Adaptative Nitric Oxide Overproduction in Perivascular Adipose Tissue during Early Diet-Induced Obesity
Adaptative Nitric Oxide Overproduction in Perivascular Adipose Tissue during Early Diet-Induced Obesity
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DOI：
10.1210/en.2009-1464
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发表时间：
2010-07-01
期刊：
影响因子：
4.8
通讯作者：
Somoza, Beatriz
中科院分区：
文献类型：
--
作者：
Gil-Ortega, Marta;Stucchi, Paula;Somoza, Beatriz
血管周围脂肪组织（PVAT）在调节血管张力中起着旁分泌作用。我们假设PVAT在饮食诱导的肥胖（DIO）的初始步骤中经历了适应性机制，这有助于保护血管功能。将4周龄雄性C57 BL/6 J小鼠分配至对照组[低脂（LF）; 10% kcal脂肪]或高脂饮食组（HF; 45% kcal脂肪）。饮食处理8周后，在整个灌注的肠系膜床（MB）和清除PVAT的离体肠系膜动脉中分析血管功能。乙酰胆碱（10（-9）-10（-4）M）和硝普钠（10（-12）-10（-5）M）的舒张反应在HF动物的整个MB中显著改善。HF组和LF组之间无PVAT的肠系膜动脉无明显差异。在HF小鼠中检测到的舒张反应的增强并不归因于从内皮细胞释放的一氧化氮（NO）的增加，也不归因于肌肉鸟苷酸环化酶的敏感性和/或活性的增加。4，5-二氨基荧光素二乙酸酯（DAF 2-DA）染色显示HF动物肠系膜PVAT显示NO生物利用度增加，其与血浆瘦素水平呈正相关。ob/ob小鼠的PVAT中没有γ-2DA染色，但在4周的瘦素替代后在这些动物中检测到。在这项研究中的主要发现是，适应性NO过量生产发生在PVAT在早期DIO，这可能是为了保护血管功能。（内分泌学151：3299-3306，2010）
Perivascular adipose tissue (PVAT) plays a paracrine role in regulating vascular tone. We hypothesize that PVAT undergoes adaptative mechanisms during initial steps of diet-induced obesity (DIO) which contribute to preserve vascular function. Four-week-old male C57BL/6J mice were assigned either to a control [low-fat (LF); 10% kcal from fat] or to a high-fat diet (HF; 45% kcal from fat). After 8 wk of dietary treatment vascular function was analyzed in the whole perfused mesenteric bed (MB) and in isolated mesenteric arteries cleaned of PVAT. Relaxant responses to acetylcholine (10(-9)-10(-4) M) and sodium nitroprusside (10(-12)-10(-5) M) were significantly ameliorated in the whole MB from HF animals. However, there was no difference between HF and LF groups in isolated mesenteric arteries devoid of PVAT. The enhancement of relaxant responses detected in HF mice was not attributable to an increased release of nitric oxide (NO) from the endothelium nor to an increased sensitivity and/or activity of muscular guanilylcyclase. Mesenteric PVAT of HF animals showed an increased bioavailability of NO, detected by 4,5-diaminofluorescein diacetate (DAF2-DA) staining, which positively correlated with plasma leptin levels. DAF-2DA staining was absent in PVAT from ob/ob mice but was detected in these animals after 4-wk leptin replacement. The main finding in this study is that adaptative NO overproduction occurs in PVAT during early DIO which might be aimed at preserving vascular function. (Endocrinology 151: 3299-3306, 2010)