Application of in vivo microdialysis to measure leptin concentrations in adipose tissue

Microdialysis is a relatively new in vivo sampling technique, which allows repeated collecting of interstitial fluid and infusion of effector molecules into the tissue without influencing whole body function. The possibility of using microdialysis catheter with a large-pore size dialysis membrane (100 kDa) to measure concentrations of the adipocyte-derived peptide hormone leptin in interstitial fluid of adipose tissue was explored. Krebs–Henseleit buffer with 40 g/l dextran-70 was used to prevent perfusion fluid loss across the dialysis membrane. The relative recovery of leptin in vitro was determined using CMA/65 microdialysis catheter (100 kDa cut-off, membrane length 30 mm; CMA, Stockholm, Sweden) and four perfusion rates were tested (0.5, 1.0, 2.0, 5.0 μl/min). Furthermore, the microdialysis catheter CMA/65 was inserted into subcutaneous abdominal adipose tissue of 11 healthy human subjects and leptin concentrations in the interstitial fluid of adipose tissue in vivo were measured. The present findings are the first documentation on the use of microdialysis to study local leptin concentrations in the interstitial fluid of adipose tissue.     

Increased subcutaneous abdominal tissue norepinephrine levels in patients with anorexia nervosa: an in vivo microdialysis study

The present study was designed to measure interstitial levels of norepinephrine-regulating lipolysis (NE) in subcutaneous abdominal adipose tissue of anorexia nervosa (AN) patients and control subjects under basal conditions and after the local administration of an inhibitor of NE re-uptake, maprotiline. In vivo microdialysis technique was used to assess subcutaneous adipose NE levels in five women with AN (body mass index 14.62+/-0.47 kg/m(2)) and six age-matched controls (22.1+/-0.52 kg/m(2)). NE was assayed using high performance liquid chromatography with electrochemical detection after batch alumina extraction. Measured basal adipose tissue NE levels reflecting its interstitial levels were significantly increased in AN patients compared to the controls (106.0+/-20.9 vs. 40.0+/-5.0 pg/ml). The local maprotiline administration resulted in a significant increase in adipose tissue NE levels (AN patients: 440.0+/-28.6 vs. 202.0+/-33.0 pg/ml in the controls) in both groups. Markedly increased subcutaneous abdominal adipose tissue NE levels in AN patients compared to control subjects reflect increased sympathetic nervous system activity but not altered membrane noradrenergic transporter system in anorexia nervosa patients.     

Endurance training and GH administration in elderly women: effects on abdominal adipose tissue lipolysis

In the present study, the effect of endurance training alone and endurance training combined with recombinant human growth hormone (rhGH) administration on subcutaneous abdominal adipose tissue lipolysis was investigated. Sixteen healthy women [age 75 +/- 2 yr (mean +/- SE)] underwent a 12-wk endurance training program on a cycle ergometer. rhGH was administered in a randomized, double-blinded, placebo-controlled design in addition to the training program. Subcutaneous abdominal adipose tissue lipolysis was estimated by means of microdialysis combined with measurements of subcutaneous abdominal adipose tissue blood flow (ATBF; (133)Xe washout). Whole body fat oxidation was estimated simultaneously by indirect calorimetry. Before and after completion of the training program, measurements were performed both at rest and during 60 min of continuous cycling at a workload corresponding to 60% of pretraining peak oxygen uptake. Endurance training alone did not affect subcutaneous abdominal adipose tissue lipolysis either at rest or during exercise, as reflected by identical levels of interstitial adipose tissue glycerol, subcutaneous abdominal ATBF, and plasma nonesterified fatty acids before and after completion of the training program. Similarly, no effect on subcutaneous abdominal adipose tissue lipolysis was observed when combining endurance training with rhGH administration. However, in both the placebo and the GH groups, fat oxidation was significantly increased during exercise performed at the same absolute workload after completion of the training program. We conclude that the changed lipid metabolism during exercise observed after endurance training alone or after endurance training combined with rhGH administration is not due to alterations in subcutaneous abdominal adipose tissue metabolism in elderly women.     

Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men [insulin infusion rates: 10,000 (step I), 20,000 (step II), and 150,000 (step III) microU x min(-1) x m(-2)]. Glucose and glycerol concentrations were measured in arterial blood and also by microdialysis in interstitial fluid in periumbilical, subcutaneous adipose tissue and in quadriceps femoris muscle (glucose only). Adipose tissue blood flow was measured by (133)Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration difference was increased in T during the clamp but not in S subjects in both adipose tissue and muscle [adipose tissue: step I (n = 8), 0.48 +/- 0.18 mM (T), 0.23 +/- 0.11 mM (S); step II (n = 8), 0.19 +/- 0.09 (T), -0.09 +/- 0.24 (S); step III (n = 5), 0.47 +/- 0.24 (T), 0.06 +/- 0.28 (S); (T: P < 0.001, S: P > 0.05); muscle: step I (n = 4), 1. 40 +/- 0.46 (T), 0.31 +/- 0.21 (S); step II (n = 4), 1.14 +/- 0.54 (T), -0.08 +/- 0.14 (S); step III (n = 4), 1.23 +/- 0.34 (T), 0.24 +/- 0.09 (S); (T: P < 0.01, S: P > 0.05)]. Interstitial glycerol concentration decreased faster in T than in S subjects [half-time: T, 44 +/- 9 min (n = 7); S, 102 +/- 23 min (n = 5); P < 0.05]. In conclusion, training enhances insulin sensitivity of glucose uptake in subcutaneous adipose tissue and in skeletal muscle. Furthermore, interstitial glycerol data suggest that training also increases insulin sensitivity of lipolysis in subcutaneous adipose tissue. Insulin per se does not influence subcutaneous adipose tissue blood flow.     

Leptin concentrations in the abdominal subcutaneous adipose tissue of patients with anorexia nervosa assessed by in vivo microdialysis

OBJECTIVE: The adipocyte-derived hormone leptin is involved in energy metabolism and body weight regulation. Plasma leptin concentrations are significantly reduced in patients with anorexia nervosa (AN) and with severe malnutrition. Whether reduced plasma leptin is reflected by its decreased production by the adipose tissue is unknown. METHODS: In the present study we measured leptin concentrations locally in the abdominal subcutaneous adipose tissue of 9 female AN patients and 11 healthy controls by in vivo microdialysis. RESULTS: Adipose tissue free leptin levels were not different in patients with AN compared to controls (2.59+/-1.99 vs 2.36+/-0.25 ng/ml, P>0.05). Plasma leptin soluble receptor (sOb-R) levels were significantly higher in patients with AN than in healthy subjects (58.05+/-38.69 vs 12.79+/-5.08 U/ml, P<0.01). The area of adipocyte in AN was considerably smaller than in the controls (183+/-104.01 microm2 compared to 2145.8+/-1003.41). CONCLUSIONS: We conclude that decreased plasma leptin levels in patients with AN are not directly related to dialysate leptin levels in the abdominal subcutaneous adipose tissue.     

Combination of microdialysis and glucosensor permits continuous (on line) SC glucose monitoring in a patient operated device. II. Evaluation in animals.

The microdialysis technique was used for following the glucose content of the extracellular subcutaneous (SC) fluid under varying blood glucose levels in rats. The glucose content in the microdialysis perfusion fluid was continuously analyzed by means of the measuring flow chamber of an ex vivo glucose monitor. In six ChBB rats blood glucose levels were varied between 40 mg/dl and 575 mg/dl by intravenous (IV) infusion of glucose and by SC injections of insulin, respectively. After a running-in period of about half an hour, the glucose content in the perfusion fluid was closely related to the blood glucose concentration (r > 0.92) up to a time period of 6 hrs. The "relative recovery" rate of glucose by the microdialysis probe in the SC tissue varied within the 6 experimental sessions. The relative recovery rate could be shown to be not dependent on the absolute blood glucose levels in the individual rat within the glucose concentration range tested.     

