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Objective To study the β3-adrenoceptor (β3-AR) in heart and lungs of elderly heart failure (HF) rats.Methods Forty-eight elderly HF Wistar rats were included in this study.A HF model of rats was established by ligating the aorta.The rats were divided into sham operation group (n=24) and HF group (n=24).The rats in each group were further divided into 4 subgroups at weeks 5,7,9 and 11 after operation (6 in each group).The hemodynamics,pathology and expression of β3-AR mRNA and protein in heart and lungs were detected at weeks 5,7,9 and 11 respectively after operation.Results The heart rate,LVESP,and dp/dtmax were significantly lower in HF group than in sham operation group at weeks 9 and 11 after operation while the LVEDP was significantly higher in HF group than in sham operation group at weeks 5,7,9 and 11 after operation (P＜0.01).Pulmonary edema occurred at week 7 after operation and myocardial necrosis was detected at week 9 after operation.The expression level of β3-AR mRNA in lungs was significantly lower in HF group at weeks 5,7,9 and 11 than at week 2 after operation (P＜0.05).The expression level of β3-AR mRNA in heart was significantly higher in HF group than in sham operation group at weeks 9 and 11 after operation (1.21±0.26 vs 0.98±0.22,1.26±0.23 vs 1.05±0.24,P＜0.01).Conclusion The β3-AR mRNA expression is downregulated in the lungs and upregulated in the heart.
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Objective To study the mechanism of β3 adrenoceptor (β3-AR) activation underlying cholesterol efflux by activating or inhibiting the β3-AR of HepG2 cells.Methods Cultured HepG2 cells were randomly divided into control group,β3-AR agonist group and β3-AR antagonist group.Serum levels of apoA-Ⅰ,apoA-Ⅱ,and β3-AR in supernatant fluid,and cholesterol,free cholesterol,cholesterol ester in HepG2 cells were measured by ELISA.Cholesterol efflux from macrophages was tested by 3H-labled cholesterol.Expressions of ABCA1 and LXRα mRNA and protein were detected by RT-PCR and Western blot respectively.Results The efflux rate of apoA-Ⅰ,cholesterol and cholesterol ester was significantly higher while the serum levels of cholesterol and cholesterol ester were significantly lower and the expression levels of ABCA1 and LXRα mRNA and protein were significantly higher in β3 AR agonist group than in control group.The serum levels of cholesterol and cholesterol ester were significantly higher while the efflux rate of cholesterol and cholesterol ester and the expression levels of ABCA1 and LXRα mRNA and protein were significantly lower in β3-AR antagonist groupt than in β3-AR agonist group (0.49±0.10 vs 1.24±0.02,0.85±0.05 vs 1.32±0.05,0.38±0.01 vs 1.45±0.20,0.08±0.01 vs 0.76±0.02,P＜0.01).Conclusion β3 AR promotes cholesterol efflux by upregulating the expression of apoA-Ⅰin HepG2 cells.
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Objective To investigate the effect of β3-adrenoreceptor (β3-AR)overexpression on cardiac hypertrophy. Method Sprague-Dawley rat neonatal ventricular cardiomyocytes (NRVMs) were isolated and cul-tured in vitro.The infection of lentiviruswas examined after cardiomyocytes were infected with lentivirus at differ-ent multiplicity of infection (MOI) of 20、50、80 and 100. Fluorescence microscopy was used to observe the ex-pression of GFP and to confirm the best MOI for lentivirus infection. Following the enforced expression of β3-AR by lentivirus, 2uM norepinephrine (NE) was used to treatment the infected cardiomyocytes for 48h. Expressions of β3-AR、c-myc and c-fos protein in cardiomyocytes were detected by Western Blot. Results The results of fluorescence microscopy indicated that the best MOI was 50. The protein level of β3-AR was significantly in-creased in β3-AR overexpression group compared with the control group and the NE treatment group (P < 0.05). Following the treatment of NE , the expressions of c-myc and c-fos were also significantly increased in β3-AR overexpression group compared with the control group (P < 0.05). Conclusion Over-expression of β3-AR can aggravate cardiomyocyte hypertrophy.
