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Biomedical subjects

P Arner

Publications and source records attributed to P Arner.

At least 163 records · Page 9Linked to original sources
PubMed1993

Influence of insulin on glucose metabolism and lipolysis in adipose tissue in situ in patients with liver cirrhosis.

The influence of insulin on lipolysis and glucose metabolism in abdominal adipose tissue was studied in situ with the microdialysis technique during a euglycaemic insulin clamp (1 mU kg-1 min-1) in nine cirrhotic patients and 10 controls. The cirrhotic patients displayed a 50% decrease in glucose utilization rate during the clamp (P < 0.001). Dialysate glucose levels decreased similarly by 20-30%., in patients and controls, which in the presence of unchanged local blood flow in the adipose tissue in response to insulin, is at hand with a glucose uptake into the adipocytes of similar magnitude in both groups. Before and during the clamp, the arterial and dialysate levels of glycerol were higher in the patients than in the control subjects (ANOVA P = 0.001 and 0.048 in arterial blood and dialysate, respectively). In relative terms, however, insulin induced a 70% reduction of arterial and dialysate glycerol in both groups. The concentrations of lactate and pyruvate in the dialysate and blood increased in a similar way in both groups during hyperinsulinaemia. The results suggest an increased rate of lipolysis in cirrhotic patients. Insulin cannot lower it to normal, although it is still capable of achieving a relative reduction. No explanation was found in the adipose tissue to the insulin resistance to whole-body glucose utilization that was noted in the patients with cirrhosis.

Adipose Tissue↗
PubMed1993

Evidence for a functional beta 3-adrenoceptor in man.

1. The existence of a functional beta 3-adrenoceptor in man was investigated by studying the lipolytic action of selective beta-adrenoceptor agents in isolated white omental and subcutaneous fat cells. 2. The non-selective beta 1/beta 2-adrenoceptor antagonist, CGP 12177 was lipolytic in both omental and subcutaneous fat cells. The intrinsic activity relative to isoprenaline was greater in omental than in subcutaneous cells. 3. Addition of the beta 2-adrenoceptor antagonist, ICI 118,551 and the beta 1-adrenoceptor antagonist CGP 20712A in combination or the non-selective beta-adrenoceptor antagonist propranolol alone (all 10(-7) M), induced a rightward shift of the dose-response curves for isoprenaline- and BRL37344-stimulated lipolysis of about 4 and 2 log-units, respectively. However, the antagonists did not alter lipolysis induced by CGP12177. 4. Several concentrations of beta-adrenoceptor antagonists were used to determine the pA2 values by Schild analysis. The values for CGP 20712A and ICI 118,551 (6.63 +/- 0.20 and 6.25 +/- 0.12) as antagonists of the lipolytic effects of CGP 12177 were over 2 units lower than the pA2 value for CGP 20712A against the response to the selective beta 1-agonist dobutamine (8.58 +/- 0.23) and the pA2 value for ICI 118,551 against the response to the selective beta 2-agonist terbutaline (9.15 +/- 0.26). 5. beta 3-Adrenoceptor mRNA expression, investigated with a polymerase chain reaction assay, was demonstrated in both types of adipocytes in the same cell preparations that had a lipolytic response to CGP 12177. 6. In conclusion, human white fat cells express an atypical beta-adrenoceptor in addition to beta 1- and beta 2-adrenoceptors. This receptor is stimulated more selectively by the beta1/beta2-antagonist CGP 12177 than by BRL 37344 and is poorly sensitive to blockade by selective beta1- and beta2-antagonists. On the basis of the pharmacological properties and the mRNA analyses, we suggest that this atypical receptor corresponds to the beta 3-adrenoceptor subtype.

Adipocytes↗
PubMed1993

Lack of lipolytic response in infants after endotracheal intubation.

The sympathoadrenal response to endotracheal intubation was investigated in nine infants 2-4 months old and in eight adults 23-45 years old at the start of inguinal hernia operations. In both infants and adults, heart rate and diastolic blood pressure increased significantly immediately after intubation. In both groups, moreover, there was a mean (SD) reduction in microvascular blood flow in the abdominal skin (infants -21 (14)%, adults -14 (7)%) and in the adipose tissue (infants -7 (4)%, adults -5 (4)%). However, the plasma glycerol concentration did not increase in the infants whereas it increased in the adults by 50 (12)%. In conclusion, infants and adults showed similar circulatory reactions during endotracheal intubation but the markedly increased lipolysis rate observed in adults was not seen in the infants. This may indicate that catecholamine induced lipolysis in vivo as well as in vitro is poor during infancy.