Calibration in dogs of a subcutaneous miniaturized glucose sensor using a glucose meter for blood glucose determination.

The feasibility of calibrating a glucose sensor by using a wearable glucose meter for blood glucose determination and moderate variations of blood glucose concentration was assessed. Six miniaturized glucose sensors were implanted in the subcutaneous tissue of conscious dogs, and the parameters used for the in vivo calibration of the sensor (sensitivity coefficient and extrapolated current in the absence of glucose) were determined from values of blood glucose and sensor response obtained during glucose infusion. (1) Venous plasma glucose level and venous total blood glucose level were measured simultaneously on the same sample, using a Beckman analyser and a Glucometer II, respectively. The regression between plasma glucose (x) and whole blood glucose (y) was y = 1.12x-0.08 mM (n = 114 values, r = 0.96, p = 0.0001). The error grid analysis indicated that the use of a Glucometer II for blood glucose determination was appropriate in dogs. (2) The in vivo sensitivity coefficients were 0.57 +/- 0.11 nA mM-1 when determined from plasma glucose, and 0.51 +/- 0.07 nA mM-1 when determined from whole blood glucose (t = 1.53, p = 0.18, n.s.). The background currents were 0.88 +/- 0.57 nA when determined from plasma glucose, and 0.63 +/- 0.77 nA when determined from whole blood glucose (t = 0.82, p = 0.45, n.s.). (3) The regression equation of the estimation of the subcutaneous glucose level obtained from the two methods was y = 1.04x + 0.56 mM (n = 171 values, r = 0.98, p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Histamine pharmacokinetics in tumor and host tissues after bolus-dose administration in the rat

In this study, we estimated interstitial histamine concentrations in normal and malignant tissues after a single intravenous (i.v.) injection of 0.5 mg/kg histamine dihydrochloride in the rat. The microdialysis technique was used to collect interstitial fluid from subcutis, liver and a NGW adenocarcinoma. Histamine was absorbed with equal efficiency to all tissues (t 1/2 AB 3.9-7.7 minutes) but maximum concentration (Cmax; nmol/l) of histamine was higher in liver (2,388 +/- 357) than in subcutis (951 +/- 125) (p < 0.01) and subcutaneous tumor (523 +/- 140) (p = 0.01) and, moreover, Cmax in liver tumor (1,752 +/- 326) was higher than in subcutaneous tumor (p = 0.01). The tl/2 elimination was significantly longer in subcutis and subcutaneous tumor than in liver and liver tumor. Area under the curve (AUC; mmol-min/l) for histamine was significantly lower in subcutaneous tumor (9.8 +/- 2.3) than in liver (17.6 +/- 1.9) (p = 0.03) and liver tumor (15.8 +/- 1.8) (p = 0.03). Local tissue blood flow as assessed by the 14C-ethanol method was not significantly altered by the histamine administration. In conclusion, after an i.v. injection of histamine dihydrochloride a higher maximum concentration and AUC of histamine was reached in liver and liver tumor than in subcutaneous tissues.     

Lack of antilipolytic effect of lactate in subcutaneous abdominal adipose tissue during exercise.

The purpose of our study was to evaluate the potential inhibition of adipose tissue mobilization by lactate. Eight male subjects (age, 26. 25 +/- 1.75 yr) in good physical condition (maximal oxygen uptake, 59.87 +/- 2.77 ml. kg-1. min-1; %body fat, 10.15 +/- 0.89%) participated in this study. For each subject, two microdialysis probes were inserted into abdominal subcutaneous tissue. Lactate (16 mM) was perfused via one of the probes while physiological saline only was perfused via the other, both at a flow rate of 2.5 microl/min. In both probes, ethanol was also perfused for adipose tissue blood flow estimation. Dialysates were collected every 10 min during rest (30 min), exercise at 50% maximal oxygen consumption (120 min), and recovery (30 min) for the measurement of glycerol concentration. During exercise, glycerol increased significantly in both probes. However, no differences in glycerol level and ethanol extraction were observed between the lactate and control probes. These findings suggest that lactate does not impair subcutaneous abdominal adipose tissue mobilization during exercise.     