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Objective To evaluate the effects of the right stellate ganglion block on the expression of β3adrenoceptor (β3-AR) in rabbits with heart failure.Methods Forty-eight Japanese white rabbits of both sexes,weighing 2.5-3.0 kg,were randomly divided into 3 groups (n =16 each):sham operation group (group S),heart failure group (group HF) and right stellate ganglion block group (group RSGB).Heart failure was induced by occlusion of left anterior descending branch of coronary artery and confirmed by ultrasonic cardiography 4 weeks later.A PE-10 catheter was inserted into the right stellate ganglion for administration of drugs.0.25％ bupivacaine 2 ml was injected through the catheter once a day for 2 weeks in group RSGB,while the equal volume of normal saline was injected instead of bupivacaine in S and HF groups.The left ventricular end-diastolic diameter (LVEDD),left ventricular end-systolic diameter (LVESD),ejection fraction (EF) and left ventricular fractional shortening (LVFS) were measured at 1 day before ligation (T0),before catheter insertion (T1),before 8th administration (T2),and 1 day after the last administration (T3).Eight rabbits were sacrificed at T1 and T3 in each group and myocardial specimens were obtained from the apex of the left ventricle for determination of the expression of β3-AR by Western blot.Results Compared with group S,the LVEDD and LVESD were significantly enlarged and LVEF and LVFS were decreased at T1-3,and the expression of β3-AR was up-regulated at T1,3 in groups HF and RSGB (P ＜ 0.05).Compared with group HF,the LVEDD and LVESD were significantly decreased,LVEF and LVFS were increased,and the expression of β3-AR was significantly down-regulated at T3 in group RSGB (P ＜ 0.05).Conclusion The right stellate ganglion block can improve the cardiac function of rabbits with heart failure through down-regulating the expression of β3-AR in myocardium.
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Objective To investigate the relationship between Trp64Arg mutation in the β3-adrenergic receptor (β3-AR) gene and the incidence of hypertension in obese subjects. Methods A seven-year follow-up study was conducted in 377 simple obese subjects who had Trp64Arg mutation in the β3-AR gene and some clinical metabolic parameters, such as body mass index, waist circumference, waist-hip ratio, blood pressure, lipid profile, fasting blood glucose, fasting insulin and insulin resistance index (HOMA-IR) were measured in the year of 2000 and 2007. Results The results of follow-up indicated that the incidence of hypertension in Trp64Arg heterozygote subjects were higher than that in Trp64Trp homozygote subjects (52.7% ,69/131 vs 37.0% ,91/246,P < 0.01), the difference was only seen in male (59.5%, 50/84 vs 45.1%, 64/142, P < 0.05). The incidence of hypertension in both Trp64Trp homozygote and Trp64Arg heterozygote subjects were higher in obese male than those in obese female (P < 0.01 or <0.05). After seven years, the blood pressure increased (9.7 ± 4.3)/(5.4 ± 4.0) mm Hg(1 mm Hg = 0.133 kPa) in Trp64Trp homozygote,and (12.8 ± 5.2)/ (7.9 ± 4.7) mm Hg in Trp64Trp heterozygote subjects. Compared with that in Trp64Trp homozygote subjects, lipid profile, fasting insulin and HOMA-IR was increased significantly in Trp64Trp heterezygote subjects (P < 0.05). Logistic analysis showed that β3-AR gene mutation, male, central obesity and insulin resistance were associated with the incidence of hypertension in obese subjects. Conclusion The β3-AR gene Trp64Arg mutation is the independent risk factor in the incidence of hypertension in male.