Adult↗
PubMed1993

Adipocyte beta-adrenoceptor sensitivity influences plasma lipid levels.

Catecholamine stimulation of lipolysis through adipocyte beta-adrenoceptors is of major importance for the regulation of lipid mobilization from adipose tissue. The influence of adipocyte beta-receptor sensitivity as assessed by an isoprenaline bioassay on circulating lipid levels was investigated in 46 healthy and drug-free subjects. beta-Receptor sensitivity was inversely related to total plasma triglycerides (r = -.62), very low density lipoprotein cholesterol (VLDL-C) (r = -.56), VLDL triglycerides (r = -.52), and apolipoprotein B (r = -.41). These relationships remained significant after adjustment for age, sex, body mass index, waist/hip ratio, fat cell volume, and circulating levels of insulin, noradrenaline, and adrenaline. beta-Receptor sensitivity accounted for 40% of the variance in total plasma triglycerides. beta-Receptor subtype sensitivity and binding capacity were also determined in fat cells using terbutaline (beta 2) and dobutamine (beta 1) bioassays and radioligand binding. Multiple regression analysis revealed that terbutaline sensitivity correlated inversely with total plasma triglycerides, apolipoprotein B, VLDL-C, and VLDL triglycerides (partial r from -.56 to -.42), but there was no correlation between dobutamine sensitivity and blood lipids (partial r from .05 to .18) or between receptor binding and blood lipids (partial r from .01 to .28). Thus, the lipolytic beta-receptor sensitivity in fat cells appears to play a hitherto-unrecognized role for lipoprotein metabolism, in particular that of VLDL. This relationship is receptor-subtype specific, particularly involving beta 2-receptors, and seems to be localized to a postreceptor step in lipolysis regulation. Low sensitivity may be of importance for the development of hypertriglyceridemia.

Adipose Tissue↗
PubMed1993

Tissue distribution of beta 3-adrenergic receptor mRNA in man.

Expression of mRNA for beta 1-, beta 2-, and beta 3-adrenergic receptors (beta 1-, beta 2-, and beta 3-AR) was investigated in human tissues. beta 1- and beta 2-AR mRNA distribution correlated with that of the cognate receptors established by pharmacological studies. beta 3-AR transcripts were abundant in infant perirenal brown adipose tissue, characterized by the presence of uncoupling protein (UCP) mRNA. In adult whole adipose tissues, beta 3-AR mRNA levels were high in deep deposits such as perirenal and omental, and lower in subcutaneous. In these deposits, UCP mRNA levels paralleled those of beta 3-AR. However, isolated omental and subcutaneous adipose cells, enriched in white adipocytes, expressed beta 3-AR but no UCP transcripts. beta 3-AR mRNA was highly expressed in gallbladder, and to a much lower extent in colon, independently of UCP mRNA. Quadriceps or abdominal muscles, heart, liver, lung, kidney, thyroid, and lymphocytes did not express intrinsic beta 3-AR mRNA. This study demonstrates that substantial amounts of brown adipocytes exist throughout life in adipose deposits, which are generally classified as white. These deposits are the main sites of beta 3-AR expression, which also occurs in gallbladder and colon. beta 3-AR may thus be involved in the control of lipid metabolism, possibly from fat assimilation in the digestive tract, to triglyceride storage and mobilization in adipose tissues.

Adipose Tissue↗
PubMed1993

Role of vascular alpha-2 adrenoceptors in regulating lipid mobilization from human adipose tissue.

The role of alpha-2 adrenoceptors in lipid mobilization and blood flow was investigated in situ using microdialysis of subcutaneous adipose tissue in nonobese healthy subjects. The alpha-2 agonist clonidine caused dose-dependent biphasic response with increased glycerol levels at low clonidine concentrations and decreased glycerol levels at concentrations > 10(-7) mol/liter. Similar results were observed with epinephrine plus propranolol. Clonidine action was unaffected in the presence of labetalol (beta-/alpha-1 antagonist) but completely blunted by the presence of yohimbine (alpha-2 antagonist). The pseudolipolytic effect of clonidine was significantly more pronounced in gluteal as compared with abdominal adipose tissue. When clonidine was added together with the vasodilating agents nitroprusside or hydralazine, the pseudolipolytic effect was abolished and a dose-dependent decrease in dialysate glycerol was observed at all clonidine concentrations (10(-10)-10(-4) mol/liter). When ethanol was added to the perfusate to monitor blood flow, the escape of alcohol from the dialysate was accelerated by 30% with hydralazine or nitroprusside (P < 0.01) and 30% retarded (P < 0.05) by clonidine (10(-10) mol/liter). Thus, the results demonstrate an important role of blood flow for regulating lipid mobilization from adipose tissue in vivo. Alpha-2 adrenoceptor activation causes marked retention of lipids in adipose tissue due to vasoconstriction in combination with antilipoiysis.

