Lack of alpha(2)-adrenergic antilipolytic effect during exercise in subcutaneous adipose tissue of trained men.

The aim of this study was to investigate the involvement of the antilipolytic alpha(2)-adrenergic receptor pathway in the regulation of lipolysis during exercise in subcutaneous abdominal adipose tissue (SCAAT). Seven trained men and 15 untrained men were studied. With the use of microdialysis, the extracellular glycerol concentration was measured in SCAAT at rest and during 60 min of exercise at 50% of maximal oxygen consumption. One microdialysis probe was perfused with Ringer solution; the other was supplemented with phentolamine (alpha(2)-adrenergic receptor antagonist). No differences in baseline extracellular or plasma glycerol concentrations were found between the two groups. The exercise-induced extracellular and plasma glycerol increase was higher in trained compared with untrained subjects (P < 0.05). Addition of phentolamine to the perfusate enhanced the exercise-induced response of extracellular glycerol in untrained subjects but not in trained subjects. The exercise-induced increase in plasma norepinephrine and epinephrine concentrations and the decrease in plasma insulin were not different in the two groups. These in vivo findings demonstrate higher exercise-induced lipolysis in trained compared with untrained subjects and show that, in trained subjects, the alpha(2)-mediated antilipolytic action is not involved in the regulation of lipolysis in SCAAT during exercise.     

Atrial natriuretic peptide stimulates lipid mobilization during repeated bouts of endurance exercise

Atrial natriuretic peptide (ANP) controls lipolysis in human adipocytes. Lipid mobilization is increased during repeated bouts of exercise, but the underlying mechanisms involved in this process have not yet been delineated. The relative involvement of catecholamine- and ANP-dependent pathways in the control of lipid mobilization during repeated bouts of exercise was thus investigated in subcutaneous adipose tissue (SCAT) by microdialysis. The study was performed in healthy males. Subjects performed two 45-min exercise bouts (E1 and E2) at 50% of their maximal oxygen uptake separated by a 60-min rest period. Extracellular glycerol concentration (EGC), reflecting SCAT lipolysis, was measured in a control probe perfused with Ringer solution and in two other probes perfused with either Ringer plus phentolamine (alpha(1/2)-AR antagonist) or Ringer plus both phentolamine and propranolol (beta-AR antagonist). Plasma epinephrine, plasma glycerol, and EGC were 1.7-, 1.6-, and 1.2-fold higher in E2 than in E1, respectively. Phentolamine potentiated exercise-induced EGC increase during E2 only. Propranolol reduced the lipolytic rate during both E1 and E2 compared with the probe with phentolamine. Plasma ANP concentration increased more during E2 than during E1 and was correlated with the increase in EGC in the probe containing phentolamine plus propranolol. The results suggest that ANP is involved in the control of lipolysis during exercise and that it contributes to stimulation of lipolysis during repeated bouts of exercise.     

Acute exposure to long-chain fatty acids impairs {alpha}2-adrenergic receptor-mediated antilipolysis in human adipose tissue

The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 mumol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic alpha(2)-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an alpha-antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the alpha(2)-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the alpha(2)-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress alpha(2)-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis.     

Exercise-induced lipid mobilization in subcutaneous adipose tissue is mainly related to natriuretic peptides in overweight men

Involvement of sympathetic nervous system and natriuretic peptides in the control of exercise-induced lipid mobilization was compared in overweight and lean men. Lipid mobilization was determined using local microdialysis during exercise. Subjects performed 35-min exercise bouts at 60% of their maximal oxygen consumption under placebo or after oral tertatolol [a beta-adrenergic receptor (AR) antagonist]. Under placebo, exercise increased dialysate glycerol concentration (DGC) in both groups. Phentolamine (alpha-AR antagonist) potentiated exercise-induced lipolysis in overweight but not in lean subjects; the alpha(2)-antilipolytic effect was only functional in overweight men. After tertatolol administration, the DGC increased similarly during exercise no matter which was used probe in both groups. Compared with the control probe under placebo, lipolysis was reduced in lean but not in overweight men treated with the beta-AR blocker. Tertatolol reduced plasma nonesterified fatty acids and insulin concentration in both groups at rest. Under placebo or tertatolol, the exercise-induced changes in plasma nonesterified fatty acids, glycerol, and insulin concentrations were similar in both groups. Exercise promoted a higher increase in catecholamine and ANP plasma levels after tertatolol administration. In conclusion, the major finding of our study is that in overweight men, in addition to an increased alpha(2)-antilipolytic effect, the lipid mobilization in subcutaneous adipose tissue that persists during exercise under beta-blockade is not dependent on catecholamine action. On the basis of correlation findings, it seems to be related to a concomitant exercise-induced rise in plasma ANP when exercise is performed under tertatolol intake and a decrease in plasma insulin.     

