Changes in cerebrospinal fluid signalling substances and appetite scores following 48 h fast in healthy volunteers.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
P Arner
Publications and source records attributed to P Arner.
Effects of glucocorticoids on leptin levels and eating behaviour in women.
OBJECTIVE: Long-term treatment with glucocorticoids induces weight gain and increased risk to develop obesity-related metabolic complications. The underlying mechanisms are not fully understood. Glucocorticoid therapy has previously been associated with increased levels of circulating leptin. In this study the eating behaviour was therefore studied in relation to leptin levels before and after short-term prednisolone treatment. DESIGN: Within-subject design. SUBJECTS: Twelve healthy postmenopausal women with a mean body mass index (BMI) of 28.9 kg m-2 (+/-0.8 SEM) volunteered after recruitment by an advertisement in the local paper. INTERVENTIONS: The subjects received 25 mg prednisolone daily for 7 days. MAIN OUTCOME MEASUREMENTS: Fasting serum samples were obtained before, during and after treatment for determination of leptin and insulin, glucose and fractionated lipoproteins in plasma. The microstructure of the eating behaviour was registered with a universal eating monitor, VIKTOR. Appetite was estimated by visual analogue rating scales and food intake by a 48-h recall. RESULTS: Serum leptin increased after 2 and 7 days of glucocorticoid administration (P < 0.01), and the food intake measured by VIKTOR after 7 days of treatment (P < 0.05). No statistically significant changes were however, found in the 48-h food- recall or in the subjective appetite registrations. Insulin levels were borderline elevated (P = 0.062) after treatment, but no significant changes of fasting glucose were seen. High density lipoprotein cholesterol (HDL) increased (P < 0.05), whilst low density lipoprotein cholesterol (LDL) decreased (P < 0.05). CONCLUSION: Food intake was elevated after glucocorticoid administration as observed with an objective, quantitative method, in spite of increased levels of circulating leptin.
Body Mass Index↗
Absence of functional insulin receptor substrate-3 (IRS-3) gene in humans.
AIM/HYPOTHESIS: Insulin receptor substrate (IRS) proteins play important roles in insulin action and pancreatic beta-cell function. At least four mammalian IRS molecules have been identified. Although genes and cDNAs encoding human IRS-1, IRS-2, and IRS-4 have been cloned, IRS-3 has been identified only in rodents. Thus, we have attempted to clone the human IRS-3 gene. METHODS: Insulin-stimulated rat or human adipocytes were subjected to Western blot analysis to assess IRS-3 tyrosine phosphorylation. Human liver and adipose cDNA libraries were screened in an effort to clone IRS-3 cDNA. A PCR-based approach was designed to amplify IRS-3 cDNA. Reverse transcription PCR was carried out using mRNA from adipose tissue, liver, and skeletal muscle as templates in combination with an in silico screen using mouse IRS-1, IRS-2 and IRS-3 in a tblastn search of the draft public human genome. RESULTS: In human adipocytes we did not detect a M(r) 60 000 phosphoprotein corresponding to IRS-3, whereas in rat adipocytes IRS-3 protein and insulin-stimulated tyrosine phosphorylation was readily observed. None of the molecular approaches provided evidence for a functional IRS-3gene in human tissue. Two deletions in human IRS-3 gene were identified using bioinformatics. The human IRS-3 gene product is predicted to lack a phosphotyrosine binding domain and also the sequence corresponding amino acid 353-407 of murine IRS-3. The contiguous sequence of genomic DNA between these two homologous regions does not have the coding information for human IRS-3. CONCLUSION/INTERPRETATION: In silico screening of the human IRS-3 genome region, combined with further biological and molecular validation, provides evidence against a functional IRS-3 in humans.
Adipocytes↗
Insulin signal transduction and glucose transport in human adipocytes: effects of obesity and low calorie diet.