Adipose Tissue↗
PubMed1993

Adrenergic regulation of human adipose tissue metabolism in situ during mental stress.

The adrenergic regulation of adipose tissue lipolysis and glucose metabolism was investigated in situ during a standardized mental stress test in 11 nonobese, healthy subjects, using microdialysis of the extracellular water space in sc adipose tissue. Microdialysis probes were inserted in the abdominal sc fat, and were perfused using solvents with or without adrenoceptor blocking agents. The tissue dialysate concentrations of glycerol (lipolysis index) glucose, lactate, and pyruvate were determined. The glycerol concentration in adipose tissue increased markedly during the stress test and decreased in the poststress period. A similar kinetic pattern was observed in blood. In situ administration of the nonselective beta-adrenoceptor blocking agent propranolol almost completely prevented the stress-induced increase in adipose tissue glycerol levels, whereas a nonselective alpha-adrenoceptor blocking agent (phentolamine) was ineffective in this respect. Plasma levels of glucose and lactate remained unaltered during and after the stress test; at the same time plasma pyruvate decreased moderately. By contrast, glucose, lactate, and pyruvate in adipose tissue increased by 25-30% during or after the stress (P < 0.05). The increase in lactate and pyruvate in adipose tissue after the stress was completely off-set by alpha-adrenoceptor blockade in situ, whereas beta-adrenoceptor blockade in situ did not influence the kinetic pattern of these metabolites. It is concluded that the lipolytic activity in human adipose tissue is markedly enhanced during mental stress, owing to adrenergic mechanisms that are mediated via beta-adrenoceptors. After mental stress, adipose tissue glucose utilization is decreased and routed toward nonoxidative pathways. The latter seems to involve adrenergic effects that are mediated via alpha-adrenoceptors.

Adipose Tissue↗
PubMed1993

Expression of beta 1- and beta 2-receptor genes and correlation to lipolysis in human adipose tissue during childhood.

beta 1- and beta 2-adrenoceptor (bar1 and bar2) mRNA levels were measured in adipose tissue obtained from children (between 1 month and 10 yr of age) and adults during inguinal hernia operations. Bar1 mRNA levels were constant in all age groups studied. In infants and children less than 7 yr old, bar2 levels were twice as high (P < 0.01) as those in adults, and in infants 1-4 months old, bar2 mRNA levels were higher than bar1 levels (P < 0.01). The bar2/bar1 ratio gradually decreased, and in adults, there was 2.3-fold higher bar1 mRNA expression (P < 0.01). In infants 1-5 months old, the lipolytic sensitivity to noradrenaline was 5 times lower (P < 0.05) than that in adults, whereas the sensitivity to adrenaline and isoprenaline was unchanged. The maximal lipolytic response to adrenaline was higher than that to noradrenaline in infants (P < 0.01), whereas the opposite was found in adults (P < 0.01). The lipolytic sensitivity to the bar1-selective agonist dobutamine was not influenced by age, whereas the sensitivity to the bar2-selective agonist terbutaline was 10,000 times higher in infants than in adults. In conclusion, these data indicate subtype-specific developmental changes in bar expression, with higher bar2 mRNA levels accompanied by increased bar2-induced lipolysis during infancy.

Adipose Tissue↗
PubMed1993

Changes in circulating lipid and carbohydrate metabolites following systemic nicotine treatment in healthy men.

