Abdominal Adipose Tissue Blood Flow Research Articles

GIP-induced vasodilation in human adipose tissue involves capillary recruitment.

Glucose-dependent insulinotropic polypeptide (GIP) in combination with hyperinsulinemia increase blood flow and triglyceride clearance in subcutaneous abdominal adipose tissue in lean humans. The present experiments were performed to determine whether the increase involves capillary recruitment. Eight lean healthy volunteers were studied before and after 1 h infusion of GIP or saline during a hyperglycemic–hyperinsulinemic clamp, raising plasma glucose and insulin to postprandial levels. Subcutaneous abdominal adipose tissue blood flow (ATBF) was measured by the 133Xenon clearance technique, and microvascular blood volume was determined by contrast-enhanced ultrasound imaging. During infusion of saline and the clamp, both ATBF (2.7 ± 0.5 mL/min 100 g/tissue) and microvascular blood volume remained unchanged throughout the experiments. During GIP infusion and the clamp, ATBF increased ~fourfold to 11.4 ± 1.9 mL/min 100 g/tissue, P < 0.001. Likewise, the contrast-enhanced ultrasound signal intensity, a measure of the microvascular blood volume, increased significantly 1 h after infusion of GIP and the clamp (P = 0.003), but not in the control experiments. In conclusion, the increase in ATBF during GIP infusion involves recruitment of capillaries in healthy lean subjects, which probably increases the interaction of circulating lipoproteins with lipoprotein lipase, thus promoting adipose tissue lipid uptake.

The Gluco- and Liporegulatory and Vasodilatory Effects of Glucose-Dependent Insulinotropic Polypeptide (GIP) Are Abolished by an Antagonist of the Human GIP Receptor.

A truncated form of human glucose-dependent insulinotropic polypeptide (GIP), GIP(3-30)NH2, was recently identified as an antagonist of the human GIP receptor. This study examined the ability of GIP(3-30)NH2 to antagonize the physiological actions of GIP in glucose metabolism, subcutaneous abdominal adipose tissue blood flow (ATBF), and lipid metabolism in humans. Eight lean subjects were studied by measuring arteriovenous concentrations of metabolites and ATBF on three different occasions during hyperglycemic-hyperinsulinemic clamps with concomitant infusions of GIP, GIP(3-30)NH2, or both GIP and GIP(3-30)NH2 During infusion of GIP(3-30)NH2 alone and in combination with GIP, insulin levels and the total glucose amount infused to maintain the clamp were lower than during GIP alone. In addition, ATBF remained constant during the antagonist and increased only slightly in combination with GIP, whereas it increased fivefold during GIP alone. Adipose tissue triacylglyceride (TAG) and glucose uptake decreased, and the free fatty acid/glycerol ratio increased during the antagonist alone and in combination with GIP. The changes in glucose infusion rates and plasma insulin levels demonstrate an inhibitory effect of the antagonist on the incretin effect of GIP. In addition, the antagonist inhibited GIP-induced increase in ATBF and decreased the adipose tissue TAG uptake, indicating that GIP also plays a crucial role in lipid metabolism.

Acute Hypercortisolemia Exerts Depot-Specific Effects on Abdominal and Femoral Adipose Tissue Function.

Context:Glucocorticoids have pleiotropic metabolic functions, and acute glucocorticoid excess affects fatty acid metabolism, increasing systemic lipolysis. Whether glucocorticoids exert adipose tissue depot-specific effects remains unclear.Objective:To provide an in vivo assessment of femoral and abdominal adipose tissue responses to acute glucocorticoid administration.Design and Outcome Measures:Nine healthy male volunteers were studied on two occasions, after a hydrocortisone infusion (0.2 mg/kg/min for 14 hours) and a saline infusion, respectively, given in randomized double-blind order. The subjects were studied in the fasting state and after a 75-g glucose drink with an in vivo assessment of femoral adipose tissue blood flow (ATBF) using radioactive xenon washout and of lipolysis and glucose uptake using the arteriovenous difference technique. In a separate study (same infusion design), eight additional healthy male subjects underwent assessment of fasting abdominal ATBF and lipolysis only. Lipolysis was assessed as the net release of nonesterified fatty acids (NEFAs) from femoral and abdominal subcutaneous adipose tissue.Results:Acute hypercortisolemia significantly increased basal and postprandial ATBF in femoral adipose tissue, but the femoral net NEFA release did not change. In abdominal adipose tissue, hypercortisolemia induced substantial increases in basal ATBF and NEFA release.Conclusions:Acute hypercortisolemia induces differential lipolysis and ATBF responses in abdominal and femoral adipose tissue, suggesting depot-specific glucocorticoid effects. Abdominal, but not femoral, adipose tissue contributes to the hypercortisolemia-induced systemic NEFA increase, with likely contributions from other adipose tissue sources and intravascular triglyceride hydrolysis.