AIM/HYPOTHESIS: We examined insulin signal transduction at the level of insulin receptor substrates (IRS) 1 and 2, phosphatidylinositol (PI) 3-kinase and glucose transport in isolated subcutaneous adipocytes from obese and lean women. METHODS: Glucose transport and insulin signalling were investigated in isolated adipocytes from six obese women (BMI 36-43 kg/m(2)) (before and after 11 days of very low calorie diet) and from six lean women (BMI 22-26 kg/m(2)). RESULTS: Insulin sensitivity of glucose transport was reduced in adipocytes from obese women (p<0.05), with further reductions in basal and maximal insulin-stimulated glucose transport after a very low calorie diet (p<0.05). In obese women, IRS-1 associated PI 3-kinase activity was markedly impaired (p<0.05), whereas, IRS-2 associated PI 3-kinase activity was normal. IRS-1 associated PI 3-kinase activity remained blunted after a very low calorie diet, whereas IRS-2 associated PI 3-kinase activity was increased. GLUT4 protein was reduced by 37% in obese versus lean subjects (p<0.05), and decreased further after a very low calorie diet (from 19+/-4 to 14+/-4 arbitrary units; p<0.05). CONCLUSION/INTERPRETATION: IRS-1 signalling to PI 3-kinase is a site of insulin resistance in adipocytes from obese women, whereas insulin action on IRS-2 is normal. Thus, IRS-1 and IRS-2 undergo differential regulation in adipocytes from obese insulin resistant subjects. Finally, a very low calorie diet is associated with a further impairment in glucose transport in adipose tissue. The defect in glucose transport after a very low calorie diet occurs independent of further defects in insulin signalling at the level of the PI 3-kinase.
Adipocytes↗
Polymorphism in the Calpain 10 gene influences glucose metabolism in human fat cells.
AIMS/HYPOTHESIS: A common G to A polymorphism ( UCSNP-43) in the Calpain 10 gene was recently found to be associated with Type II (non-insulin-dependent) diabetes mellitus and variations in post-absorptive and insulin stimulated glucose metabolism in vivo. We aimed to study the influence of Calpain 10 polymorphism on insulin action in fat cells. METHODS: Calpain 10 polymorphism ( UCSNP-19, -43 or -63) were set in relation to lipolysis and lipogenesis in isolated subcutaneous adipocytes of 46 apparently healthy non-obese subjects. RESULTS: For UCSNP-43 the G/G genotype had twofold higher basal and insulin stimulated rates as compared with AA/AG genotypes. However, there was no genotype effect on basal or insulin inhibited lipolysis rates in fat cells. The protein amount of GLUT 4 in adipocytes was not influenced by the polymorphism. Fat cells expressed mRNA for the Calpain 10 gene at a relatively high concentration, about 4 amol/microg RNA, which is similar to that of uncoupling protein-2. Neither a UCSNP-19 nor a UCSNP-63 polymorphism in the Calpain 10 gene was found to be associated with basal or insulin-induced adipocyte lipolysis and lipogenesis. None of the polymorphisms influenced body mass index or fasting plasma concentrations of insulin and glucose in 693 non-obese healthy subjects. CONCLUSIONS/INTERPRETATION: The Calpain 10 gene could be involved in the regulation of glucose metabolism but not lipolysis in human fat cells, although it does not involve adipocyte GLUT-4 protein content. It is possible that the Calpain 10 gene predisposes to diabetes by influencing the glucose metabolism.
Adenine↗
The common -675 4G/5G polymorphism in the plasminogen activator inhibitor -1 gene is strongly associated with obesity.
AIMS/HYPOTHESIS: Plasminogen activator inhibitor 1 (PAI-1) increases in several insulin-resistant conditions such as obesity. We tested the hypothesis that the PAI-1 gene might be a candidate for obesity and Type II (non-insulin-dependent) diabetes mellitus. METHODS: We investigated the frequency of a common and functional -675 4G/5G promoter polymorphism in the PAI-1 gene in 188 lean, 70 overweight (BMI 25-30 kg/m(2)) and 247 obese otherwise healthy Scandinavian subjects. RESULTS: The genotypic ( p = 0.002), or allelic ( p = 0.0004) distribution differed markedly between the three groups. Homozygosity for 4G was more common among obese people, whereas homozygosity for 5G was more common among lean subjects. Heterozygosity was evenly distributed. The lean and overweight groups did not differ in frequency distribution. The relative risk for being obese in comparison to being lean for 4G/4G was threefold higher ( p = 0.0003). Also, carriers of the 4G allele in the heterozygous or homozygous form were distributed differently between the three groups ( p = 0.006). The 4G carriers were more common among the obese than the lean group. The latter group did not differ from the overweight group. The relative risk of being obese in comparison with lean was twofold increased in 4G carriers ( p = 0.0015). Similar results were obtained in men and women. CONCLUSION/INTERPRETATION: Thus, the common -675 4G/5G polymorphism in the PAI-1 gene is strongly linked to obesity and a markedly increased risk for obesity is associated with the 4G allele in its homozygous form.
Adult↗
A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding.
