Abstract
The beta3-adrenergic receptor (β3AR) has a significant function on controlling energy expenditure at the whole body level. Trp64Arg polymorphisms of β3AR gene (β3AR-Trp64Arg) have been first reported to be associated with obesity and related traits. Obesity is associated with a broad range of complications, from cardiovascular disease to knee osteoarthritis, to name a few. Several types of cancer, i.e. cancer of colon, breast, endometrium, kidney and oesophagus, are also recognized as one of the obesity-associated disorders. 1 Besides colon cancer, 2 we consider that gall bladder cancer may be a β3AR-Trp64Arg-related cancer, as β3AR-Trp64Arg is reportedly associated with gallstone formation. 3 Thus, we agree with Kapoor's opinion that β3AR-Trp64Arg can be closely linked with systemic disorders of metabolism. 2
Factors that disclose the linkage between β3AR-Trp64Arg and systemic metabolic disorders can be insulin resistance and the ensuing hyperinsulinaemia, 4,5 as well as increased levels of growth factors and changed levels of adipocyte-derived cytokines/hormones such as adiponectin. The possible influence of β3AR-Trp64Arg on dietary intake behaviour would also be relevant to the development of insulin resistance and long-term exposures of harmful molecules including reactive oxygen intermediates. 6,7 In considering the difference in autonomic nerve system activity of β3AR-Trp64Arg, 8 further research on the effects of immunomodulation through autonomic nerve system on various diseases including cancer 9 is required.
Because the recent increases in the incidence of obesity and related disorders are explained by the roles of β3AR-Trp64Arg as one of the thrifty gene polymorphisms, 10 more increases in the incidence of several other metabolic diseases including cancer are expected. On the other hand, knowledge of the association between β3AR-Trp64Arg and systemic metabolic disorders implies the presence of modifiable pathophysiology mechanisms such as insulin resistance. Namely, anti-obesity approaches involving modification of lifestyle (e.g. nutrition, physical activity) and drugs for improvement of insulin resistance may be beneficial not only on obesity but on additional disorders including cancer as well. Future studies on the role of β3AR-Trp64Arg in a range of diseases are warranted to understand better the association and establish prevention strategies to alter the progression of systemic metabolic disorders.