Glucagon-Like Peptide-1 (7-36)-Amide and Exendin-4 Strongly Stimulate the Hypothalamic-Pituitary-Adrenal Axis in Rodents and in Healthy or Diabetic Humans

摘要

Perivascular adipose tissue (PVAT) plays a paracrine role in regulating vascular tone. We hypothesize that PVAT undergoes adaptative mechanisms during initial steps ofdiet-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% kcalfrom 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) andinisolatedmesentericarteriescleanedofPVAT.Relaxantresponsestoacetylcholine(10 ?9 –10 ?4 M)andsodiumniroprusside(10 ?12 –10 ?5 M)weresignificantlyamelioratedinthewholeMBfromHFanimals.However,therewasnodifferencebetweenHFandLFgroupsinisolatedmesentericarteriesdevoidofPVAT.Theenhancementofrelaxantresponses 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 ofmuscular 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 5-wk leptinreplacement. 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.