Kazuko Masuo, Hiromi Rakugi and Toshio Ogihara Pages 118 - 129 ( 12 )
Obesity, hypertension, diabetes mellitus (especially type 2 diabetes mellitus) and metabolic syndrome are rapidly growing public health problems. Heightened sympathetic nerve activity is a well-established observation in obesity, hypertension and diabetes mellitus. Human obesity, hypertension and diabetes have strong genetic as well as environmental determinants. Reduced energy expenditure and resting metabolic rate are predictive of weight gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The thermogenic effects of catecholamines in obesity have been mainly mediated via the β2 and β3-adrenergic receptors in humans. Further, β2-adrenoceptors importantly influence vascular reactivity and may regulate blood pressure. Genetic polymorphisms of the β-adrenoceptor gene have been shown to alter the function of several adrenoceptor subtype and thus to modify the response to catecholamine. Among β2-adrenoceptor polymorphisms, Arg16Gly, Gln27Glu, and Thr164Ile are considered the most functionally important. β2-adrenoceptor genes have been studied in relation to obesity. Genetic variations in the β3-adrenoceptor, such as the Try64Arg variant, are also associated with both obesity and hypertension. However, the precise relationships of the polymorphisms of β2- and β3-adrenoceptor genes with sympathetic nervous system activity, obesity, hypertension and metabolic syndrome have not been fully clarified. A few studies regarding the relationships between sympathetic nervous activity and adrenoceptor polymorphisms in the same studies have been reported. Masuo et al. have observed in a series of studies in a Japanese male cohort that: 1) β2-adrenoceptor polymorphisms are associated with heightened sympathetic nerve activity, and predict the future onset of obesity and hypertension in nonobese individuals, 2) β2-adrenoceptor polymorphisms accompanied by heightened sympathetic nerve activity and abdominal obesity, predict weight loss resistance during a weight loss program, and also predict rebound weight gain, 3) β2-adrenoceptor polymorphisms are linked to blunted leptin-mediated sympathetic nerve activation, leptin-resistance and resultant obesity, 4) β2-adrenoceptor polymorphisms are related to insulin-resistance, in both nonobese and obese normotensive individuals, and 5) β3-adrenoceptor polymorphism is directly linked to obesity and hypertension, but only in obese individuals. These suggest that β2- and β3-adrenoceptor polymorphisms accompanying heightened sympathetic nerve activity play a major role in the onset and the maintenance of obesity, hypertension and insulin resistance. This article provides the current topics involving the influence of the sympathetic nervous system and β2- and β3-adrenoceptor polymorphisms in obesity, hypertension and metabolic syndrome (type 2 diabetes).
Beta2-adrenoceptor polymorphisms, beta3-adrenoceptor polymorphisms, sympathetic nervous system activity, obesity, hypertension, type 2 diabetes mellitus, metabolic syndrome
Nucleus Network Ltd. and Human Neurotransmitter Laboratory, Baker IDI Heart and Diabetes Research Institute, 89 Commercial Road, Melbourne, Victoria 3004, Australia.