Increase In Adipose Tissue Blood Flow Research Articles

Glucose-dependent insulinotropic polypeptide has impaired effect on abdominal, subcutaneous adipose tissue metabolism in obese subjects

Glucose-dependent insulinotropic polypeptide (GIP) appears to have a role in lipid metabolism. Recently, we showed that GIP in combination with hyperinsulinemia and hyperglycemia increases triglyceride uptake in abdominal, subcutaneous adipose tissue in lean humans. It has been suggested that increased GIP secretion in obesity will promote lipid deposition in adipose tissue. In light of the current attempts to employ GIP antagonists in the treatment and prevention of human obesity, the present experiments were performed in order to elucidate whether the adipose tissue lipid metabolism would be enhanced or blunted during a GIP, hyperinsulinemic and hyperglycemic (HI-HG) clamp in obese subjects with either normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). Sixteen obese (BMI>30 kg m(-2)) subjects were divided into two groups, based on their plasma glucose response to an oral glucose challenge: (i) NGT and (ii) IGT. Abdominal, subcutaneous adipose tissue lipid metabolism was studied by conducting measurements of arteriovenous concentrations of metabolites and regional adipose tissue blood flow (ATBF) during GIP (1.5 pmol kg(-1) min(-1)) in combination with a HI-HG clamp. In both groups, ATBF responses were significantly lower than what we have found previously in healthy, lean subjects (P<0.0001). The flow response was significantly lower in the IGT group than in the NGT group (P=0.03). It was not possible to show any increase in the lipid deposition in adipose tissue under the applied experimental conditions and likewise the circulating triglyceride (TAG) concentrations remained constant. The applied GIP, HI-HG clamp did not induce any changes in TAG uptake in adipose tissue in obese subjects. This may be due to a blunted increase in ATBF. These experiments therefore suggest that GIP does not have a major role in postprandial lipid metabolism in obese subjects.

Restoring ATBF: Dreaming the impossible dream?

Dear Sir: Knowledge of the longterm effect of weight loss on adipose tissue blood flow (ATBF) is scarce. We read with great interest the paper by Rossi et al. [3], reporting the results of a study using laser-Doppler flowmetry (LDF), where baseline thigh ATBF was lower in morbidly obese subjects compared to ageand sex-matched controls (4.8 vs. 79.9 perfusion units /PU). These results confirm several previous studies [4]. After one-year follow-up subsequent to Roux-en Y gastric bypass (RYGB) in obese patients, they observed a meaningful weight loss (−40 kg, e.g.−28%). This weight loss was associated with a slight but nevertheless significant increase in ATBF (up to 10.0 PU) although patients remained obese. The main limitations of the Rossi et al. study are linked to the inherent drawbacks of the LDF method, relating mainly to calibration, multiple Doppler shifts, tissue optical properties, motion artefacts, biological zero and impossibility to express the results in absolute values [2]. The gold-standard for ATBF measurement is the 133 xenon wash-out method, which should be combined with LDF in order to validate data obtained therewith [1]. Anemia, a frequent complication of RYGB, and antihypertensive drugs, which may influence adipose tissue perfusion [4], could also interfere with LDF measurements. However, no indication relating to these specific issues was provided in the paper. Additionally, the chosen site of measurement stands out as another scientific issue, because subcutaneous adipose tissue in the thigh is known to be much less active than in abdomen [4]. Rossi et al.’s conclusion to the effect that the slight increase in ATBF, observed one year after RYGB, is rather negligible, is sustained by another study [5] reporting on ATBF following a very low-calorie diet

Subcutaneous adipose tissue blood flow and vasomotion in morbidly obese patients: Long term effect of gastric bypass surgery