In the present study the influence of low doses of intravenous nicotine administration on hormonal and metabolic events was studied in man in view of the clinical implications of moderate smoking on the development of hyperlipidemia. Hormonal, metabolic and cardiovascular effects of a 30 min intravenous nicotine infusion (0.25 or 0.5 microgram/kg/min) were determined in seven non-smoking, healthy, normal weight male individuals after an overnight fast. Nicotine caused a significant dose-dependent increase in the plasma levels of nicotine, cotinine, noradrenaline, adrenaline, glycerol and free fatty acids (FFA). The serum nicotine concentrations peaked at the end of the infusion followed by a gradual decline, although they were still increased 90 min after cessation of infusion. Serum cotinine levels (the main nicotine metabolite) continuously increased during the experiment and statistically significant increases were found from 30 min after the start of infusion of nicotine. Serum noradrenaline, adrenaline, glycerol and FFA levels had increased significantly by 15 min of nicotine infusion. Nicotine produced significant elevations of adrenaline, glycerol and FFA concentrations at both doses (maximal increments of 247, 184 and 153%, respectively) and the peak effect occurred at 30 min. However, noradrenaline levels only responded to the high nicotine dose and the maximal increment (168%) was already found at 15 min. The increments of noradrenaline and adrenaline failed to elicit changes in systolic and diastolic blood pressure or heart rate. Nicotine did not alter plasma levels of glucagon, insulin, glucose, pyruvate or lactate and a non-significant increase in serum cortisol and growth hormone levels was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of phosphodiesterase inhibition with amrinone or theophylline on lipolysis and blood flow in human adipose tissue in vivo as measured with microdialysis.

Phosphodiesterase III (cyclic GMP-inhibited, particulate, low Km) is believed to play a dominant role in the cyclic AMP breakdown and lipolysis regulation in fat cells. Its importance for lipolysis activity was investigated in situ in humans by comparing the effects of a selective (amrinone) and a nonselective (theophylline) inhibitor of the enzyme. Abdominal subcutaneous adipose tissue of healthy nonobese humans was microdialyzed with solvents containing one or both of these agents, and glycerol (lipolysis index) or the escape of ethanol from the dialysis solvent (blood flow index) was continuously monitored in the perfusate. Both agents caused a dose-dependent and sustained increase in the glycerol level in the perfusate for at least 2.5 h. Although amrinone was 5000 times more potent than theophylline on a molar basis, its maximum activity was only 35% as compared to the maximum activity of theophylline. Half-maximum lipolytic effect of the two drugs occurred at about 0.1 mumol/l and 1 mmol/l, respectively (P < 0.001). At maximum effective concentrations, amrinone stimulated lipolysis by about 63% and theophylline by about 200% (P < 0.01). At these concentrations amrinone increased the rate of disappearance of ethanol from the perfusate by about 20% and theophylline increased the rate by about 75%, the difference being statistically significant (P < 0.01). When the two drugs were added together, the level of lipolysis stimulation was not different from that with theophylline alone both at maximal and submaximal effective concentrations of drug combinations.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Release of small amounts of free fatty acids from human adipocytes as determined by chemiluminescence.

A semiautomatic luminometric method for determination of small amounts of free fatty acids (FFA) released from human adipocytes in vitro is described. Bovine serum albumin (BSA) is used as acceptor of free fatty acids in the incubation medium of isolated fat cells. The assay involves pretreatment with the detergent sodium dodecyl sulfate (SDS) to liberate the free fatty acids from the bovine serum albumin before activation by acyl-CoA synthetase (ACS) (EC 6.2.1.3). This is followed by oxidation of the resulting thioesters by acyl-CoA oxidase (ACO). The H2O2 formed is subsequently measured in a horseradish peroxidase (HRP) (EC 1.11.1.7)-catalyzed luminol reaction. The assay is linear in the interval of 0.01-1 nmol in the cuvette corresponding to 2-200 microM in the sample, and 25 samples are automatically assayed in the luminometer within 75 min. FFA release could easily be studied in a small incubation volume (200 microliters) of very diluted (10(4) cells/ml) human adipocyte suspensions. Samples (25 microliters) containing 0.25% BSA from incubates of adipose tissue cells did not interfere with the standard curve. The analytical interference from different factors that could be used in studies of lipolysis was investigated. No interference was observed up to the following concentrations: 5 microM epinephrine, 5 microM norepinephrine, 80 microM isoproterenol, 1 mM insulin, 2.5 mM propranolol, 5 mM phentolamine, and 5 microM ascorbate. Results obtained with the present assay were highly correlated (r = 0.997) with those obtained by a 260-times less sensitive spectrophotometric kit method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

Effect of insulin on human adipose tissue metabolism in situ. Interactions with beta-adrenoceptors.

