E. Blaak

β-adrenergic stimulation and abdominal subcutaneous fat blood flow in lean, obese, and reduced-obese subjects

The present study was designed to investigate whether the beta-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 30-minute period of supine rest and during 30-minute periods of infusion of the beta-agonist isoprenaline (ISO) with and without simultaneous infusion of the beta 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II: a hormone that affects lipid metabolism in adipose tissue.

Background:Alterations in adipose tissue lipolysis may contribute to the pathophysiology of obesity and insulin resistance. We examined the effects of angiotensin II (Ang II) on abdominal subcutaneous adipose tissue lipolysis in humans.Methods and results:First, adipocytes obtained from nine normal weight and seven obese subjects were stimulated with Ang II (10−14–10−6u2009M). Glycerol concentration in the medium, used as an indicator of adipocyte lipolysis, was significantly reduced (∼20%) after Ang II stimulation in adipocytes from normal weight (P=0.04) and obese subjects (P<0.001). Based on these observations, adipocytes of seven additional obese subjects were stimulated with lower doses of Ang II (10−17–10−6u2009M) in the presence and absence of Ang II type 1 (AT1) receptor blockade. Lipolysis was dose dependently inhibited by ∼20 to 25% after Ang II stimulation (P=0.001). AT1 receptor blockade completely abolished the Ang II-induced effects (P=0.35).Conclusion:Ang II directly inhibits abdominal subcutaneous adipocyte lipolysis in normal weight and obese subjects via the AT1 receptor.

β-Adrenergically mediated thermogenic and heart rate responses: Effect of obesity and weight loss

β-Adrenergically mediated thermogenic and heart rate (HR) responses, as assessed by stepwise intravenous infusion of the β-agonist isoprenaline (ISO), were evaluated by partial regression analysis in a group of men with a wide range of body fat (n = 30) and in a subgroup of 16 obese men after weight loss. β-Adrenergically mediated thermogenesis (open-circuit ventilated-hood system) was blunted in obese subjects, as reflected by a significant positive correlation between percent body fat (hydrostatic weighing) and the plasma ISO concentration needed to increase resting energy expenditure (EE) by 15% (P < .001). The magnitude of the β-adrenergically mediated HR response was (negatively) associated with the basal plasma norepinephrine (NE) concentration (P < .001). Weight reduction resulted in a significant increase in thermogenic and HR responses in obese subjects. Furthermore, the increase in thermogenic response as a result of weight loss was negatively related to the magnitude of thermogenic response (P < .01) and positively related to the initial percent body fat (P < .05). The increase in HR response as a result of weight loss was positively related to the decrease in basal NE (P < .01) and the change in percent body fat (P < .05). In conclusion, the degree of adiposity was shown to be negatively related to the magnitude of β-adrenergically mediated thermogenesis, whereas the HR response was merely related to basal NE. Since weight loss resulted in a significant increase in the thermogenic response, the blunted β-adrenergically mediated thermogenesis does not seem to be a primary factor contributing to the development of obesity.

Lipolytic and nutritive blood flow response to beta-adrenoceptor stimulation in situ in subcutaneous abdominal adipose tissue in obese men

OBJECTIVE: β-Adrenoceptor-mediated whole-body lipolysis is impaired in obesity. This study investigated whether local adipocyte β-adrenergic sensitivity and changes in nutritive blood flow in subcutaneous abdominal adipose tissue contribute to this impaired response.METHODS: Three microdialysis probes were placed in the subcutaneous abdominal adipose tissue of eight obese and nine lean men. Each probe was perfused with either 0.1, 1 and 10u2009μM isoprenaline; 1, 10 and 100u2009μM dobutamine or 1, 10 and 100u2009μM salbutamol, each dose for 45u2009min.RESULTS: At baseline, interstitial glycerol concentrations and ethanol out/in ratios were comparable between groups. During nonselective β-, β1- and β2-adrenergic stimulation, interstitial glycerol concentrations increased and ethanol out/in ratios decreased similarly in obese and lean men.CONCLUSION: The lipolytic and nutritive blood flow response to β1- β2- and nonselective β-adrenergic stimulation in situ is comparable in lean and obese male subjects. The present data suggest that a blunted β-adrenergic sensitivity of the fat cell and an impaired local nutritive blood flow response do not contribute to the previously reported diminished whole-body β-adrenoceptor-mediated lipolytic response in obese males.