The adrenergic system plays a key role in regulating energy balance through the stimulation of both thermogenesis and lipid mobilization in brown and white adipose tissues in human and various animal models. Recent studies have suggested that a missense Trp64Arg mutation in the ß3 adrenergic receptor(ß3-AR) gene was involved in obesity, insulin resistance, decreased energy expenditure, and earlier onset of non-insulin dependent diabetes in different ethnic groups. In the mature adipose cells, ß3-AR is major adrenoreceptor which stimulates uncoupling pretein(UCP) by a cAMP metabolic pathway. UCP is a mitochondrial component specifically expressed in brown adipose tissue where it is involved in thermogenesis. Recently, a UCP gene variant of Bcl Ⅰ restriction polymorphism has been associated with an increased propensity to gain weight over time. We have investigated, using a PCR-RFLP assay, whether the genetic polymorphisms of ß3-AR and UCP were associated with differences of weight loss in obese patients submitted to an obese control program which included a period of fasting. Body weight and body mass index were measured at baseline and after a period of fasting and serum lipids, glucose, and insulin levels, and blood pressure were also determined in 40 obese patients. For ß3-AR and UCP polymorphisms, two alleles of ß3-AR, Trp64 and Arg64 alleles were identified with respective frequencies of 0.725 and 0.275 and two alleles of UCP, allele 1 and 2 were identified with respective frequencies of 0.375 and 0.625. No associations were found between these mutations and body mass index, body fat, and various diabetes and cardiovascular risk factors. No difference in weight loss was found according to ß3-AR Trp64Arg mutation and UCP polymorphism. These findings do not support the view that the Trp64A mutation in the ß3-AR or a genetic variant of the UCP gene is determinant for the expectation of weight loss after obesity control program.

Keywords: ß3-adrenergic receptor, Uncoupling protein, Polymorphism, Obesity