Since recent findings suggest a relationship between reduction in adipose tissue blood flow (ATBF) and metabolic or vascular complications in obese patients (Ob-pts), increase in ATBF may be considered as a further goal in the treatment of obesity, besides fat mass reduction. Therefore, this preliminary study aimed at assess subcutaneous ATBF and vasomotion in morbidly obese patients and whether sustained weight loss induced by Roux-en-Y gastric bypass (RYGB) affects the same parameters. Using laser-Doppler flowmetry (LDF) and spectral Fourier analysis, subcutaneous ATBF was measured and subcutaneous ATBF oscillations (ATBF-O) were analyzed - within three frequency intervals related to vasomotion - in 16 Ob-pts, before and about one year after RYGB, and in 10 lean, healthy control subjects (CS). Before RYGB, Ob-Pts showed an important reduction in subcutaneous ATBF compared to CS (4.8 ± 2.7 PU vs 79.9 ± 34.5 PU, respectively; p < 0.0001), as well as higher normalized power spectral density (N-PSD) values of subcutaneous ATBF-O, - related to vasomotion. One year after RYGB, sustained weight loss in Ob-pts was associated with a slight but significant increase in subcutaneous ATBF (10.0 ± 6.6 PU, p < 0.05) and with almost complete normalization in N-PSD values of ATBF-O, related to vasomotion, compared to before RYGB. The slight subcutaneous ATBF increase, we observed in Ob-pts after sustained weight loss, moves toward a desirable goal. This finding suggests verifying whether an even more sustained weight loss in Ob-pts could determine a greater increase in subcutaneous ATBF and/or, more importantly, it could also determine a significant increase in visceral ATBF.

Effect of Steel and Teflon Infusion Catheters on Subcutaneous Adipose Tissue Blood Flow and Infusion Counter Pressure in Humans

Subcutaneous tissue is an important target for drug deposition or infusion. A local trauma may induce alterations in local microcirculation and diffusion barriers with consequences for drug bioavailability. We examined the influence of infusion catheters' wear time on local microcirculation and infusion counter pressure. One steel catheter and one Teflon (Dupont, Wilmington, DE) catheter were inserted in subcutaneous, abdominal adipose tissue (SCAAT) in 10 healthy, lean men. The catheters were infused with isotonic saline at a rate of 10 microL/h for 48 h. Another steel catheter and a Teflon catheter were inserted contralateral to the previous catheters after 48 h. The infusion counter pressure was measured during a basal infusion rate followed by a bolus infusion. The measurements during a basal rate infusion were repeated after the bolus infusion. Adipose tissue blood flow (ATBF) was measured in SCAAT continuously. A significant increase in ATBF was observed with wear time for Teflon but not for steel catheters. Mean infusion pressure during the bolus phase increased significantly from 0 to 48 h for Teflon but not for steel catheters. ATBF and infusion counter pressure was similar between Teflon and steel catheters after acute catheter implantation and after wear time of 48 h. The maximum value of pressure during the bolus phase increased with wear time of a catheter. ATBF and bolus mean infusion pressure increased significantly with a wear time of 48 h in Teflon but not in steel catheters. The maximal pressure required to deliver a bolus infusion increased with wear time of a catheter. A higher maximal pressure was required to deliver a bolus infusion through a Teflon than through a steel catheter. We propose that the difference in infusion counter pressure and ATBF between Teflon and steel catheters with wear time may be explained by better biocompatibility of steel than Teflon.

Angiotensin II: a major regulator of subcutaneous adipose tissue blood flow in humans

We investigated the functional roles of circulating and locally produced angiotensin II (Ang II) in fasting and postprandial adipose tissue blood flow (ATBF) regulation and examined the interaction between Ang II and nitric oxide (NO) in ATBF regulation. Local effects of the pharmacological agents (or contralateral saline) on ATBF, measured with 133Xe wash-out, were assessed using the recently developed microinfusion technique. Fasting and postprandial (75 g glucose challenge) ATBF regulation was investigated in nine lean healthy subjects (age, 29 +/- 3 years; BMI, 23.4 +/- 0.7 kg m(-2)) using local Ang II stimulation, Ang II type 1 (AT1) receptor blockade, and angiotensin-converting enzyme (ACE) inhibition. Furthermore, NO synthase (NOS) blockade alone and in combination with AT1 receptor blockade was used to examine the interaction between Ang II and NO. Ang II induced a dose-dependent decrease in ATBF (10(-9)m: -16%, P = 0.04; 10(-7)m: -33%, P < 0.01; 10(-5)m: -53%P < 0.01). Fasting ATBF was not affected by ACE inhibition, but was increased by approximately 55% (P < 0.01) by AT(1) receptor blockade. NOS blockade induced a approximately 30% (P = 0.001) decrease in fasting ATBF. Combined AT1 receptor and NOS blockade increased ATBF by approximately 40% (P = 0.003). ACE inhibition and AT1 receptor blockade did not affect the postprandial increase in ATBF. We therefore conclude that circulating Ang II is a major regulator of fasting ATBF, and a major proportion of the Ang II-induced decrease in ATBF is NO independent. Locally produced Ang II does not appear to regulate ATBF. Ang II appears to have no major effect on the postprandial enhancement of ATBF.