AIM: To determine whether visceral fat reduction in connection with bariatric surgery could improve weight loss and metabolic profile of obese subjects. PATIENTS AND METHODS: In a one-center, randomized and controlled pilot trial we assigned 50 subjects with severe obesity (body mass index >35 kg/m(2)) to either adjustable gastric banding (AGB) alone (11 men and 14 women), or AGB plus surgical removal of the total greater omentum (11 men and 14 women). The patients were followed at regular intervals for 2 y and examined at 0 and 24 months with respect to body composition and metabolic profile. RESULTS: No significant differences between control and omentectomized patients were observed at baseline. The removed greater omentum constituted 0.8+/-0.4% (mean+/-s.d.) of total body fat. At 2 y follow-up there was an expected decrease in body weight and an improvement in metabolic profile in both groups. Although omentectomized subjects tended to lose more weight than control subjects the difference was not statistically significant and changes in waist-to-hip ratio and saggital diameter did not differ between groups. However, the improvements in oral glucose tolerance, insulin sensitivity and fasting plasma glucose and insulin were 2-3 times greater in omentectomized as compared to control subjects (P from 0.009 to 0.04), which was statistically independent of the loss in body mass index. No differences in blood lipids between the groups were recorded. No adverse effects related to omentectomy were observed. CONCLUSIONS: Omentectomy, when performed together with AGB, has significant positive and long-term effects on the glucose and insulin metabolic profiles in obese subjects.
Adult↗
A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin.
There is a large inter-individual variation in circulating leptin concentrations at each level of body fat content. The reason for this is unknown. We investigated whether a polymorphism in the promoter region of the leptin gene (-2548G/A) influences gene transcription and leptin expression in 39 non-obese female subjects. Eleven subjects were homozygous for the AA genotype, 18 were heterozygous (GA) and 10 carried the GG genotype. AA subjects had higher levels of serum leptin than did GA/GG subjects (14.5 +/- 2.1 vs. 9.7 +/- 0.9 ng/ml, p = 0.02). Adipose tissue leptin secretion rate in AA subjects was twice as high as in GA/GG subjects: 1158 +/- 288 vs. 626 +/- 84 ng/2 h/10 (7) cells (p = 0.02). These differences were also statistically significant with leptin levels adjusted for body mass index (p = 0.03 - 0.04). Adipose tissue leptin mRNA levels were 60 % higher in AA subjects, as compared to GA/GG subjects, 74 +/- 10 vs. 46 +/- 4 amol/ micro g RNA (p = 0.01). EMSA revealed that nuclear extracts derived from both U937 cells and human adipocytes form a protein-DNA complex with the leptin -2548G/A polymorphic site and bind with higher affinity to the -2548A-site. In conclusion, a common polymorphism in the promoter of the human leptin gene (-2548G/A) influences leptin expression, possibly at the transcriptional level, and therefore also adipose secretion levels of the hormone.
Adipose Tissue↗
Secretion of free and protein-bound leptin from subcutaneous adipose tissue of lean and obese women.
Leptin circulates as a free (FL) and a protein-bound (BL) form, with the soluble leptin receptor (LR) as an important binding compound. Here we measured these components of leptin in serum and in the incubation medium of sc adipose tissue in healthy lean (n = 10) and obese (n = 13) female subjects using recently developed specific RIA systems. In addition, immunostaining for FL, BL, and LR in adipose tissue was performed. Serum FL levels were increased in the obese subjects (P < 0.0001), whereas BL and LR concentrations in serum of lean and obese subjects were similar. Both FL and BL were secreted from human preadipocytes and increased in parallel to the differentiation of the cells. In sc fat cell explants LR antibodies predominantly stained the fat cell membrane, whereas FL and BL antibodies revealed intracytoplasmatic adipocyte staining. The release of FL, BL, and LR from adipose tissue was increased in obese compared with lean subjects (P < 0.005 for FL; P < 0.02 for BL, and P < 0.01 for LR). In summary, fat cells are capable of releasing not only FL, but also BL and LR.
Adipocytes↗
In vivo physiological changes in the synovial membrane of the knee during reperfusion after arthroscopy. A study using the microdialysis technique.
We have used in vivo microdialysis to monitor postoperative physiological events in the synovial membrane after arthroscopy. The levels of lactate were significantly higher in the synovial membrane than in the reference tissue (subcutaneous fat) and there was a significant increase in lactate after operation. Blood flow, measured as the ethanol ratio, was stable in both tissues. Our findings show that there was an increase in the local production of lactate since the levels of lactate in blood and the reference tissue were comparable and did not show a significant increase. There was also a consumption of glucose in the synovial membrane which was not observed in the reference tissue. The levels of pyruvate were higher in the synovial membrane. A state of reperfusion occurs in the synovial membrane after moderate trauma such as standard arthroscopy of the knee. Microdialysis should be further evaluated in studies of the in vivo physiology of the synovial membrane.