Excess body fat in men decreases plasma fatty acid availability and oxidation during endurance exercise

The effect of relative body fat mass on exercise-induced stimulation of lipolysis and fatty acid oxidation was evaluated in 15 untrained men (5 lean, 5 overweight, and 5 obese with body mass indexes of 21 +/- 1, 27 +/- 1, and 34 +/- 1 kg/m2, respectively, and %body fat ranging from 12 to 32%). Palmitate and glycerol kinetics and substrate oxidation were assessed during 90 min of cycling at 50% peak aerobic capacity (VO2 peak) by use of stable isotope-labeled tracer infusion and indirect calorimetry. An inverse relationship was found between %body fat and exercise-induced increase in glycerol appearance rate relative to fat mass (r2 = 0.74; P < 0.01). The increase in total fatty acid uptake during exercise [(micromol/kg fat-free mass) x 90 min] was approximately 50% smaller in obese (181 +/- 70; P < 0.05) and approximately 35% smaller in overweight (230 +/- 71; P < 0.05) than in lean (354 +/- 34) men. The percentage of total fatty acid oxidation derived from systemic plasma fatty acids decreased with increasing body fat, from 49 +/- 3% in lean to 39 +/- 4% in obese men (P < 0.05); conversely, the percentage of nonsystemic fatty acids, presumably derived from intramuscular and possibly plasma triglycerides, increased with increasing body fat (P < 0.05). We conclude that the lipolytic response to exercise decreases with increasing adiposity. The blunted increase in lipolytic rate in overweight and obese men compared with lean men limits the availability of plasma fatty acids as a fuel during exercise. However, the rate of total fat oxidation was similar in all groups because of a compensatory increase in the oxidation of nonsystemic fatty acids.     

Sex differences in lipolysis-regulating mechanisms in overweight subjects: effect of exercise intensity

Objective: To explore sex differences in the regulation of lipolysis during exercise, the lipid‐mobilizing mechanisms in the subcutaneous adipose tissue (SCAT) of overweight men and women were studied using microdialysis. Research Methods and Procedures: Subjects matched for age, BMI, and physical fitness performed two 30‐minute exercise bouts in a randomized fashion: the first test at 30% and 50% of their individual maximal oxygen uptake (Vo _2max) and the second test at 30% and 70% of their Vo _2max. Results: In both groups, an exercise‐dependent increment in extracellular glycerol concentration (EGC) was observed. Whatever the intensity, phentolamine [α‐adrenergic receptor (AR) antagonist] added to a dialysis probe potentiated exercise‐induced lipolysis only in men. In a probe containing phentolamine plus propranolol (β‐AR antagonist), no changes in EGC occurred when compared with the control probe when exercise was performed at 30% and 50% Vo _2max. A significant reduction of EGC (when compared with the control probe) was observed in women at 70% Vo _2max. At each exercise power, the plasma non‐esterified fatty acid and glycerol concentrations were higher in women. Exercise‐induced increase in plasma catecholamine levels was lower in women compared with men. Plasma insulin decreased and atrial natriuretic peptide increased similarly in both groups. Discussion: Overweight women mobilize more lipids (assessed by glycerol) than men during exercise. α₂‐Anti‐lipolytic effect was functional in SCAT of men only. The major finding is that during low‐to‐moderate exercise periods (30% and 50% Vo _2max), lipid mobilization in SCAT relies less on catecholamine‐dependent stimulation of β‐ARs than on an increase in plasma atrial natriuretic peptide concentrations and the decrease in plasma insulin.     

