Abstract-No agreement exists as to the mechanisms responsible for the sympathetic hyperactivity characterizing human obesity, which has been ascribed recently to a chemoreflex stimulation brought about by obstructive sleep apnea rather than to an increase in body weight, per se. In 86 middle-age normotensive subjects classified according to body mass index, waist-to-hip ratio, and apnea/hypopnea index (overnight polysomnographic evaluation) as lean and obese subjects without or with obstructive sleep apnea, we assessed via microneurography muscle sympathetic nerve traffic. The 4 groups were matched for age, gender, and blood pressure values, the 2 obese groups with and without obstructive sleep apnea showing a similar increase in body mass index (32.4 versus 32.0 kg/m 2 , respectively) and waist-to-hip ratio (0.96 versus 0.95, respectively) compared with the 2 lean groups with or without obstructive sleep apnea (body mass index 24.3 versus 23.8 kg/m 2 and waist-to-hip ratio 0.77 versus 0.76, respectively; PϽ0.01). Compared with the nonobstructive sleep apnea lean group, muscle sympathetic nerve activity showed a similar increase in the obstructive sleep apnea lean group and in the nonobstructive sleep apnea obese group (60.4Ϯ2.3 and 59.3Ϯ2.0 versus 40.9Ϯ1.8 bs/100 hb, respectively; PϽ0.01), a further increase being detected in obstructive sleep apnea subjects (73.1Ϯ2.5 bursts/100 heart beats; PϽ0.01). Our data demonstrate that the sympathetic activation of obesity occurs independently in obstructive sleep apnea. They also show that this condition exerts sympathostimulating effects independent of body weight, and that the obstructive sleep apnea-dependent and -independent sympathostimulation contribute to the overall adrenergic activation of the obese state. Key Words: sleep apnea syndromes Ⅲ sympathetic nervous system Ⅲ chemoreceptors Ⅲ baroreflex S ubjects with obesity are characterized by an increase in urinary norepinephrine (NE), plasma levels of NE, efferent postganglionic muscle sympathetic nerve activity (MSNA), and renal NE spillover rate, 1-10 thereby displaying a hyperadrenergic state. This has been ascribed primarily to the insulin-resistance state and the subsequent hyperinsulinemia that occurs more frequently with an increase in body weight because in animals and human, insulin has been shown to stimulate the sympathetic nervous system. [11][12][13][14][15] However, it has also been ascribed to other mechanisms, among which is the chemoreceptor stimulation brought about by obstructive sleep apnea (OSA), 16,17 a condition that is also common in obese individuals. 18 Indeed, OSA has been reported to be the necessary condition for the obesity-related sympathetic hyperactivity to occur in a study by Narkiewicz et al 19 in which an increased number of sympathetic bursts to skeletal muscle tissues was seen only when obesity and OSA were concomitantly present.The present study was conducted to determine the relative contribution of the increased body weight, per se, versus OSA in producing the sympathetic ...