Glucagon‐like peptide‐1 elicits vasodilation in adipose tissue and skeletal muscle in healthy men

In healthy subjects, we recently demonstrated that during acute administration of GLP‐1, cardiac output increased significantly, whereas renal blood flow remained constant. We therefore hypothesize that GLP‐1 induces vasodilation in other organs, for example, adipose tissue, skeletal muscle, and/or splanchnic tissues. Nine healthy men were examined twice in random order during a 2‐hour infusion of either GLP‐1 (1.5 pmol kg−1 min−1) or saline. Cardiac output was continuously estimated noninvasively concomitantly with measurement of intra‐arterial blood pressure. Subcutaneous, abdominal adipose tissue blood flow (ATBF) was measured by the 133Xenon clearance technique. Leg and splanchnic blood flow were measured by Fick's Principle, using indocyanine green as indicator. In the GLP‐1 study, cardiac output increased significantly together with a significant increase in arterial pulse pressure and heart rate compared with the saline study. Subcutaneous, abdominal ATBF and leg blood flow increased significantly during the GLP‐1 infusion compared with saline, whereas splanchnic blood flow response did not differ between the studies. We conclude that in healthy subjects, GLP‐1 increases cardiac output acutely due to a GLP‐1‐induced vasodilation in adipose tissue and skeletal muscle together with an increase in cardiac work.

Insulin Plays a Permissive Role for the Vasoactive Effect of GIP Regulating Adipose Tissue Metabolism in Humans.

Glucose-dependent insulinotropic polypeptide (GIP) in combination with hyperinsulinemia increases blood flow and triglyceride (TAG) clearance in subcutaneous (sc) abdominal adipose tissue in lean humans. The present experiments were performed to further investigate the role of insulin for the vasoactive effect of GIP in adipose tissue metabolism and whether the vasodilatory effect of GIP is dependent on C-peptide. Six lean healthy subjects were studied. The sc abdominal adipose tissue metabolism was assessed by Fick's principle during GIP infusion (1.5 pmol/kg/min) in combination with 1) euglycemic-high insulinemic clamp (Eugluc-Hiinsu), raising plasma insulin concentrations to postprandial levels, 2) hyperglycemic-euinsulinemic clamp (Hygluc-Euinsu), and 3) hyperglycemic-hyperinsulinemic clamp, raising plasma insulin concentrations to supraphysiological levels. During the hyperglycemic clamps, endogenous insulin and C-peptide secretion were inhibited by infusion of the somatostatin analogue octreotide. During GIP infusion, Eugluc-Hiinsu, and hyperglycemic-hyperinsulinemic clamps, sc abdominal adipose tissue blood flow (ATBF) was similar and increased from 2.1 ± 0.2 and 2.2 ± 0.4 ml min(-1) (100 g tissue)(-1) to 7.1 ± 0.6 and 7.6 ± 0.1 ml min(-1) (100 g tissue)(-1), respectively (P < .01). ATBF remained virtually constant (2.7 ± 0.4 ml min(-1) [100 g tissue](-1)) during Hygluc-Euinsu and GIP infusion. In addition, adipose tissue TAG clearance increased significantly (P = .03), whereas free fatty acid output (P = .01), glycerol output (P = .02) and free fatty acid/glycerol release ratio (P = .04) decreased during the Eugluc-Hiinsu clamp compared to Hygluc-Euinsu clamp with GIP. In healthy lean humans, insulin is permissive for GIP to induce an increase in blood flow and TAG clearance in sc abdominal adipose tissue. This effect is independent of C-peptide.

The dynamics of the microcirculation in the subcutaneous adipose tissue is impaired in the postprandial state in type 2 diabetes

Postprandially, the blood flow and uptake of non-esterified fatty acids increase concomitantly in the abdominal subcutaneous adipose tissue in healthy subjects. In insulin-resistant subjects, this postprandial blood flow increase is blunted. We have previously found that the postprandial adipose tissue blood flow (ATBF) increase is accompanied by capillary recruitment in healthy subjects. The aim of the present study was to investigate whether the postprandial capillary recruitment in adipose tissue is affected in type 2 diabetes mellitus. Eight type 2 diabetic overweight male subjects and eight age- and weight-matched healthy subjects were studied. Contrast-enhanced ultrasound imaging was applied to study the microvascular volume in abdominal subcutaneous adipose tissue and in forearm skeletal muscle in the fasting state and 60, 120 and 180 min after a 75-g oral glucose load. Abdominal subcutaneous ATBF was measured using (133) Xenon washout technique, and forearm skeletal muscle blood flow was assessed by venous occlusion plethysmography. In the healthy, overweight subjects, ATBF increased and concomitantly capillary recruitment took place after glucose ingestion. No significant changes were found in the ATBF or in capillary recruitment in the type 2 diabetic subjects. There was no significant blood flow or microvascular blood volume changes in forearm skeletal muscle in either of the groups. After an oral glucose load, the abdominal ATBF and microvascular blood volume changes in abdominal subcutaneous adipose tissue are impaired in overweight type 2 diabetic subjects compared to weight-matched healthy subjects.