Adipose Tissue↗
Fatty acid binding protein expression in different human adipose tissue depots in relation to rates of lipolysis and insulin concentration in obese individuals.
Two fatty acid binding proteins (FABPs) are expressed in adipose tissue, adipocyte lipid binding protein (ALBP) and keratinocyte lipid binding protein (KLBP). This study investigated FABP expression in visceral and subcutaneous human adipose tissue depots and associations with lipolytic differences between the depots and circulating insulin concentrations. ALBP and KLBP (protein and RNA) were quantified in subcutaneous and omental adipose tissue from obese individuals and expressed relative to actin. ALBP RNA and protein expression was significantly higher in subcutaneous compared to omental adipose tissue (both p < 0.05), whereas KLBP RNA and protein expression was no different between the two sites. There were significant inverse correlations between serum insulin concentrations and the ALBP/KLBP RNA ratio in both subcutaneous and omental adipose tissue (both p < 0.02). Basal rates of glycerol and fatty acid release measured in adipocytes isolated from subcutaneous and omental adipose tissue were significantly higher in the former (p < or = 0.02). Therefore the relative ALBP/KLBP content of human adipose tissue is different in different adipose tissue depots and at the RNA level is related to the circulating insulin concentration, at least in obese subjects. The higher rates of basal lipolysis in adipocytes isolated from subcutaneous compared to omental adipose tissue might be related to the increased ALBP content of the former. Therefore adipose tissue FABPs are interesting candidates for investigation to further our understanding of the insulin resistance syndrome and regulation of lipolysis.
Actins↗
[Effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes].
INTRODUCTION: Microalbuminuria and hypertension are risk factors for the development of diabetic nephropathy. Blockade of the renin-angiotensin system reduces progression to diabetic nephropathy in type 1 diabetic patients, whereas similar data are lacking for hypertensive type 2 diabetic subjects. We evaluated the renoprotective effect of an angiotensin II receptor antagonist, irbesartan, in hypertensive type 2 diabetic patients with microalbuminuria. MATERIAL AND METHODS: Five hundred and ninety hypertensive type 2 diabetic patients with microalbuminuria were enrolled in this multinational, randomised, double-blind, placebo-controlled study of irbesartan 150 mg/daily or 300 mg/daily or matching placebo for two years. The primary outcome was time to progression to diabetic nephropathy, defined as a persistent overnight albuminuria > 200 micrograms/min and at least a 30 per cent increase from baseline. RESULTS: Baseline characteristics in the three groups were similar. Ten patients (5.2 per cent) receiving irbesartan 300 mg and 19 patients (9.7 per cent) receiving irbesartan 150 mg daily reached the primary end point, as compared to 30 (14.9 per cent) patients on placebo (hazard ratio 0.30 [95 per cent confidence interval 0.14 to 0.61], p < 0.001 and 0.61 [95 per cent confidence interval 0.34 to 1.08] p = 0.08), respectively). The average blood pressure throughout the study was 144/83, 143/83, and 141/81 mmHg in the placebo, irbesartan 150 mg and 300 mg group, respectively (p = 0.004 for systolic blood pressure). Serious adverse events were less frequent in the patients treated with irbesartan (p = 0.02). DISCUSSIONS: Irbesartan is renoprotective independently of its blood pressure lowering effect in type 2 diabetic subjects with microalbuminuria. It is safe and well tolerated.
Adult↗
The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.