VLDL-triglyceride kinetics during hyperglycemia-hyperinsulinemia: effects of sex and obesity

We have previously shown that sex and obesity independently affect basal very low density lipoprotein (VLDL)-triglyceride (TG) kinetics. In the present study, we investigated the effect of hyperglycemia-hyperinsulinemia on VLDL-TG kinetics in lean and obese men and women (n = 6 in each group). VLDL-TG kinetics were measured during basal, postabsorptive conditions and during glucose infusion (5.5 mg x kg FFM(-1) x min(-1)) by using [(2)H(5)]glycerol bolus injection in conjunction with compartmental modeling analysis. Basal VLDL-TG secretion in plasma was greater in obese than in lean men (7.8 +/- 0.6 and 2.9 +/- 0.4 micromol x l plasma(-1) x min(-1); P < 0.001) but was not different in lean and obese women (5.0 +/- 1.1 and 5.9 +/- 1.1 micromol x l plasma(-1) x min(-1)). Glucose infusion decreased the VLDL-TG secretion rate by approximately 50% in lean and obese men and in lean women (to 1.5 +/- 0.4, 4.0 +/- 0.6, and 2.2 +/- 0.4 micromol x l plasma(-1) x min(-1), respectively; all P < 0.05) but had no effect on the VLDL-TG secretion rate in obese women (4.9 +/- 1.0 micromol x l plasma(-1) x min(-1)). These results demonstrate that both sex and adiposity affect the regulation of VLDL-TG metabolism. Glucose and insulin decrease VLDL-TG production in both lean men and lean women; obesity is associated with resistance to the glucose- and insulin-mediated suppression of VLDL-TG secretion in women, but not in men.     

Oxidation of nonplasma fatty acids during exercise is increased in women with abdominal obesity.

We evaluated plasma fatty acid availability and plasma and whole body fatty acid oxidation during exercise in five lean and five abdominally obese women (body mass index = 21 +/- 1 vs. 38 +/- 1 kg/m(2)), who were matched on aerobic fitness, to test the hypothesis that obesity alters the relative contribution of plasma and nonplasma fatty acids to total energy production during exercise. Subjects exercised on a recumbent cycle ergometer for 90 min at 54% of their peak oxygen consumption. Stable isotope tracer methods ([(13)C]palmitate) were used to measure fatty acid rate of appearance in plasma and the rate of plasma fatty acid oxidation, and indirect calorimetry was used to measure whole body substrate oxidation. During exercise, palmitate rate of appearance increased progressively and was similar in obese and lean groups between 60 and 90 min of exercise [3.9 +/- 0.4 vs. 4.0 +/- 0.3 micromol. kg fat free mass (FFM)(-1). min(-1)]. The rate of plasma fatty acid oxidation was also similar in obese and lean subjects (12.8 +/- 1.7 vs. 14.5 +/- 1.8 micromol. kg FFM(-1). min(-1); P = not significant). However, whole body fatty acid oxidation during exercise was 25% greater in obese than in lean subjects (21.9 +/- 1.2 vs. 17.5 +/- 1.6 micromol. kg FFM(-1). min(-1); P < 0.05). These results demonstrate that, although plasma fatty acid availability and oxidation are similar during exercise in lean and obese women, women with abdominal obesity use more fat as a fuel by oxidizing more nonplasma fatty acids.     

Adipose tissue lipolysis is increased during a repeated bout of aerobic exercise.

The goal of the study was to examine whether lipid mobilization from adipose tissue undergoes changes during repeated bouts of prolonged aerobic exercise. Microdialysis of the subcutaneous adipose tissue was used for the assessment of lipolysis; glycerol concentration was measured in the dialysate leaving the adipose tissue. Seven male subjects performed two repeated bouts of 60-min exercise at 50% of their maximal aerobic power, separated by a 60-min recovery period. The exercise-induced increases in extracellular glycerol concentrations in adipose tissue and in plasma glycerol concentrations were significantly higher during the second exercise bout compared with the first (P < 0.05). The responses of plasma nonesterified fatty acids and plasma epinephrine were higher during the second exercise bout, whereas the response of norepinephrine was unchanged and that of growth hormone lower. Plasma insulin levels were lower during the second exercise bout. The results suggest that adipose tissue lipolysis during aerobic exercise of moderate intensity is enhanced when an exercise bout is preceded by exercise of the same intensity and duration performed 1 h before. This response pattern is associated with an increase in the exercise-induced rise of epinephrine and with lower plasma insulin values during the repeated exercise bout.     

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.     

