Research progress of beta3-adrenergic receptor in heart / 中国小儿急救医学

The expression of beta3-adrenergic receptor(β3-AR) is very low in the physiological state of the heart, but increases in the pathological state of heart failure.Due to the negative inotropic effect when stimulating β3-AR, the early researchers believed that the increase of β3-AR in the pathological state would aggravate the cardiac function, but the later researches of beta3-AR on heart failure found a contrary conclusion.More and more evidence suggests that beta3-AR may play a useful role in the cardiovascular system, which making beta3-AR to be a new target for the treatment of cardiovascular disease.This article reviewed the progress of the above researches.

Medium-Chain Triglyceride Activated Brown Adipose Tissue and Induced Reduction of Fat Mass in C57BL/6J Mice Fed High-fat Diet / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate activation of brown adipose tissue (BAT) stimulated by medium-chain triglyceride (MCT).</p><p><b>METHODS</b>30 Male C57BL/6J obese mice induced by fed high fat diet (HFD) were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride (LCT) respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue (IBAT) mass, expressions of mRNA and protein of beta 3-adrenergic receptors (β3-AR), uncoupling protein-1 (UCP1), hormone sensitive lipase (HSL), protein kinase A (PKA), and adipose triglyceride lipase (ATGL) in IBAT were measured.</p><p><b>RESULTS</b>Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group (P<0.05) after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group (P<0.05). Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein of β3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group (P<0.05).</p><p><b>CONCLUSION</b>Our results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.</p>

Association Analyses of beta3AR Trp64Arg and UCP-2 -866G/A Polymorphisms with Body Mass Index in Korean / 영남의대학술지

BACKGROUND: Obesity is the most common nutritional disorder in Western society as well as in Korea. Obesity results from a combination of genetic, environmental, and behavioral factors. MATERIALS AND METHODS: In an attempt to investigate the association of obesity with its candidate genes, beta3 adrenergic receptor (beta3AR) and uncoupling protein 2 (UCP2), we analyzed polymorphisms of beta3AR Trp64Arg and UCP2 -866G/A by PCR-RFLP analysis and the obesity-related phenotypes, including body mass index (BMI), fasting glucose concentration, and plasma lipid profiles in 750 subjects. RESULTS: The Trp64Arg polymorphism in the beta3AR gene was not statistically associated with the BMI. The UCP2 -866G/A polymorphism was significantly higher in obese than in non-obese subjects (P<0.05). However, the UCP2 -866A/A polymorphism was higher in the non-obese subjects. CONCLUSION: These results suggest that the UCP2 -866G/A polymorphism might be more useful for the prediction of obesity and obesity-associated diseases in Korean patients than the beta3AR Trp64Arg polymorphism.

Association of Polymorphism in beta3-Adrenergic Receptor Gene with Fat Distribution / 대한내분비학회지

BACKGROUND: Reasons for obesity include environmental factors and, more largely so, genetic factors. There have been many studies on these genetic factors. So far, genes related to obesity such as Leptin, Uncoupling Protein(UCP), Peroxisome proliferator activated receptor-gamma(PPAR-gamma), and Beta3-adrener-gic receptor(beta3-AR) gene have been discovered. Among these, beta3-AR is expressed in visceral adipose tissue and is thought to contribute to the regulation of resting metabolic rate and lipolysis. The missense mutation of beta3-AR gene, resulting in replacement of tryptophan by arginine at position 64(Trp64Arg), is associated with decreased resting metabolic rate and weightgain. We performed this study to determine if Trp64Arg polymorphism of beta3-AR gene is associatedwith obesity in Koreans. METHOD: We investigated the relationship between the beta3-AR gene mutation and body mass index (BMI), waist circumference, hip circumference, waist to hip ratio(WHR), area of subcutaneous fat, area of visceral fat, visceral to subcutaneous fat ratio(VSR), and lipid profile. 198 subjects were included in this study of which 97 were of normal weight and 101 were obese. Anthropometric data was obtained from physical examination and medical records. RESULT: In the cases of beta3-AR gene mutation of the obese group, the ratio of Trp/Arg and Arg/Arg are 43% and 5%, respectively, which were higher than the normal group(36%, 1%), although a statistical significant was not found. There was significant difference in the are of subcutaneous fat. Normal group(Trp/Trp) measured at 213.9+/-109.6cm2 versus 244.0+/-127.7cm2 (Trp/Arg) and 323.9+/-189.9cm2(Arg/Arg) for the mutation groups. Circumference of waist, circumference of hip, WHR, area of visceral fat, and VSR were higher in the mutation groups than in normal subject, but not significantly different. CONCLUSION: These results suggest that a genetic mutation in the beta3-AR gene can affect body fat composition, and is associated with obesity in Korean adults.