Drug distribution studies with microdialysis. III: Extracellular concentration of caffeine in adipose tissue in man

Microdialysis was applied to estimate the extracellular concentration of caffeine in subcutaneous abdominal adipose tissue of five healthy volunteers after oral administration of approximately 5 mg/kg (300 or 400 mg) of caffeine. The peak extracellular levels were in the range of 20 - 80 microM. The time-course in blood and in extracellular fluid was similar but the plateau concentrations were not closely correlated. The estimated mean concentration of five individuals was similar in blood and extracellular fluid. The intraindividual variation between probes was found to be small compared to the interindividual variation (8% versus 43%). It is concluded that microdialysis yield useful data on drug distribution in man and that distribution to adipose tissue may not strictly follow the concentrations in blood. A comparison with available information of the in vitro properties of caffeine shows that the levels attained in the extracellular fluid were too small to significantly affect phosphodiesterase but sufficiently high to block adenosine receptors.     

Measurement of interstitial albumin in human skeletal muscle and adipose tissue by open-flow microperfusion

The absolute concentration of albumin was measured in the interstitial fluid of subcutaneous adipose tissue and skeletal muscle in six healthy volunteers by combining the method of open-flow microperfusion and the no-net-flux calibration technique. By use of open-flow microperfusion, four macroscopically perforated double lumen catheters were inserted into the tissue regions of interest and constantly perfused. Across the macroscopic perforations of the catheters interstitial fluid was partially recovered in the perfusion fluid. Catheters were perfused with five solutions, each containing different concentrations of albumin. Absolute interstitial albumin concentrations were calculated by applying linear regression analysis to perfusate vs. sampled albumin concentration (no-net-flux calibration technique). Interstitial albumin concentrations were significantly lower (P < 0.0001) in adipose tissue (7.36 g/l; r = 0.99, P < 0.0003; range: 4.3-10.7 g/l) and in skeletal muscle (13.25 g/l; r = 0.99, P < 0.0012; range: 9.7 to 15.7 g/l) compared with the serum concentration (48.9 +/- 0.7 g/l, mean +/- SE, n = 6; range: 46.4-50.4 g/l). Furthermore, interstitial albumin concentrations were significantly higher in skeletal muscle compared with adipose tissue (P < 0.01). The study indicates that open-flow microperfusion allows stable sampling of macromolecules from the interstitial space of peripheral tissue compartments. Moreover, the present data report for the first time in healthy humans in vivo the true albumin concentrations of interstitial fluid of adipose tissue and skeletal muscle.     

Lipolysis in human adipose tissue during exercise: comparison of microdialysis and a-v measurements.

Subcutaneous adipose tissue lipolysis was studied in vivo by Fick's arteriovenous (a-v) principle using either calculated (microdialysis) or directly measured (catheterization) adipose tissue venous glycerol concentration. We compared results during steady-state (rest and prolonged continuous exercise), as well as during non-steady-state (onset of exercise and early exercise) experimental settings. Fourteen healthy women [age: 74 +/- 1 (SE) yr] were studied at rest and during 60-min continuous bicycling at 60% of peak O(2) uptake. Calculated and measured subcutaneous abdominal adipose tissue venous glycerol concentrations increased substantially from rest to exercise but were similar both at rest and during later stages of exercise. In contrast, during the initial approximately 40 min of exercise, calculated glycerol concentration was significantly lower (approximately 40%) than measured adipose tissue venous glycerol concentration. Despite several methodological limitations inherent to both techniques, the results strongly suggest that microdialysis and catheterization provide similar estimates of subcutaneous adipose tissue lipolysis in steady-state experimental settings like rest and continuous prolonged exercise. However, during shorter periods of exercise (<40 min), the results from the two techniques may differ quantitatively in the studied subjects. Caution should, therefore, be taken when lipolysis is evaluated, based on results obtained by the two techniques under non-steady-state conditions.     

