Failure to increase postprandial blood flow in subcutaneous adipose tissue is associated with tissue resistance to adrenergic stimulation

被引:17
作者
Ardilouze, J. -L. [1 ,2 ]
Sotornik, R. [1 ]
Dennis, L. A. [3 ]
Fielding, B. A. [3 ]
Frayn, K. N. [3 ]
Karpe, F. [3 ]
机构
[1] Univ Sherbrooke, Dept Med, Div Endocrinol, Sherbrooke, PQ J1H 5N4, Canada
[2] CHU Sherbrooke, Ctr Rech Clin Etienne Le Bel, Sherbrooke, PQ J1H 5N4, Canada
[3] Univ Oxford, Nuffield Dept Clin Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England
基金
加拿大健康研究院; 英国惠康基金;
关键词
Sympathetic nervous system; Adipose tissue; Blood flow; Insulin resistance; MONW; COMMON POLYMORPHISMS; INSULIN SENSITIVITY; METABOLICALLY-OBESE; NITRIC-OXIDE; RECEPTOR; GLUCOSE; BRAIN; DESENSITIZATION; RESPONSES; LIPOLYSIS;
D O I
10.1016/j.diabet.2011.06.005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims. - Adequate adipose tissue blood flow (ATBF) is essential for its metabolic and endocrine functions. From a metabolic point of view, sufficient increases in ATBF after meals permits full storage of excess energy into fat, thus protecting other tissues against the toxic effects of fatty acids and glucose spillover. It was previously shown that postprandial increases in ATBF are blunted in obese and insulin-resistant subjects, and that much of the postprandial ATBF response is the result of beta-adrenergic activation. Examination of previously recorded data on postprandial ATBF responses revealed an underlying heterogeneity, with postprandial ATBF being largely unresponsive to food stimuli in a substantial proportion of normal weight healthy people (low responders). Our study tests the hypothesis that this unresponsive pattern is due to resistance to beta-adrenergic stimulation in adipose tissue. Methods. - Five responders and five low responders were selected from a previously studied cohort and matched for BMI (20.5 +/- 0.7 vs 22 +/- 1 kg/m(2), respectively), gender (male/female: 2/3) and age (30 +/- 3 vs 37 +/- 6 years). Subcutaneous adipose tissue microinfusions of stepwise increasing doses of isoproterenol were performed with concomitant monitoring of blood flow, using the (133)Xenon washout technique. Results. - Although BMI was similar between responders and low responders, there were significant differences in fat mass (9.9 +/- 1.6 vs 14.4 +/- 1.6 kg; P < 0.05) and four-point skinfold thickness (33 +/- 4 vs 52 +/- 16 mm; P < 0.05). Lack of ATBF response to oral glucose was confirmed in the low responder group. In responders, ATBF was higher at baseline (5.4 +/- 1 vs 3.4 +/- 1 mL/min/100 g of tissue) and responded more distinctly to increasing isoproterenol doses (10(-8) M: 7.6 +/- 1.4 vs 4.9 +/- 1; 10(-6) M: 12.5 +/- 1.7 vs 7.5 +/- 1.6; and 10(-4) M: 20 +/- 1.7 vs 9 +/- 0.9 mL/min/100 g of tissue). Conclusion. - These data suggest that the lack of glucose-stimulated ATBF is associated with resistance to sympathetic activation in adipose tissue. (C) 2011 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:27 / 33
页数:7
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