Regulation of subcutaneous adipose tissue blood flow is related to measures of vascular and autonomic function

Appropriate blood vessel function is important to cardiovascular health. Adipose tissue plays an important role in metabolic homoeostasis, and subcutaneous abdominal ATBF (adipose tissue blood flow) is responsive to nutritional stimuli. This response is impaired in obesity, suggesting parallels with endothelial function. In the present study, we assessed whether regulation of ATBF is related to the regulation of endothelial function, assessed by FMD (flow-mediated vasodilatation) of the brachial artery. Impaired FMD is a marker of atherosclerotic risk, so we also assessed relationships between ATBF and a marker of atherosclerosis, common carotid artery IMT (intima-media thickness). As ATBF is responsive to sympatho-adrenal stimuli, we also investigated relationships with HRV (heart rate variability). A total of 79 healthy volunteers (44 female) were studied after fasting and after ingestion of 75 g of glucose. FMD, fasting ATBF and the responsiveness of ATBF to glucose were all negatively related to BMI (body mass index), confirming the adverse cardiovascular effects of adiposity. FMD was related to fasting ATBF (rs=0.32, P=0.008) and, at least in males, this relationship was independent of BMI (P=0.02). Common carotid artery IMT, measured in a subset of participants, was negatively related to fasting ATBF [rs=-0.51, P=0.02 (n=20)]. On the other hand, ATBF responsiveness to glucose had no relationship with either FMD or IMT. In multiple regression models, both fasting and stimulated ATBF had relationships with HRV. In conclusion, our results show that the regulation of ATBF has features in common with endothelial function, but also relationships with autonomic cardiovascular control as reflected in HRV.

Microdialysis assessment of local adipose tissue lipolysis during beta-adrenergic stimulation in upper-body-obese subjects with type II diabetes.

The present study was designed to investigate indicators of abdominal adipose tissue lipolysis (microdialysis), and subcutaneous adipose tissue blood flow and whole-body lipolysis, in obesity-associated type II diabetes during overnight-fasted conditions (baseline) and during intravenous infusion of the non-selective beta-agonist isoprenaline. Basal subcutaneous adipose tissue blood flow and isoprenaline-induced increases in adipose tissue blood flow were not significantly different between subjects with type II diabetes and non-obese, non-diabetic controls. Adipose tissue interstitial glycerol concentrations were significantly higher in subjects with type II diabetes compared with controls (P<0. 01), and during isoprenaline infusion there was a decrease in interstitial glycerol in both groups (P<0.001). Arterial glycerol concentrations were higher in subjects with type II diabetes compared with controls (P<0.05), whereas the increases in arterial glycerol concentration in response to isoprenaline infusion were of a similar magnitude in the two groups. Estimated subcutaneous adipose tissue glycerol release was not significantly different between the groups (controls and subjects with type II diabetes: baseline, -129+/-32 and -97+/-72 micromol.min(-1).100 g(-1) adipose tissue respectively; isoprenaline, -231+/-76 and -286+/-98 micromol. min(-1).100 g(-1) respectively). Values for fat oxidation were not significantly different between groups, whereas the isoprenaline-induced increase in fat oxidation tended to be less pronounced in subjects with type II diabetes compared with controls (0.022+/-0.008 and 0.038+/-0.003 g/min respectively; P=0.058). Thus estimated basal subcutaneous adipose tissue glycerol release, expressed per unit of fat mass, is not different in controls and in subjects with type II diabetes. Additionally, the isoprenaline-induced increases in indicators of local abdominal subcutaneous adipose tissue, systemic lipolysis and abdominal adipose tissue blood flow responses were comparable in obese subjects with type II diabetes and in controls. The last two findings contrast with previous data from obese subjects, indicating that the regulation of lipolysis may differ in obesity and obesity-associated type II diabetes.

Subcutaneous abdominal adipose tissue blood flow: variation within and between subjects and relationship to obesity.

1. We assessed the variation in subcutaneous abdominal adipose tissue blood flow within and between subjects and investigated whether it is correlated with body mass index. 2. We measured body mass index and subcutaneous abdominal adipose tissue blood flow in 38 fasting subjects on the same day and on different days and, in a subgroup of 16 subjects, after a mixed meal. 3. In 190 measurements in the fasted state, subcutaneous abdominal adipose tissue blood flow was significantly more variable between subjects than could be accounted for by the within-subject variation alone. Subcutaneous abdominal adipose tissue blood flow was also significantly more variable between days within subjects than could be accounted for by within-day variation alone. Fasting and post-prandial subcutaneous abdominal adipose tissue blood flow were negatively correlated with body mass index, as was the post-prandial rise in subcutaneous abdominal adipose tissue blood flow. Multiple regression analysis showed that fasting blood flow was not dependent on insulin concentration after allowing for body mass index. There was no correlation between post-prandial subcutaneous abdominal adipose tissue blood flow and insulin concentration. 4. Insulin does not appear to have a direct vasodilatory effect in subcutaneous adipose tissue. Obese subjects have lower fasting and post-prandial subcutaneous abdominal adipose tissue blood flow. This may be because of a blunted response to sympathetic stimulation, or it may be another aspect of the insulin-resistant state.