The effects of insulin, and its interactions with catecholamines through beta-adrenoceptors, on human adipose tissue glucose utilization and lipolysis were investigated in vivo. Microdialysis of the extracellular compartment of abdominal subcutaneous adipose tissue was performed in healthy subjects of normal weight, before and during a 2-h hyperinsulinaemic (61 +/- 3 mU/l), euglycaemic clamp. The tissue was perfused with or without the beta-adrenergic agonist isoproterenol (10(-6) mol/l), and the tissue dialysate concentrations of glucose, glycerol (lipolysis index) lactate and pyruvate were determined. During the insulin infusion, glucose in adipose tissue decreased by 20% (p less than 0.001), despite arterial steady-state normoglycaemia. The concentrations of lactate and pyruvate increased gradually to a steady-state plateau of twice the basal level in adipose tissue and arterial blood. Insulin-induced suppression of glycerol (lipolysis index) was, if anything, more marked in adipose tissue than in plasma (65% vs 50% decrease from baseline levels, p less than 0.05). In situ perfusion of adipose tissue with isoproterenol, starting either at the beginning of the study period or at 45 min after initiation of the insulin infusion, resulted in marked and rapid elevations of all the investigated metabolites in the adipose tissue extracellular compartment (p less than 0.05-0.005). It is concluded that insulin action on glucose uptake and lipolysis in human adipose tissue in vivo is counteracted by beta-adrenoceptor stimulation. In contrast, insulin and beta-adrenoceptors have synergistic effects on non-oxidative glucose metabolism in human adipose tissue in situ.

Adipose Tissue↗
PubMed1992

Microdialysis measurement of the absolute glucose concentration in subcutaneous adipose tissue allowing glucose monitoring in diabetic patients.

The possibility of continuously monitoring the absolute glucose concentration in subcutaneous adipose tissue, using microdialysis of the extracellular water space, was investigated in six Type 1 (insulin-dependent) diabetic patients. By using a large microdialysis probe (30 x 0.62 mm), and by perfusing with a low flow rate (0.5 microliters/min), complete recovery of glucose was attained in vitro. In the patients the dialysis probe was implanted subcutaneously, perfused by a wearable microinfusion pump, and dialysate samples were collected in 60-min fractions over 10 h. The absolute glucose concentration in the tissue dialysate was the same or almost the same as the blood glucose concentration (range 87-101% of the blood glucose value). The changes in blood glucose were closely paralleled by the variations in adipose tissue glucose (r = 0.93, p < 0.01), and the recovery of glucose in the microdialysate remained constant during the 10-h study period. In conclusion, it is possible, using microdialysis, to directly determine the absolute glucose concentration in subcutaneous adipose tissue. Hence, this technique may be used for continuous glucose monitoring in diabetic patients.

Adipose Tissue↗
PubMed1992

Effects of mental stress on lipolysis in humans.

Lipid mobilization was investigated in subcutaneous adipose tissue specimens obtained before and after a standardized mental-stress test in 14 non-obese healthy subjects. All participants responded with an increased heart rate and elevation of plasma glycerol levels. Plasma norepinephrine concentrations remained unchanged throughout the test. In six subjects, mental stress induced a significant increase in plasma epinephrine levels, to more than 0.26 nmol/L (responders), while the remaining eight individuals showed a response of less than 0.12 nmol/L (nonresponders). In the responders, a 30% increase in catecholamine-stimulated in vitro lipolysis was found after the mental-stress test, while the lipolytic response in isolated fat cells in vitro decreased slightly in the nonresponders after mental stress. A strong correlation (r = .84) was observed between the increased in vitro lipolytic responsiveness due to mental stress and circulating plasma epinephrine levels. In vitro data suggest that the augmentation in lipolytic activity induced by acute mental stress was caused by alterations between the beta-adrenoceptor and adenylate cyclase, ie, probably an increased coupling between beta-receptors and the stimulatory guanosine triphosphate [GTP]-binding protein (G2). This, in combination with elevated levels of circulating epinephrine, may explain the increased lipolysis during mental stress in some individuals (ie, responders). However, other parallel mechanisms for activation of lipolysis during mental stress must also exist in certain individuals (ie, nonresponders), and seem not to involve the adrenergic system.

Adipose Tissue↗
PubMed1992

Adrenergic receptor function in fat cells.

