Nitric Oxide and β-Adrenergic Stimulation Are Major Regulators of Preprandial and Postprandial Subcutaneous Adipose Tissue Blood Flow in Humans

Abstract

Background-Blood flow mediates the metabolic and endocrine roles of adipose tissue. We have previously shown that the postprandial adipose tissue blood flow (ATBF) increase is dependent on insulin sensitivity. However, subcutaneous local insulin delivery had no demonstrable effect on either preprandial or postprandial ATBF. We hypothesized that insulin may act indirectly via sympathetic activation, mainly in the postprandial period, and that nitric oxide may be an overall major regulator of subcutaneous ATBF. Methods and Results-We investigated the endogenous preprandial and postprandial regulation of ATBF by applying local tissue blockade of ␤-adrenergic (propranolol), ␣-adrenergic (phentolamine and yohimbine), and nitric oxide (N G -monomethyl-L-arginine, L-NMMA) regulation of blood flow. Healthy subjects (body mass index, 18 to 31 kg/m 2 ) were challenged with 75 g glucose for endogenous stimulation of ATBF. We used the novel "microinfusion" technique, which allows for simultaneous local delivery of pharmacological agents (or contralateral saline) and measurement of ATBF with the 133 Xe washout method. Compared with control, the preprandial ATBF was not affected by propranolol but was increased by 21% (PϽ0.013) and 15% (Pϭ0.004) with phentolamine and yohimbine, respectively. A decrease of 42% (2.97Ϯ0.33 versus 4.75Ϯ0.47 mL · min Ϫ1 · 100 g tissue

The mechanism of flow-induced dilation in human adipose arterioles involves hydrogen peroxide during CAD

“…However, this is the first study to our knowledge demonstrating NO-mediated FID in the isolated human adipose microcirculation. This observation is mechanistically consistent with studies linking the postprandial increase in adipose tissue blood flow in humans to NO (2).…”

“…This important endothelial mechanism of vasodilation occurs in virtually every vascular bed and, in large arteries, may be critical for preventing atherosclerosis through release of the endothelium-derived antiproliferative compounds nitric oxide (NO) and prostacyclin (PGI 2 ) (21,25,39,51). Many of the studies implicating the role of NO (24) and PGI 2 (26) in FID have been performed in animal models in the absence of coronary artery disease (CAD). However, no studies have evaluated the mechanism of FID in isolated human microvessels from human visceral adipose with or without CAD.…”

Gluteofemoral body fat as a determinant of metabolic health

“…50,51 Interestingly, the postprandial rise in ATBF is not a direct insulin effect but is mainly mediated through catecholamines and nitric oxide. 52,53 ATBF changes of the abdominal fat depot have been well studied in different settings; however, little is known regarding ATBF regulation in the lower-body fat depot. Gluteal fat was shown to have lower basal ATBF, 44 and in lean women, femoral ATBF showed an attenuated increase during systemic adrenaline stimulation compared with abdominal fat.…”

Subcutaneous adipose tissue blood flow varies between superior and inferior levels of the anterior abdominal wall

“…The cannulae were perfused for 1 min at 60 ml min À1 with saline to wash the 133 xenon through the dead volume, and for a further 40-60 min at 2 ml min À1 to allow for equilibration (ie to allow for the disappearance of the hyperaemia and the diffusion/equilibration of the xenon into the tissue). After 20 min baseline recording, an extended baseline period of 60 min was recorded in half of the probes (the other probes were used for drug infusion studies, which are reported elsewhere 28 ). At time þ 60 min the subject was given the 75 g oral glucose in 200 ml of lemon-flavoured water, while infusions continued for a further 120 min.…”