Technical note: adipose tissue blood flow in miniature swine (Sus scrofa) using the 133xenon washout technique.

The purpose of this study was to examine the 133xenon washout technique as a viable method for measuring adipose tissue blood flow (ATBF) in swine. Using a total of 32 female Yucatan miniature swine (Sus scrofa), the partition coefficient for 133xenon in swine subcutaneous adipose tissue was determined and ATBF was measured at rest and under various physiological conditions. These conditions included feeding, anesthesia, epinephrine infusion, and acute exercise. The effects of epinephrine and acute exercise were examined in both sedentary and exercise-trained swine. The partition coefficient value for 133xenon in swine subcutaneous adipose tissue was 9.23+/-0.26 mL/g (mean +/- SD, n = 10). The average value for resting ATBF in swine was 3.98+/-2.72 mL/(100 g tissue-min) (n = 19). Feeding increased ATBF by approximately fivefold over fasting values, and isoflurane anesthesia significantly decreased ATBF compared to rest (1.64+/-1.12 vs 3.92+/-4.22 mL/[100 g x min], n = 10). A 30-min epinephrine infusion (1 microg/[kg BW x min]) significantly increased ATBF from a resting value of 3.13+/-2.61 to 10.35+/-5.31 mL/(100 g x min) (n = 12). Epinephrine infusion into exercise-trained swine increased ATBF to the same extent as when infused into sedentary swine. An acute, 20-min bout of exercise significantly increased ATBF in swine, and the sedentary swine showed a larger increase in ATBF than their exercise-trained littermates relative to rest: 7.83 vs 2.98 mL/(100 g x min). In conclusion, the 133xenon washout technique appears to be a viable method for measuring ATBF in swine; our findings are comparable to swine ATBF values reported using the microsphere method and are consistent with values reported in animal and human studies.

Effects of insulin on adipose tissue blood flow in man.

Adipose tissue blood flow (ATBF) rises after nutrient ingestion. It is not clear whether this is due to insulin. The aim of this study was to investigate the role of insulin in the regulation of subcutaneous ATBF. We have investigated the role of insulin in the regulation of ATBF in normal, healthy subjects in a three-step procedure to determine the functional level at which insulin may potentially exert its effect. Fifteen subjects were studied on two occasions. On the first visit, 75 g oral glucose was given. In the second, similar plasma concentrations of insulin and glucose were achieved by dynamic intravenous infusions of insulin and glucose. The increase in ATBF after oral glucose (4.2 +/- 1.4 ml min(-1) (100 g tissue)(-1), P = 0.01) was significantly greater (P < 0.05) than that after intravenous infusions (1.5 +/- 0.6 ml min(-1) (100 g tissue)(-1) P < 0.05). For the local delivery of potentially vasoactive substances and simultaneous measurement of ATBF, we describe a novel combination of methods, which we have called 'microinfusion'. We have used this technique to show that locally infused insulin, even at pharmacological concentrations, had no demonstrable effect on ATBF in nine subjects. We conclude that whilst insulin does not have a direct effect on ATBF, it is likely to be an important mediator, possibly acting via sympathetic activation. In the postprandial state, other candidate peptides and hormones are also likely to play important roles.

Relationship between blood pressure, metabolic variables and blood flow in obese subjects with or without non-insulin-dependent diabetes mellitus.