All classical adrenoceptor subtypes are functionally expressed in fat cells. However, only beta 1 adrenoceptors appear to be present in all types of fat cells. There is a substantial adrenoceptor reserve in fat cells; approximately 50% of beta and alpha 2 adrenoceptors are spare receptors. Beta adrenoceptors are subject to intensive regulation. They are regulated by insulin, estrogens, and androgens as well as by thyroid hormones and are altered by nutritional factors, diabetes, autonomic neuropathy, and beta-blocking treatment. Alpha receptors are less sensitive to changes except during infancy, when there are marked developmental alterations in the function of alpha 2 adrenoceptors, and during fasting, when there is a decrease in receptor expression. In addition, beta adrenoceptors but not alpha 2 adrenoceptors are sensitive to homologous desensitization after exposure to agonists. Site variations in the expression and function of beta and alpha 2 adrenoceptors, which in part are situated at the level of gene transcription, may be involved in the development of regional obesity.

Adipose Tissue↗
PubMed1992

Importance of beta-adrenoceptor function in fat cells for lipid mobilization.

The role of peripheral catecholamine sensitivity in lipid mobilization was investigated in 78 healthy non-obese subjects by comparing beta-adrenergic regulation of lipolysis in isolated adipocytes with circulating catecholamines and glycerol (lipolysis index). Small intra-individual variations (5-7%) in adipocyte lipolytic beta-adrenoceptor sensitivity (ED50) for isoprenaline were found. However, large inter-individual variations (almost 10(5)-fold) in isoprenaline ED50 were observed in abdominal or gluteal adipocytes, which correlated (r = 0.52) negatively with the resting plasma noradrenaline levels. A correlation was also observed between circulating noradrenaline and adipocyte ED50 for noradrenaline (r = -0.38). In subjects with high (ED50 less than 10(-11) mol l-1) as compared to low isoprenaline sensitivity (ED50 greater than 10(-10) mol l-1) physical exercise induced a two times greater increase in plasma glycerol (P less than 0.01), in spite of a 50% less marked increase of plasma noradrenaline (P less than 0.01). Findings with beta-adrenoceptor mRNA and with total beta-adrenoceptor number or affinity for agonist did not show any strong correlation with the resting plasma noradrenaline level (r less than 0.25). In conclusion, inter-individual variations in beta-adrenoceptor sensitivity and its relation to circulating noradrenaline can be ascribed to specific modulations of either BAR-subtypes or in the postreceptor activation of lipolysis. These variations in adipocyte beta-adrenoceptor sensitivity may participate in the regulation of peripheral nervous activity and play a putative role in lipolysis during exercise when subjects with high beta-adrenoceptor sensitivity increased their ability to mobilize lipids despite a reduced noradrenaline response.

Adipose Tissue↗
PubMed1992

Lipolytic catecholamine resistance due to decreased beta 2-adrenoceptor expression in fat cells.

The existence of lipolytic beta-adrenoceptor (BAR) resistance was investigated in vivo and in isolated abdominal subcutaneous adipocytes in 65 healthy and drug-free subjects. The concentration of isoprenaline (nonselective BAR agonist) causing half-maximum lipolysis effect (ED50) varied bimodally and 10(6)-fold between individuals but was almost constant in the same subject when measured two times at rest or before and 30 min after exercise. The subjects were categorized as having either high or low isoprenaline sensitivity. The former group had a 50% reduced in vivo lipolytic response to exercise and mental stress, despite a 50% increased plasma noradrenaline response (P < 0.01) and a 350% increased plasma adrenaline response (P < 0.02). In fat cells the lipolytic ED50 values for noradrenaline and terbutaline (BAR2 agonist) were 10 times lower (P < 0.001) in low-sensitive subjects, but the maximum lipolytic actions of these agents (and of isoprenaline) were similar in both groups. The action on lipolysis of dobutamine (BAR1 agonist), forskolin (stimulating adenylate cyclase), dibutyryl cyclic AMP (activating protein kinase), clonidine (alpha 2-adrenergic agonist), or phenyl isopropyladenosine (adenosine receptor agonist) were almost identical in high- and low-sensitivity subjects. ED50 for isoprenaline correlated with ED50 for terbutaline (r = 0.75), but not with ED50 for dobutamine. In high-sensitivity subjects the number of BAR2 was almost three-fold increased (P < 0.002) and the steady-state adipocyte mRNA level for BAR2 was sixfold increased (P < 0.005). BAR2 affinity as well as BAR1 number, affinity and mRNA expression were similar in both groups. In 11 cholecystectomy patients (otherwise healthy) lipolytic ED50 for beta agonists correlated in omental and subcutaneous fat cells (r = 0.85 for isoprenaline; r = 0.95 for terbutaline). In conclusion, lipolytic resistance to catecholamines is present in vivo in apparently healthy subjects due to reduced expression of BAR2 in adipocytes.

Adipose Tissue↗