Associations of Polymorphisms in Uncoupling Protein 2 and 3-Adrenergic Receptor with Obesity in Korean Adults / 대한내분비학회지

BACKGROUND: The genetic and environmental factors involved in the development of obesity and several candidate genes have been suggested to have an influence on energy and fuel metabolism. However, the specific genetic defects responsible for human obesity have not been identified yet. It is likely that a combination of polymorphisms in one or more candidate genes may affect energy metabolism and the development of obesity. We performed this study to determine the role of 45 bp insertion in the uncoupling protein (UCP)2 exon 8 and Trp64Arg polymorphism of beta3-adrenergic receptor ( 3-AR) gene in the regulation of body weight and the pattern of fat distribution. METHODS: In 114 subjects (male: 40, female: 74, mean body mass index: 24.1+/-2.7 kg/m2, 80 subjects with normal glucose tolerance, 34 subjects with impaired glucose tolerance), body fat distribution patterns were assessed by anthropometric measurement, bioelectric impedance analysis and computed tomogram. The genotypes of UCP genes were determined by polymerase chain reaction (PCR), and mutation in 3-AR gene by PCR followed by enzymatic digestion. RESULTS: In UCP2 genes, the frequency of deletion homozygote (DD) was 59.4%, heterozygote (DI) was 3.5% and insertion homozygote (II) was 3.1% Meanwhile, in 3-AR, the frequency of TrpTrp was 67.9%, TrpArg was 29.5% and ArgArg was 2.7%. In the lean group (subjects with a BMI less than 25 kg/m2), the frequencies of insertion allele and Arg64 allele were not significantly different than those among the overweight subjects (BMI > or = 25 kg/m2). There was not significant difference in clinical, biochemical or body fat distribution patterns between the groups according to UCP2 polymorphism. In the case of the polymorphism in 3-AR gene, the subjects with ArgArg homozygotes had lower HDL-cholesterol level (p<0.05). For the individuals over 40 years of age, BMI was greater among those with the deletion homozygotes and Arg64 allele, as compared to other groups according to the combination of UCP2 and 3-AR genotypes (p<0.05). CONCLUSION: These results suggest that genetic variations in UCP2 and 3-AR can synergistically affect metabolic rate and susceptibility to weight gain, thereby and contribute to the change in body weight in later life.

Relation of beta 3-Adrenergic Receptor Gene Polymorphism to the Patterns of Body Fat Distribution and Insulin Sensitivity in Female Nondiabetic Offspring of Patients with NIDDM / 대한내분비학회지

BACKGROUND: Obesity is an important metabolic abnormality as a pathogenesis of non-insulin dependent diabetes mellitus(NIDDM), and genetic factors have been suggested to be involved in the development of obesity and NIDDM. beta 3-adrenergic receptor gene polymorphism has been reported to be related to an earlier onset of NIDDM and increased capacity of weight gain in obesity. The purpose of this study was to investigate the relation of beta 3-adrenergic receptor gene polymorphism to body fat distribution pattern and insulin resistance in female nondiabetic offpsring of patients with NIDDM. METHODS: We assessed the patterns of body fat distribution by anthropometric measurement, bioelectric impedence analysis and computed tomogram; insulin sensitivity by using frequently sampled intravenous glucose tolerance test and the minimal model analysis. We inverstigated the beta 3 -adrenergic receptor gene polymorphism by PCR and RFLP. RESULTS: 1) The frequency of beta 3 adrenergic receptor gene polymorphism was as follows; wild type (Trp64Trp) 69.8%, Trp64Arg heterozygote 26.4%, Arg64Arg homozygote 3.8% in the offspring of patients with NIDDM. According to obesity, there was no significant difference of distribution of Arg64 allele between nonbese and obese subjects. 2) In the mutant subjects with Arg64 allele, the concentrations of total and LDL cholesterol were significantly increased (p<0.01), but fasting serum glucose and insulin, percent body fat, visceral fat area and visceral to subcutaneous fat area ratio were insignificantly increased, SI were insiginificantly decreased. 3) Multiple regression analysis showed that Arg64 allele did not significantly associated with visceral obesity and insulin resistance. CONCLUSION: The beta 3-adrenergic receptor gene polymorphism was related to dyslipidemia, but not related to visceral adiposity or insulin resistance in nondiabetic offspring women of patients with NIDDM. Further prospective studies in these subjects will be needed for the clarification of pathogenetic role of beta 3-adrenergic receptor gene polymorphism in the development of insulin resistance and NIDDM.