To assess the relationship between systemic blood pressure, metabolic variables and adipose tissue blood flow, we studied 55 subjects before and 36 subjects after an oral glucose load (100 g). The subjects were divided into four different groups: (a) young lean control subjects [age 31 +/- 1 years, mean +/- SE, BMI (body mass index) 22.7 +/- 0.4 kg m-2]; (b) young obese subjects (age 29 +/- 2 years, BMI 37.8 +/- 1.8 kg m-2); (c) middle-aged obese subjects (age 50 +/- 2 years, BMI 30.2 +/- 0.9 kg m-2); and (d) middle-aged obese non-insulin-dependent diabetic (NIDDM) subjects (age 54 +/- 2 years, BMI 30.0 +/- 0.7 kg m-2). Groups 2-4 demonstrated a low fasting adipose tissue blood flow (ATBF) and the increase in ATBF after oral glucose was impaired. A further impairment was present in NIDDM subjects. Systolic and diastolic blood pressure were also increased in groups 2-4 and further so in group 4. Fasting glucose, lactate and free fatty acid (FFA) levels correlated positively with the systolic blood pressure, whereas ATBF correlated negatively with the diastolic blood pressure. Furthermore, in the NIDDM subjects fasting lactate correlated closely with both the systolic (r = 0.649, P = 0.01) and diastolic (r = 0.626, P = 0.013) blood pressure. These data suggest a close relationship between insulin resistance and regulation of adipose tissue blood flow as well as blood pressure.

Regulation of fatty acid delivery in vivo.

Adipose tissue triacylglycerol (TG) constitutes by far the largest energy store in the body. In order for this TG to be used as a substrate for oxidative metabolism, it has to be exported from adipose tissue and transported to the tissues where it will be used. Following hydrolysis of stored TG, non-esterified fatty acids (NEFA) leave the adipocyte and enter the plasma. Unlike tissues such as skeletal muscle which extract plasma NEFA, in adipose tissue the flow of fatty acids across the cell membrane is bi-directional, outward in times of net fat mobilization such as fasting and exercise, and inward during the postprandial period. Factors regulating NEFA delivery in vivo include hormonal and nervous stimulation of lipolysis, and a variety of factors, local and systemic, which oppose this by suppressing lipolysis. Adipose tissue blood flow (ATBF) is also important. ATBF is increased in states of fat mobilization and fat deposition, although there is evidence that during strenuous exercise the increase in ATBF is not sufficient for export of all the NEFA made available from lipolysis. There are well-documented regional variations in lipolysis. The intra-abdominal depots appear to have the highest rates of TG turnover, the subcutaneous abdominal an intermediate rate, and the gluteal-femoral depots to have relatively sluggish turnover. However, much of the evidence for this derives from studies of isolated adipocytes, and confirmation in vivo is much needed. There are links between abdominal fat deposition and risk of cardiovascular disease which may be mediated through increased fatty acid delivery from abdominal fat depots. The ability of exercise specifically to decrease intra-abdominal fat stores may be yet another health benefit of regular exercise.

Human adipose tissue blood flow during prolonged exercise, III. Effect of F-adrenergic blockade, nicotinic acid and glucose infusion

Subcutaneous adipose tissue blood flow (ATBF) was measured in six male subjects by the 133Xe-washout technique during 3-4 h of exercise at a work load corresponding to an oxygen uptake of about 1.71/min. The measurements were done during control conditions, during blockade of lipolysis by nicotinic acid, during acute i.v. beta-adrenergic blockade by propranolol, and during continuous i.v. infusion of glucose. The most pronounced lipid mobilization and utilization during work was seen in the control experiments where ATBF rose 3-fold on average from the initial rest period to the third hour of work. No increase in lipolysis and no increase in ATBF were found when lipolysis was blocked by nicotinic acid (0.3 g/h). Propranolol treatment (0.15 mg/kg) reduced lipolysis and nearly abolished the increase in ATBF during exercise. Intravenous administration of glucose (about 0.25 g/min) did not influence lipid metabolism (evaluated by the respiratory quotient) nor did it reduce the ATBF response to exercise. These results are inconsistent with the hypothesis that increase in ATBF during exercise is elicited via direct stimulation of vascular beta1-receptors, while they are not in disagreement with the hypothesis that adipose tissue vasodilation during exercise is secondary to metabolic events connected to lipolysis.