fl-Adrenergic Stimulation and Abdominal Subcutaneous Fat Blood Flow in Lean, Obese, and Reduced-Obese Subjects E.E. Blaak, M.A. van Baak, G.J. Kemerink, M.T.W. Pakbiers, G.A.K. Heidendal, and W.H.M. Saris The present study was designed to investigate whether the ~-adrenergically mediated blood flow response of abdominal subcutaneous adipose tissue (per unit adipose tissue weight) was altered in obesity and to study the effect of weight reduction on this response. Body composition (underwater weighing) and fat blood flow were determined in a group of lean (n = 9; % body fat, 11.6 -+ 3.9) and obese (n = 9; % body fat, 28.3 -+ 1.8) subjects, In seven obese subjects, measurements were also performed after a 4-week period of weight reduction induced by a very-low-calorie diet (% body fat after diet 23.4 __.3.3). After an overnight fast, abdominal subcutaneous fat blood flow was determined by the 133xenon washout technique during a 3g-minute period of supine rest and during 30-minute periods of infusion of the ~-agonist isoprenaline (ISO) with and without simultaneous infusion of the ~1-blocker atenolol (AT). Basal abdominal fat blood flow was significantly higher in lean as compared with obese subjects, whereas weight reduction significantly increased basal fat blood flow (obese v reduced-obese, P < .05). There was a significant increase in abdominal fat blood flow as a result of ISO infusion in lean and obese subjects before and after weight reduction. During ISO + AT infusion, abdominal fat blood flow was still significantly increased as compared with control values in lean and obese subjects. The increase in blood flow during ISO was significantly higher in lean subjects than in obese subjects, whereas the ISO + AT-induced blood flow response was comparable. These data suggest that especially the ~1-mediated blood flow response is blunted in obese subjects. Although the increase in the ISO-induced blood flow response was not significantly different after as compared with before the diet, there was a significant positive relationship between the decrease in percent body fat and the change in the ISO-mediated abdominal blood flow as a result of weight loss (P < .05), In conclusion, the present study shows that the ~-adrenergically mediated abdominal fat blood flow response (expressed per unit weight) is diminished in obesity. This decreased blood flow response tended to change in a direction toward the condition seen in lean subjects after partial weight reduction. Copyright © 1995 by W.B. Saunders Company DIPOSE TISSUE blood flow may play an important role in adipose tissue metabolism by delivering sub- strates, lipolytic hormones, and carrier proteins, respon- sible for the transport of fatty acids in the bloodstream, to the tissue. 1-3 Since triglyceride synthesis and the mobiliza- tion of fatty acids are the principal events in adipose tissue, the relationship between adipose tissue blood flow and net lipolysis is of special interest. By means of the 133xenon clearance technique, it has been shown that in several metabolic situations characterized by an increased mobiliza- tion of the fat stores, such as fasting, 4 exercise, 5 or infusion of epinephrine, 6 adipose tissue blood flow is increased. Previous studies have shown that adipose tissue blood flow (per unit adipose tissue weight) may be decreased in obesity. 4,7,8 In addition, a blunted abdominal adipose tissue blood flow response to glucose ingestion has been reported in obese subjects. 7 In previous studies we found that the lipolytic response as a result of infusion of the [31- and [32-agonist isoprenaline (ISO) is lower in obese subjects than in lean subjects, as reflected by lower ISO-induced increases in arterial fatty acid and glycerol levels. 9 This may favor the maintenance (and perhaps development) of large fat stores. The impaired lipolytic response in obesity may be associated with a decreased blood flow per unit adipose tissue weight, since a diminished blood flow response may affect the delivery of ISO and transport proteins for fatty acids to adipose tissue. 1,3 In addition, a model has been proposed that raises the possibility that the release and reuptake of fatty acids by adipocytes within adipose tissue may be controlled by adipose tissue perfusion, z The present study was designed to investigate whether the adipose tissue blood flow response as a result of [3-adrenergic stimulation was altered in obesity and to study the effect of weight reduction on this response. SUBJECTS AND METHODS In this study, abdominal subcutaneous fat blood flow was determined in lean (n = 9) and obese (n = 9) men recruited by an advertisement in the local newspaper. In seven obese subjects, measurements were also performed after weight reduction (n = 7, reduced-obese subjects). All subjects were outpatients throughout the study. Physical characteristics are indicated in Table 1. The subjects were medically screened by a questionnaire and physical examination. All subjects had normal glucose tolerance and had no or only very mild hypertension (diastolic blood pressure < 95 mm Hg). None were taking medication or had clinical evidence of illness apart from obesity. The study protocol was reviewed and approved by the Ethics Committee of the University of Limburg, and all volunteers provided written consent. The study protocol consisted of two experiments with 1 week in between. In the first experiment the 13-agonistISO was infused in increasing standard- ized doses, and during each infusion period plasma concentrations of ISO were determined (ISO infusion test). In the second experiment, abdominal subcutaneous adipose tissue blood flow was studied during ISO infusion with and without infusion of the 131-blockeratenolol ([AT] blood flow measurement). To reduce the variability in the blood flow experiment, the dose of ISO in this experiment was individually determined and was the dose that increased plasma ISO to a fixed value of 165 pg/mL. The two experiments above were repeated after weight reduction when the subjects had been weight-stable for at least 4 to 5 days. During the experiments, room temperature was kept between 21° and 23°C. From the Department of Human Biology, University of Limburg, Maastricht; and the Departments of Nuclear Medicine and Radiology, University Hospital Maastricht, Maastricht, The Netherlands. Submitted November 16, 1993; accepted May 12, 1994. Address reprint requests to E.E. Blaak, PhD, Department of Human Biology, University of Limburg, PO Box 616, 6200 MD Maastricht, The Netherlands. Copyright © 1995 by W.B. Saunders Company 0026-0495/95/4402-0009503.00/0 Metabolism, Vol 44, No 2 (February),1995: pp 183-187 183