A mutation of the b3-adrenergic receptor is associated with visceral obesity but decreased serum triglyceride

Abstract

The sympathetic nervous system plays a major role in energy expenditure. By catecholamine stimulation, lipolysis in white adipose tissue and thermogenesis in brown adipose tissue and skeletal muscle are induced. These effects are mediated by several subtypes of catecholamine receptors namely Summary The Trp64Arg mutation of the b 3-adrenergic receptor (b3AR) is prevalent in several ethnic groups and is associated with weight gain, and some features of syndrome X such as insulin resistance and dyslipidaemia. Nevertheless, it is not known at present whether this mutation is associated with visceral obesity, which is an important risk factor for the development of hypertension, dyslipidaemia, insulin resistance, non-insulin-dependent diabetes mellitus, and atherosclerosis. To investigate whether this mutation may contribute to visceral obesity, we studied the relationships between b 3AR genotypes and clinical phenotypes. The Trp64Arg allele of b 3AR was examined in 278 Japanese men with respect to variables relating to visceral obesity assessed by computerised tomography. To detect the Trp64Arg mutation, polymerase chain reaction-restriction fragment length polymorphism analysis using Bst NI digestion was performed. This mutation was more frequently observed in subjects with higher body mass index (BMI) (p = 0.02). Moreover, in 120 subjects with a moderate degree of obesity (222 ), the mutation (homozygotes and heterozygotes) was associated with visceral obesity (higher ratio of visceral to subcutaneous fat area; V/S) (p = 0.03). Furthermore, the Trp64Arg allele was more frequent in subjects with lower serum triglyceride levels (p = 0.02) and the Trp64Arg homozygotes, but not heterozygotes, exhibited lower triglyceride levels. Thus, this mutation appears to be associated with visceral obesity but with lower serum triglyceride. It is suggested that those with the mutation may describe a subset of subjects characterized by decreased lipolysis in visceral adipose tissue. [Diabetologia (1997) 3-adrenergic receptor; W/H ratio, waist/hip ratio; V/S ratio, visceral to subcutaneous fat ratio; NIDDM, non-insulin-dependent diabetes mellitus; CT, computer tomography.

The Trp64Arg polymorphism of the β3-adrenergic receptor gene and obesity in Chinese subjects with components of the metabolic syndrome

“…The relationship between this mutation and BMI has been reported in Chinese type 2 diabetics 27 and other major ethnic groups, including Caucasians, 31,32 Blacks 14 and Japanese, 9,15 in which the reported genotype frequencies are similar to those in our study. The dosedependent relationship between the A allele and the anthropometric markers, as well as the maintenance of this relationship in nearly all the subgroups included in these analyses, supports a contributory role for this polymorphism or a closely linked genetic factor in the modulation of obesity.…”

“…27 Furthermore, other groups have reported similar associations between this polymorphism and obesity in Japanese populations. 9,15 In addition to obesity, we found evidence to support the involvement of this gene polymorphism in modulating lipid pro®les with the A allele being associated with reduced fasting plasma HDL-cholesterol levels. A relationship between this polymorphism and lipid metabolism has been reported in a Japanese population, but in association with decreased serum triglyceride concentrations.…”

“…A relationship between this polymorphism and lipid metabolism has been reported in a Japanese population, but in association with decreased serum triglyceride concentrations. 15 However, their work does support our ®ndings associating the A allele with increased obesity, in particular with visceral obesity as de®ned by computerized tomography scanning at the level of the umbilicus. Their conclusions rely only on the difference between the homozygote genotypes, of which there were only nine AA homozygotes, because the AT heterozygotes had similar triglyceride levels to those with the TT genotype.…”

Obesity and polymorphisms in genes regulating human adipose tissue

“…[62][63][64] A non-synonymous polymorphism, Trp64Arg, in ADRB3 has been reported to be associated with weight gain among obese in a cohort of morbidly obese and non-obese French, and in some studies with obesity. [65][66][67][68][69][70] Furthermore, Trp64Arg has been associated with reduced basal metabolic rate and decreased lipolytic sensitivity to an ADRB3-specific ligand, which could explain an impact on adiposity. 65,66,70,71 In the ADRB1 gene, the Gly389Arg 389Arg allele, which affects coupling of the receptor to downstream targets, has been associated with obesity.…”

Effect of β3-adrenergic receptor gene polymorphism on body weight change in middle-aged, overweight women

“…The β 3 -AR gene polymorphism of the human β 3 -AR gene, characterized by the substitution of arginine for tryptophan at position 64 (64Arg allele), has been reported to be positively associated with body weight (BW) gain (8,9), obesity (10,11), and obesity-related metabolic syndrome (12)(13)(14). However, there are also reports that showed no significant correlation of the 64Arg allele with BW gain and metabolic disorders (15)(16)(17)(18).…”