGROUND</b>Uncoupling protein (UCP) 2 is related to the dysfunction of beta cells induced by fatty acids. However, whether UCP2 has similar effects on alpha cell is still not clear. This study aimed to investigate the effects of UCP2 and its possible mechanisms in lipotoxicity-induced dysfunction of pancreatic alpha cells.</p><p><b>METHODS</b>The alpha TC1-6 cells were used in this study to evaluate the effects of palmitate and/or UCP2 inhibit factors on the glucagon secretory function, glucagon content, the glucagon mRNA level and the nitrotyrosine level in the supernatant. Meantime, the expression levels of UCP2 and peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1 alpha) were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Furthermore, the possible relationship between UCP2 and insulin signal transduction pathway was analyzed.</p><p><b>RESULTS</b>Palmitate stimulated alpha cell glucagon secretion and the expression of UCP2 and PGC-1 alpha, which could be partially decreased by the inhibition of UCP2. Palmitate increased nitrotyrosine level and suppressed insulin signal transduction pathway in alpha cells. Inhibition of UCP2 influenced the effects of free fatty acid on alpha cells and may relate to glucagon secretion.</p><p><b>CONCLUSION</b>UCP2 played an important role on alpha cell dysfunction induced by free fatty acid in vitro, which may be related to its effects on oxidative stress and insulin signal transduction pathway.</p>


Subject(s)
Animals , Mice , Cells, Cultured , Glucagon , Bodily Secretions , Glucagon-Secreting Cells , Physiology , Insulin , Pharmacology , Insulin Receptor Substrate Proteins , Metabolism , Ion Channels , Genetics , Physiology , Iridoid Glycosides , Pharmacology , Iridoids , Mitochondrial Proteins , Genetics , Physiology , Oxidative Stress , Palmitic Acid , Toxicity , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Phosphorylation , RNA, Messenger , Signal Transduction , Trans-Activators , Genetics , Physiology , Transcription Factors , Tyrosine , Metabolism , Uncoupling Protein 2
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