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We sought to determine the effects of activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on multilocularization of adipocytes in adult white adipose tissue (WAT). Male C57BL/6 normal, db/db, and ob/ob mice were treated with agonists of PPAR-gamma, PPAR-alpha, or beta3-adrenoceptor for 3 weeks. To distinguish multilocular adipocytes from unilocular adipocytes, whole-mounted adipose tissues were co-immunostained for perilipin and collagen IV. PPAR-gamma activation with rosiglitazone or pioglitazone induced a profound change of unilocular adipocytes into smaller, multilocular adipocytes in adult WAT in a time-dependent, dose-dependent, and reversible manner. PPAR-alpha activation with fenofibrate did not affect the number of locules or remodeling. db/db and ob/ob obese mice exhibited less multilocularization in response to PPAR-gamma activation compared to normal mice. Nevertheless, all adipocytes activated by PPAR-gamma contained a single nucleus regardless of locule number. Multilocular adipocytes induced by PPAR-gamma activation contained substantially increased mitochondrial content and enhanced expression of uncoupling protein-1, PPAR-gamma coactivator-1-alpha , and perilipin. Taken together, PPAR-gamma activation induces profound multilocularization and enhanced mitochondrial biogenesis in the adipocytes of adult WAT. These changes may affect the overall function of WAT.
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Animals , Male , Mice , Adipocytes/cytology , Adipose Tissue, White/cytology , Cell Nucleus Division , Hypoglycemic Agents/pharmacology , Ion Channels/metabolism , Mice, Inbred C57BL , Mice, Obese , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , PPAR alpha/agonists , PPAR gamma/agonists , Phosphoproteins/metabolism , Receptors, Adrenergic, beta-3/agonists , Thiazolidinediones/pharmacology , Trans-Activators/metabolismABSTRACT
Objective To investigate the relationship between Trp64Arg mutation in β3-adrenerglc receptor (β3-AR) gene and the incidence of metabolic syndrome (MS). Methods A seven-year follow-up study was conducted in 386 simple obese subjects and 175 normal weight subjects in whom geno-typing of Trp64Arg mutation in β3-AR gene was examined in 2000. Results There were no differences between a Trp64Trp homozygote group and a Trp64Arg heterozygote group of whether obese or normal weight subjects with respect to adiposity, blood pressure, lipid profile, fasting blood glucose and fasting insulin in the baseline. The results of follow-up indicated that the incidence of MS in the Trp64Arg heterozygote group was higher than that in the Trp64Trp homozygote group of obese males (54. 76% vs 40. 85% ,P <0. 05) but not in the group of obese females. The incidences of MS both in the Trp64Trp homozygote group and Trp64Arg heterozygote group were higher in obese males than in obese females (40. 85% vs 18. 27% and 54. 76% vs 21.28% ,all P <0. 01 ) . No significant differences were found in incidences of MS both in the Trp64Trp homozygote group and Trp64Arg heterozygote group of normal weight subjects whether the comparison was made between males and females respectively or between males and females. The overall incidence of MS in the obese subjects were significantly increased than that in the normal weight subjects whether there was genevariant or not(31.30% vs 6. 03% and 42. 75% vs 12. 73%, all P <0. 01 ). Logistic analysis showed thatβ3-AR gene variant was associated with increased incidence of MS in males. Conclusion β3-AR gene Trp64Arg mutation is an independent risk factor for the incidence of MS in males.Conclusion β3-AR gene Trp64Arg mutation is an independent risk factor for the incidence of MS in males.
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Objective To explore the effects of the autoantibody against the second extracellular loop of ?3-adrenoceptor(?3AR)from children with heart failure on isolated cardiomyocytes of adult rats.Methods The synthetic peptide corresponding to the sequence of the se-cond extracellular loop(176-202 amino acid residues)of the human ?3AR was used as the antigen to screen the anti-?3AR autoantibodies from the sera of the 50 children with heart failure and 50 healthy children by enzyme linked immunosorbent assay(ELISA);IgG in the children with heart failure of positive autoantibodies sera was purified.The effects of purified IgG per each group on contractile response of isolated cardiomyocytes of adult rats were observed using motion-edge detection system and double-provocation fluorescence photomultiplier system.Results Among the 50 children with heart failure,the anti-?3AR autoantibodies positive rate was 30%(15/50 cases),and ob-viously higher than that of healthy children[12%(6/50)cases,P