BACKGROUND: Microalbuminuria and hypertension are risk factors for diabetic nephropathy. Blockade of the renin-angiotensin system slows the progression to diabetic nephropathy in patients with type 1 diabetes, but similar data are lacking for hypertensive patients with type 2 diabetes. We evaluated the renoprotective effect of the angiotensin-II-receptor antagonist irbesartan in hypertensive patients with type 2 diabetes and microalbuminuria. METHODS: A total of 590 hypertensive patients with type 2 diabetes and microalbuminuria were enrolled in this multinational, randomized, double-blind, placebo-controlled study of irbesartan, at a dose of either 150 mg daily or 300 mg daily, and were followed for two years. The primary outcome was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was greater than 200 microg per minute and at least 30 percent higher than the base-line level. RESULTS: The base-line characteristics in the three groups were similar. Ten of the 194 patients in the 300-mg group (5.2 percent) and 19 of the 195 patients in the 150-mg group (9.7 percent) reached the primary end point, as compared with 30 of the 201 patients in the placebo group (14.9 percent) (hazard ratios, 0.30 [95 percent confidence interval, 0.14 to 0.61; P< 0.001] and 0.61 [95 percent confidence interval, 0.34 to 1.08; P=0.081 for the two irbesartan groups, respectively). The average blood pressure during the course of the study was 144/83 mm Hg in the placebo group, 143/83 mm Hg in the 150-mg group, and 141/83 mm Hg in the 300-mg group (P=0.004 for the comparison of systolic blood pressure between the placebo group and the combined irbesartan groups). Serious adverse events were less frequent among the patients treated with irbesartan (P=0.02). CONCLUSIONS: Irbesartan is renoprotective independently of its blood-pressure-lowering effect in patients with type 2 diabetes and microalbuminuria.
Adult↗
Fatty acid binding protein expression in different adipose tissue depots from lean and obese individuals.
AIMS/HYPOTHESIS: This study investigated the expression of adipose tissue fatty acid binding proteins (FABPs) in subcutaneous and visceral human adipose tissue depots from lean and obese individuals. METHODS: Adipocyte lipid binding protein (ALBP) and keratinocyte lipid binding protein (KLBP) expression was quantified by western blot in subcutaneous and omental adipose tissue from 20 obese and 9 lean individuals. RNA expression was quantified by Northern blot in the obese subjects. RESULTS: In the obese subjects, ALBP protein and RNA expression was higher in subcutaneous compared with omental adipose tissue (increases of 31 +/- 14 % and 40 +/- 13 % respectively, both p < 0.05), whereas in the lean group, KLBP protein levels were 32 +/- 9 % lower in subcutaneous fat (p < 0.03). However, the ALBP/KLBP ratio was greater in subcutaneous compared to omental adipose tissue from both lean and obese subjects: increases of 187 +/- 71 % (p = 0.01) and 52 +/- 23 % (p = 0.17) respectively for the protein ratio, and 21 +/- 6 % for RNA (p = 0.01, obese individuals). In lean subjects, insulin concentrations correlated positively with the ALBP/KLBP protein ratio in both depots (both p < or = 0.03). CONCLUSION/INTERPRETATION: There are regional differences in adipose tissue FABP expression, which could be influenced by obesity. However, the ALBP/KLBP ratio is greater in subcutaneous than visceral adipose tissue in lean as well as in obese subjects. Investigation of adipose tissue FABPs could further our understanding of the role of fatty acids in the insulin resistance syndrome.
Actins↗
The effect of the beta(2) adrenoceptor gene Thr164Ile polymorphism on human adipose tissue lipolytic function.
A rare beta(2)-adrenoceptor gene polymorphism, Thr164Ile, has been described that impairs receptor function when transfected into cell lines. We investigated whether the polymorphism influences native receptor function by studying lipolysis in freshly isolated subcutaneous fat cells from 236 apparently healthy subjects. Twelve subjects were heterozygous for the 164Ile variant. The fat cells of Ile carriers displayed a 6 fold increase (P=0.02) in the lipolytic EC(50) of terbutaline (a selective beta(2)-adrenoceptor agonist), but no change in the lipolytic action of dobutamine (a selective beta(1)-adrenoceptor agonist), compared with the Thr carriers. Maximum adrenoceptor agonist stimulated lipolysis did not differ between Thr and Ile carriers. The influence of two other polymorphisms (Arg16Gly and Gln27Glu) in the beta(2)-adrenoceptor gene was considered. Six 164Ile carriers also carried the 16Gly and 27Glu alleles. The latter combination occurred among 105 of the 164Thr carriers. For the 16Gly27Glu subgroup, the EC(50) of terbutaline was about 10 fold higher in 164Ile as than in 164Thr carriers (P=0.02) but there was no difference between genotypes in maximum terbutaline action. There was no difference between groups in dobutamine action. In conclusion, the 164Ile variant of the beta(2)-adrenoceptor is associated with a decreased native adipocyte receptor function, as evidenced by a marked increase in the half maximal effective concentration of the lipolytic action of a selective beta(2)-adrenoceptor agonist. This suggests that genetic variance in the beta(2)-adrenoceptor gene might be important for catecholamine function in humans, at least as far as adipocyte lipolysis is concerned.