Activation of alpha2-adrenergic receptors blunts epinephrine-induced lipolysis in subcutaneous adipose tissue during a hyperinsulinemic euglycemic clamp in men

The aim of this study was to investigate whether hyperinsulinemia modifies adrenergic control of lipolysis, with particular attention paid to the involvement of antilipolytic alpha2-adrenergic receptors (AR). Eight healthy male subjects (age: 23.9 +/- 0.9 yr; body mass index: 23.8 +/- 1.9) were investigated during a 6-h euglycemichyperinsulinemic clamp and in control conditions. Before and during the clamp, the effect of graded perfusions of isoproterenol (0.1 and 1 microM) or epinephrine (1 and 10 microM) on the extracellular glycerol concentration in subcutaneous abdominal adipose tissue was evaluated by using the microdialysis method. Both isoproterenol and epinephrine induced a dose-dependent increase in extracellular glycerol concentration when infused for 60 min through the microdialysis probes before and during hours 3 and 6 of the clamp. The catecholamine-induced increase was significantly lower during the clamp than before it, with the inhibition being more pronounced in hour 6 of the clamp. Isoproterenol (1 microM)-induced lipolysis was reduced by 28 and 44% during hours 3 and 6 of the clamp, respectively, whereas the reduction of epinephrine (100 microM)-induced lipolysis was significantly greater (by 63 and 70%, P < 0.01 and P < 0.04, respectively) during the same time intervals. When epinephrine was infused in combination with 100 microM phentolamine (a nonselective alpha-AR antagonist), the inhibition of epinephrine (10 microM)-induced lipolysis was only of 19 and 40% during hours 3 and 6 of the clamp, respectively. The results demonstrate that, in situ, insulin counteracts the epinephrine-induced lipolysis in adipose tissue. The effect involves 1) reduction of lipolysis stimulation mediated by the beta-adrenergic pathway and 2) the antilipolytic component of epinephrine action mediated by alpha2-ARs.     

Aerobic training improves exercise-induced lipolysis in SCAT and lipid utilization in overweight men

The aim of this study was to investigate whether endurance training improves lipid mobilization and oxidation in overweight subjects. Eleven young men (25.6 +/- 1.4 yr and body mass index 27.7 +/- 0.2) performed a 4-mo training program consisting of practicing aerobic exercise 5 days/wk. Before and after the training period, lipid oxidation was explored during a 60-min exercise at 50% of peak O2 consumption by use of indirect calorimetry. Lipid mobilization and antilipolytic alpha2-adrenoceptor effect were also studied using the microdialysis method in abdominal subcutaneous adipose tissue (SCAT). After training, plasma nonesterified fatty acid (NEFA) levels, at rest and during exercise, were significantly lower than before (P < 0.001). Lipolysis in SCAT was significantly higher after than before training. An antilipolytic alpha2-adrenoceptor effect in SCAT was underlined during exercise before training and disappeared after. The respiratory exchange ratio was lower after training, i.e., the percentage of lipid oxidation was higher only at rest. The amount of lipid oxidized was higher after training, at rest, and during exercise. Although exercise power was higher after training, the relative intensity was equivalent, as suggested by a similar increase in plasma catecholamine concentrations before and after training. In conclusion, 4-mo training in overweight men improved lipid mobilization through a decrease of antilipolytic alpha2-adrenoceptor effect in SCAT and lipid oxidation during moderate exercise. Training induced a decrease of blood NEFA, predicting better prevention of obesity.     

Influence of lipolysis and fatty acid availability on fuel selection during exercise

The aim of the present study was to investigate the influence of substrate availability on fuel selection during exercise. Eight endurance-trained male cyclists performed 90-min exercise at 70 % of their maximal oxygen uptake in a cross-over design, either in rested condition (CON) or the day after 2-h exercise practised at 70 % of maximal oxygen uptake (EX). Subjects were given a sucrose load (0.75 g kg^?1 body weight) 45 min after the beginning of the 90-min exercise test. Lipolysis was measured in subcutaneous abdominal adipose tissue (SCAT) by microdialysis and substrate oxidation by indirect calorimetry. Lipid oxidation increased during exercise and tended to decrease during sucrose ingestion in both conditions. Lipid oxidation was higher during the whole experimental period in the EX group (p?=?0.004). Interestingly, fuel selection, assessed by the change in respiratory exchange ratio (RER), was increased in the EX session (p?=?0.002). This was paralleled by a higher rate of SCAT lipolysis reflected by dialysate glycerol, plasma glycerol, and fatty acids (FA) levels (p?<?0.001). Of note, we observed a significant relationship between whole-body fat oxidation and dialysate glycerol in both sessions (r ²?=?0.33, p?=?0.02). In conclusion, this study highlights the limiting role of lipolysis and plasma FA availability to whole-body fat oxidation during exercise in endurance-trained subjects. This study shows that adipose tissue lipolysis is a determinant of fuel selection during exercise in healthy subjects.     