In vivo human lipolytic activity in preperitoneal and subdivisions of subcutaneous abdominal adipose tissue

We studied eight normal-weight male subjects to examine whether the lipolytic rate of deep subcutaneous and preperitoneal adipose tissues differs from that of superficial abdominal subcutaneous adipose tissue. The lipolytic rates in the superficial anterior and deep posterior subcutaneous abdominal adipose tissues and in the preperitoneal adipose tissue in the round ligament were measured by microdialysis and (133)Xe washout under basal, postabsorptive conditions and during intravenous epinephrine infusion (0.15 nmol. kg(-1). min(-1)). Both in the basal state and during epinephrine stimulation, the superficial subcutaneous adipose tissue had higher interstitial glycerol concentrations than the two other depots. Similarly, the calculated glycerol outputs from the superficial depot were significantly higher than those from the deep subcutaneous and the preperitoneal depots. Thus, it is concluded that the lipolytic rate of the superficial subcutaneous adipose tissue on the anterior abdominal wall is higher than that of the deep subcutaneous adipose tissue on the posterior abdominal wall and that of the preperitoneal adipose tissue in the round ligament.     

Assessment of transcapillary glucose exchange in human skeletal muscle and adipose tissue

We studied the kinetics of glucose exchange between plasma and interstitial fluid (ISF) in human skeletal muscle and adipose tissue under fasting conditions. Five normal human subjects received an intravenous [6,6-2H2]glucose infusion in a prime-continuous fashion. During the tracer infusion, the open-flow microperfusion technique was employed to frequently sample ISF from quadriceps muscle and subcutaneous adipose tissue. The tracer glucose kinetics observed in muscle and adipose tissue ISF were found to be well described by a capillary-tissue exchange model. As a measure of transcapillary glucose exchange efficiency, the 95% equilibrium time was calculated from the identified model parameters. This time constant was similar for skeletal muscle and adipose tissue (28.6 +/- 3.2 vs. 26.8 +/- 3.6 min; P = 0.60). Furthermore, we found that the (total) interstitial glucose concentration was significantly lower (P < 0.01) in muscle (3.32 +/- 0.46 mmol/l) and adipose tissue (3.51 +/- 0.17 mmol/l) compared with arterialized plasma levels (5.56 +/- 0.13 mmol/l). Thus the observed gradients and dynamic relationships between plasma and ISF glucose in muscle and adipose tissue provide evidence that transcapillary exchange of glucose is limited in these two tissues under fasting conditions.     

Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women

We measured whole body and regional lipolytic and adipose tissue blood flow (ATBF) sensitivity to epinephrine in 8 lean [body mass index (BMI): 21 +/- 1 kg/m(2)] and 10 upper body obese (UBO) women (BMI: 38 +/- 1 kg/m(2); waist circumference >100 cm). All subjects underwent a four-stage epinephrine infusion (0.00125, 0.005, 0.0125, and 0.025 microgram. kg fat-free mass(-1). min(-1)) plus pancreatic hormonal clamp. Whole body free fatty acid (FFA) and glycerol rates of appearance (R(a)) in plasma were determined by stable isotope tracer methodology. Abdominal and femoral subcutaneous adipose tissue lipolytic activity was determined by microdialysis and (133)Xe clearance methods. Basal whole body FFA R(a) and glycerol R(a) were both greater (P < 0.05) in obese (449 +/- 31 and 220 +/- 12 micromol/min, respectively) compared with lean subjects (323 +/- 44 and 167 +/- 21 micromol/min, respectively). Epinephrine infusion significantly increased FFA R(a) and glycerol R(a) in lean (71 +/- 21 and 122 +/- 52%, respectively; P < 0.05) but not obese subjects (7 +/- 6 and 39 +/- 10%, respectively; P = not significant). In addition, lipolytic and ATBF sensitivity to epinephrine was blunted in abdominal but not femoral subcutaneous adipose tissue of obese compared with lean subjects. We conclude that whole body lipolytic sensitivity to epinephrine is blunted in women with UBO because of decreased sensitivity in upper body but not lower body subcutaneous adipose tissue.     