Adipose Tissue↗
Systemic nicotine stimulates human adipose tissue lipolysis through local cholinergic and catecholaminergic receptors.
OBJECTIVE: To evaluate whether the lipolytic effects of systemic nicotine are not only attributed to indirect adrenergic mechanisms, but also to a direct action of nicotine on fat cells. DESIGN: The effect of a systemic nicotine infusion (0.5 microg/kg/min for 30 min) on lipolysis in subcutaneous adipose tissue was investigated in situ in 11 non-obese, non-smoking, healthy male subjects under placebo-controlled conditions. MEASUREMENTS: By using microdialysis probes the glycerol levels (lipolysis index) and blood flow were monitored locally in subcutaneous adipose tissue. RESULTS: Plasma nicotine levels peaked (7.2 ng/ml) at the end of the infusion. Nicotine induced a mean (+/-s.e.) percentage peak increase in adrenaline and noradrenaline plasma levels of 213+/-30% (P<0.01) and 118+/-5% (P<0.05), respectively. Nicotine increased venous plasma glycerol levels by 144+/-9% (P<0.001), arterialized plasma glycerol levels by 148+/-12% (P<0.001) and adipose glycerol levels by 148+/-16% (P<0.001), but did not alter blood flow. By inducing a local cholinoceptor blockade with mecamylamine (10(-5) M) via the microdialysis system, the increase in adipose glycerol levels was inhibited by approximately 45% (P=0.02). A corresponding local beta-adrenoceptor blockade with propranolol (10(-4) M), inhibited the increase in adipose glycerol levels by approximately 60% (P=0.02). Infusion of saline (ie placebo) had no effect on the parameters mentioned above. CONCLUSION: Systemically administered nicotine induces lipolysis, in part by activating the classical adrenergic mechanism (mediated by a nicotine-induced release of catecholamines stimulating beta-adrenoceptors), and in part by directly activating a nicotinic cholinergic lipolytic receptor located in adipose tissue.
Adipose Tissue↗
The Arg 389 Gly beta1-adrenergic receptor gene polymorphism and human fat cell lipolysis.
BACKGROUND: The beta1-adrenoceptor is a candidate gene for obesity because of its role in catecholamine-induced energy homeostasis. A common Arg 389 Gly variant polymorphism has been shown in recombinant cells to influence its-coupling properties. OBJECTIVE: To investigate the effect of the Arg 389 Gly beta1-adrenoceptor polymorphism on catecholamine-induced lipolysis in native human fat cells obtained by subcutaneous biopsy. SUBJECTS: Two-hundred and ninety-eight apparently healthy male and female subjects with a wide variation in body mass index (BMI, 18-60 kg/m2). MEASURES: The lipolytic sensitivities and maximum lipolytic action of noradrenaline and the selective adrenoceptor agonists dobutamine (beta1), terbutaline (beta2) and CGP 12177 (beta3) were determined in isolated subcutaneous adipocytes and related to beta-adrenoceptor radioligand binding parameters. RESULTS: No differences in the sensitivity or maximum lipolytic capacity of the agonists were found between the genotypes. This was true both when all subjects were analyzed together and when subgroups (lean, obese, men, women) were analyzed separately. Radioligand binding to beta1- or beta2-adrenoceptors was also similar between genotypes. The polymorphism had no important influence on either BMI or the distribution of obese and non-obese subjects between the genotypes. CONCLUSION: The distribution of the Arg 389 Gly polymorphism is similar in lean and obese subjects and has no apparent effect on the lipolytic response to beta-adrenergic stimulation in native human adipocytes. This suggests, despite the altered coupling properties reported in recombinant cells, that the Arg 386 Gly polymorphism has no important influence on human obesity.
Adipocytes↗
Regional differences in protein production by human adipose tissue.
Human adipose tissue has an important protein secretory function. Cytokines, hormones, prohormones and enzymes are secreted from fat cells and act in an endocrine or paracrine fashion. The production of several of these proteins is affected by obesity; normally there is an increase in the obese state. Protein production is, as a metabolic activity, subject to regional variations. In particular, the production of leptin, angiotensinogen, interleukin-6 and plasmin activator inhibitor-1 differs between subcutaneous and visceral adipose tissue sites, but no regional differences have been reported in the production of tumour necrosis factor alpha. It is possible that regional variations in protein production by adipose tissue are of importance in some of the endocrine and metabolic disturbances seen in various forms of obesity, such as visceral and upper-body obesity.
Adipose Tissue↗