Effects of plasma epinephrine on fat metabolism during exercise: interactions with exercise intensity

This study determined the effects of elevated plasma epinephrine on fat metabolism during exercise. On four occasions, seven moderately trained subjects cycled at 25% of peak oxygen consumption (VO(2 peak)) for 60 min. After 15 min of exercise, subjects were intravenously infused with low (0.96 +/- 0.10 nM), moderate (1.92 +/- 0.24 nM), or high (3.44 +/- 0.50 nM) levels (all P < 0.05) of epinephrine to increase plasma epinephrine above control (Con; 0.59 +/- 0.10 nM). During the interval between 35 and 55 min of exercise, lipolysis [i.e., rate of appearance of glycerol] increased above Con (4.9 +/- 0.5 micromol. kg(-1). min(-1)) with low, moderate, and high (6.5 +/- 0.5, 7.1 +/- 0.8, and 10.6 +/- 1.2 micromol. kg(-1). min(-1), respectively; all P < 0.05) levels of epinephrine despite simultaneous increases in plasma insulin. The release of fatty acid into plasma also increased progressively with the graded epinephrine infusions. However, fatty acid oxidation was lower than Con (11.1 +/- 0.8 micromol. kg(-1). min(-1)) during moderate and high levels (8.7 +/- 0.7 and 8.1 +/- 0.9 micromol. kg(-1). min(-1), respectively; P < 0.05). In one additional trial, the same subjects exercised at 45% VO(2 peak) without epinephrine infusion, which produced a plasma epinephrine concentration identical to low levels. However, lipolysis was lower (i.e., 5.5 +/- 0.6 vs. 6.5 +/- 0.5 micromol. kg(-1). min(-1); P < 0.05). In conclusion, elevations in plasma epinephrine concentration during exercise at 25% of VO(2 peak) progressively increase whole body lipolysis but decrease fatty acid oxidation. Last, increasing exercise intensity from 25 to 45% VO(2 peak) attenuates the lipolytic actions of epinephrine.     

Adrenergic control of lipolysis and metabolic responses in obesity

Adrenergic modulation of lipolysis was determined in obese and lean women. Epinephrine was infused alone, or in combination with propranolol, or with phentolamine. In both obese and lean subjects slight alpha- and prevalent beta-adrenergic lipolytic responsiveness was observed. alpha-adrenergic blockade by yohimbine potentiated lipolysis and exercise energy expenditure. Yohimbine application during the slimming treatment increased weight loss without side effects.     

Atrial natriuretic peptide contribution to lipid mobilization and utilization during head-down bed rest in humans

Head-down bed rest (HDBR) increases plasma levels of atrial natriuretic peptide (ANP) and decreases norepinephrine levels. We previously demonstrated that ANP promotes lipid mobilization and utilization, an effect independent of sympathetic nervous system activation, when infused into lean healthy men at pharmacological doses. The purpose of the present study was to demonstrate that a physiological increase in ANP contributes to lipid mobilization and oxidation in healthy young men. Eight men were positioned for 4 h in a sitting (control) or in a HDBR position. Indexes of lipid mobilization and hormonal changes were measured in plasma. Extracellular glycerol, an index of lipolysis, was determined in subcutaneous adipose tissue (SCAT) with a microdialysis technique. A twofold increase in plasma ANP concentration was observed after 60 min of HDBR, and a plateau was maintained thereafter. Plasma norepinephrine decreased by 30-40% during HDBR, while plasma insulin and glucose levels did not change. The level of plasma nonesterified fatty acids was higher during HDBR. SCAT lipolysis, as reflected by interstitial glycerol, as well as interstitial cGMP, the second messenger of the ANP pathway, increased during HDBR. This was associated with an increase in blood flow observed throughout HDBR. Significant changes in respiratory exchange ratio and percent use of lipid and carbohydrate were seen only after 3 h of HDBR. Thus the proportion of lipid oxidized increased by 40% after 3 h of HDBR. The rise in plasma ANP during HDBR was associated with increased lipolysis in SCAT and whole body lipid oxidation. In this physiological setting, independent of increasing catecholamines, our study suggests that ANP contributes to lipid mobilization and oxidation in healthy young men.     

Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans

Cortisol's effects on lipid metabolism are controversial and may involve stimulation of both lipolysis and lipogenesis. This study was undertaken to define the role of physiological hypercortisolemia on systemic and regional lipolysis in humans. We investigated seven healthy young male volunteers after an overnight fast on two occasions by means of microdialysis and palmitate turnover in a placebo-controlled manner with a pancreatic pituitary clamp involving inhibition with somatostatin and substitution of growth hormone, glucagon, and insulin at basal levels. Hydrocortisone infusion increased circulating concentrations of cortisol (888 +/- 12 vs. 245 +/- 7 nmol/l). Interstitial glycerol concentrations rose in parallel in abdominal (327 +/- 35 vs. 156 +/- 30 micromol/l; P = 0.05) and femoral (178 +/- 28 vs. 91 +/- 22 micromol/l; P = 0.02) adipose tissue. Systemic [(3)H]palmitate turnover increased (165 +/- 17 vs. 92 +/- 24 micromol/min; P = 0.01). Levels of insulin, glucagon, and growth hormone were comparable. In conclusion, the present study unmistakably shows that cortisol in physiological concentrations is a potent stimulus of lipolysis and that this effect prevails equally in both femoral and abdominal adipose tissue.     

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.     

Catecholamine and insulin control of lipolysis in subcutaneous adipose tissue during long-term diet-induced weight loss in obese women

The aim of this study was to investigate the evolution of the adrenergic and insulin-mediated regulation of lipolysis during different phases of a 6-mo dietary intervention. Eight obese women underwent a 6-mo dietary intervention consisting of a 1-mo very low-calorie diet (VLCD) followed by a 2-mo low-calorie diet (LCD) and 3-mo weight maintenance (WM) diet. At each phase of the dietary intervention, microdialysis of subcutaneous adipose tissue (SCAT) was performed at rest and during a 3-h hyperinsulinemic euglycemic clamp. Responses of dialysate glycerol concentration (DGC) were determined at baseline and during local perfusions with adrenaline or adrenaline and phentolamine before and during the last 30 min of the clamp. Dietary intervention induced a body weight reduction and an improved insulin sensitivity. DGC progressively decreased during the clamp, and this decrease was similar during the different phases of the diet. The adrenaline-induced increase in DGC was higher at VLCD and LCD compared with baseline condition and returned to prediet levels at WM. In the probe with adrenaline and phentolamine, the increase in DGC was higher than that in the adrenaline probe at baseline and WM, but it was not different at VLCD and LCD. The results suggest that the responsiveness of SCAT to adrenaline-stimulated lipolysis increases during the calorie-restricted phases due to a reduction of the α(2)-adrenoceptor-mediated antilipolytic action of adrenaline. At WM, adrenaline-stimulated lipolysis returned to the prediet levels. Furthermore, no direct relationship between insulin sensitivity and the diet-induced changes in the regulation of lipolysis was found.     

Lipolysis and lipid oxidation in cirrhosis and after liver transplantation

On the basis of the finding that plasma glycerol concentration is not controlled by clearance in healthy humans, it has been proposed that elevated plasma free fatty acid (FFA) and glycerol concentrations in cirrhotic subjects are caused by accelerated lipolysis. This proposal has not been validated. We infused 10 volunteers, 10 cirrhotic subjects, and 10 patients after orthotopic liver transplantation (OLT) with [1-(13)C]palmitate and [(2)H(5)]glycerol to compare fluxes (R(a)) and FFA oxidation. Cirrhotic subjects had higher plasma palmitate (52%) and glycerol (33%) concentrations than controls. Palmitate R(a) was faster (1.45+/-0.18 vs. 0.85+/-0.17 micromol x kg(-1) x min(-1)) but glycerol R(a) and clearance slower (1.20+/-0.09 vs. 1.90+/-0.24 micromol x kg(-1) x min(-1) and 21.2+/-1.2 vs. 44.7+/- 4.9 ml x kg(-) x h(-1), respectively) than in controls. After OLT, plasma palmitate and glycerol concentrations and palmitate R(a) did not differ, but glycerol R(a) (1.16+/-0.11 micromol x kg(-1) x min(-1)) and clearance (26.7+/-2.4 ml x kg(-1) x h(-1)) were slower than in controls. We conclude that 1) impaired reesterification, not accelerated lipolysis, elevates FFA in cirrhotic subjects; 2) normalized FFA after OLT masks impaired reesterification; and 3) plasma glycerol concentration poorly reflects lipolytic rate in cirrhosis and after OLT.