Metabolic and Hemodynamic Response of Adipose Tissue to Angiotensin II

Objective: Recent studies have revealed the presence of a local renin‐angiotensin system in adipose tissue. To examine the possible role of this system in adipose tissue, we performed microdialysis studies on the effect of angiotensin II (Ang II) on blood flow and metabolism in abdominal subcutaneous adipose tissue (aSAT) and femoral subcutaneous adipose tissue (fSAT) in young healthy men. Research Methods and Procedures: Using the microdialysis technique, two different protocols were run perfusion with Ringer's solution + 50 mM ethanol with the subsequent addition of 125, 250, and 500 μg/liter Ang II (n = 8) and Ringers's solution + 50 mM ethanol with the subsequent addition of isoproterenol (1 μM) alone and in combination with 500 μg/liter Ang II (n = 6). Dialysate concentrations of ethanol, glycerol, glucose, and lactate were measured for estimating blood flow (ethanol dilution technique), lipolysis, and glycolysis, respectively. Results: Perfusion with Ang II resulted in a dose‐dependent decrease in blood flow (fSAT > aSAT), lipolysis (fSAT > aSAT), and glucose uptake (fSAT = aSAT). Isoproterenol increased blood flow and lipolysis at both sites and those effects could be returned to baseline values by the addition of Ang II in aSAT but not fSAT. Discussion: In conclusion, our data indicate that in addition to its well‐known vasoconstricting effect, Ang II inhibits lipolysis in adipose tissue, whereby femoral fat depots seem to be more sensitive to this effect than abdominal depots.     

In-vivo behaviour of hypodermically implanted microfabricated glucose sensors

The in-vivo behaviour of microfabricated GOD (glucose oxidase)/H2O2 glucose sensor implanted subcutaneously in normal anaesthetized rats has been studied. The sensor consists of a planar, three-electrode microcell, an enzyme membrane (glucose oxidase and bovine serum albumin cross-linked with glutaraldehyde) and an outer diffusion limiting polyurethane membrane. The sensor behaviour during hyperglycaemic (13.8 mM and 11.2 mM), euglycaemic (7.8 mM) and hypoglycaemic (3.5 mM) plateau levels was determined. The values of the in-vivo sensitivity (0.64 +/- 0.05 nA/mM) and background current (1.25 +/- 0.4 nA) were determined using a two-point calibration method and then used to calculate apparent subcutaneous glucose concentrations. The results show the presence of a good correlation between all the plasma glucose levels (G) and the apparent subcutaneous tissue concentrations (G'), with G' = 0.997.G - 0.066, r = 0.9782.     

Influences of AT1 receptor blockade on tissue metabolism in obese men

ANG II applied to the interstitial space influences carbohydrate and lipid metabolism in a tissue-specific fashion. Thus endogenous ANG II may have a tonic effect on tissue metabolism that could be reversed with ANG II type 1 (AT1) receptor blockade, particularly during adrenergic stimulation. We studied 14 obese men. They were treated for 10 days with the AT1 receptor blocker irbesartan or with placebo in a double-blind and crossover fashion. At the end of each treatment period, we assessed skeletal muscle and adipose tissue metabolism using the microdialysis technique. The ethanol dilution technique was applied to follow changes in tissue blood flow. Measurements were obtained at baseline and during application of incremental isoproterenol concentrations through the microdialysis catheter. Blood pressure decreased from 133 +/- 3/84 +/- 3 to 128 +/- 3/79 +/- 2 mmHg for systolic and diastolic blood, respectively (P = 0.02 and 0.006, respectively) with AT1 receptor blockade. Isoproterenol perfusion caused a dose-dependent increase in dialysate glycerol in adipose tissue and in skeletal muscle. Irbesartan slightly reduced the isoproterenol-induced glycerol response in adipose tissue (P < 0.05 by ANOVA). Ethanol ratio, interstitial glucose supply, and lactate production in adipose tissue and skeletal muscle were similar with placebo and irbesartan. We conclude that AT1 receptor blockade in obese men does not reveal a major tonic ANG II effect on interstitial glucose supply, lipolysis, or glycolysis in skeletal muscle, either at rest or during beta-adrenergic stimulation. Endogeneous ANG II may slightly increase adipose tissue lipolysis. The mechanism may promote the redistribution of triglycerides from adipose tissue toward other organs.     

Blood flow in subcutaneous adipose tissue depends on skin-fold thickness.

Blood flow in subcutaneous adipose tissue is reduced in obese compared to lean subjects. Limitations in vascular supply might interfere with adipose tissue function as a metabolic and endocrine organ. We tested the hypothesis that nutritive blood flow and tissue metabolism depends on subcutaneous adipose tissue thickness even in normal-weight subjects. Sixteen young, healthy, normal-weight subjects (8 men, 8 women) were included in the study. Abdominal subcutaneous adipose thickness was assessed by skin-fold measurements. The microdialysis technique was applied for monitoring basal adipose tissue blood flow (ethanol dilution technique) and metabolism. An increase in skin-fold thickness from 15 to 45 mm and from 8 to 37 mm was associated with a linear increase in basal ethanol ratio from 0.19 to 0.63 and 0.25 to 0.75 and linear decreases in dialysate glucose concentrations from 1.95 to 0.24 mM and 1.68 to 0.29 mM, and 152 to 42 microM and 172 to 49 microM for glycerol concentrations in men and women, respectively (p < 0.05). Isoproterenol-stimulated blood flow also inversely correlated to skin-fold thickness (p < 0.05). We conclude that increased adipose tissue thickness is associated with reduced tissue perfusion and metabolism, even in lean subjects. Skin-fold thickness is an important confounding variable in metabolic studies, particularly in microdialysis experiments.     

Fat metabolism and acute resistance exercise in trained men.

The purpose of this study was to investigate the effect of acute resistance exercise (RE) on lipolysis within adipose tissue and subsequent substrate oxidation to better understand how RE may contribute to improvements in body composition. Lipolysis and blood flow were measured in abdominal subcutaneous adipose tissue via microdialysis before, during, and for 5 h following whole body RE as well as on a nonexercise control day (C) in eight young (24 +/- 0.7 yr), active (>3 RE session/wk for at least 2 yr) male participants. Fat oxidation was measured immediately before and after RE via indirect calorimetry for 45 min. Dialysate glycerol concentration (an index of lipolysis) was higher during (RE: 200.4 +/- 38.6 vs. C: 112.4 +/- 13.1 micromol/l, 78% difference; P = 0.02) and immediately following RE (RE: 184 +/- 41 vs. C: 105 + 14.6 micromol/l, 75% difference; P = 0.03) compared with the same time period on the C day. Energy expenditure was elevated in the 45 min after RE compared with the same time period on the C day (RE: 104.4 +/- 6.0 vs. C: 94.5 +/- 4.0 kcal/h, 10.5% difference; P = 0.03). Respiratory exchange ratio was lower (RE: 0.71 +/- 0.004 vs. C: 0.85 +/- .03, 16.5% difference; P = 0.004) and fat oxidation was higher (RE: 10.2 +/- 0.8 vs. C: 5.0 +/- 1.0 g/h, 105% difference; P = 0.004) following RE compared with the same time period on the C day. Therefore, the mechanism behind RE contributing to improved body composition is in part due to enhanced abdominal subcutaneous adipose tissue lipolysis and improved whole body fat oxidation and energy expenditure in response to RE.