Search PubMed⌕ Search

Biomedical subjects

D Langin

Publications and source records attributed to D Langin.

At least 73 records · Page 4Linked to original sources
PubMed1997

Lipolytic effects of conventional beta 3-adrenoceptor agonists and of CGP 12,177 in rat and human fat cells: preliminary pharmacological evidence for a putative beta 4-adrenoceptor.

1. The nature of rat and human fat cell beta 3-adrenoceptors was investigated by studying the effects of the new beta 3-adrenoceptor selective antagonist, SR 59,230A, on lipolysis induced by the conventional beta 3-adrenoceptor agonists, CL 316,243 and SR 58,611A, and by the non-conventional partial beta 3-adrenoceptor agonist CGP 12,177 (a potent beta 1- and beta 2-adrenoceptor antagonist with partial beta 3-adrenoceptor agonist property). 2. In rat fat cells, the rank order of potency of agonists was: CL 316,243 > isoprenaline > SR 58,611A > CGP 12,177. The three former agents were full agonists whereas CGP 12,177 was a partial agonist (intrinsic activity of 0.70). In human fat cells, the lipolytic effect of CGP 12,177 reached 25% of isoprenaline effect. CL 316,243 was a poor inducer of lipolysis and SR 58,611A was ineffective. 3. In rat fat cells, lipolysis induced by CL 316,243 and SR 58,611A was competitively antagonized by SR 59,230A. Schild plots were linear with pA2 value of 6.89 and 6.37, respectively. Conversely, 0.1, 0.5 and 1 microM SR 59,230A did not modify the concentration-response curve of CGP 12,177. A rightward shift of the curve was however observed with 10 and 100 microM of SR 59,230A. The apparent pA2 value was 5.65. The non-selective beta-adrenergic antagonist, bupranolol, competitively displaced the concentration-response curve of CGP 12,177 and CL 316,243. Schild plots were linear with pA2 values of 6.70 and 7.59, respectively. CL316,243-mediated lipolytic effect was not antagonized by CGP 20,712A. In human fat cells, CGP 12,177-mediated lipolytic effect was antagonized by bupranolol and CGP 20,712A. SR 59,230A (0.1, 1 and 10 microM) did not modify the concentration-response curve of CGP 12,177. A rightward shift was however observed at 100 microM leading to an apparent pA2 value of 4.32. 4. The results suggest that the non-conventional partial agonist CGP 12,177 can activate lipolysis in fat cells through the interaction with a beta-adrenoceptor pharmacologically distinct from the beta 3-adrenoceptor, i.e. through a putative beta 4-adrenoceptor. They suggest that the two subtypes coexist in rat fat cells whereas only the putative beta 4-adrenoceptor mediates lipolytic effect of CGP12,177 in human fat cells.

Adipocytes↗
PubMed1997

Adrenergic regulation of adipocyte metabolism.

Five adrenoceptor (AR) subtypes (beta 1, beta 2, beta 3, alpha 2 and alpha 1), are involved in the control of white and brown fat cell function. A number of metabolic events are controlled by the adrenergic system in fat cells. The stimulatory effect of catecholamines on lipolysis and metabolism is mainly connected to increments in cAMP levels, cAMP protein kinase activation and phosphorylation of various target proteins. Norepinephrine and epinephrine operate through differential recruitment of alpha 2- and beta-AR subtypes on the basis of their relative affinity for the different subtypes (the relative order of affinity is alpha 2 > beta 1 > or = beta 2 > beta 3 for norepinephrine). Antagonistic actions at the level of cAMP production exist between alpha 2- and beta 1-, beta 2- and beta 3-AR-mediated lipolytic effects in human white fat cells. The role of fat cell alpha 2-ARs, which largely outnumber beta-ARs in fat cells of certain fat deposits, in human and primate has never been clearly understood. The other AR type which is not linked to lipolysis regulation, the alpha 1-AR, is involved in the control of glycogenolysis and lactate production. Pharmacological approaches using in-situ microdialysis and selective alpha 2- and beta-AR agonists and antagonists have revealed sex- and tissue-specific differences in the adrenergic control of fat cell function and nutritive blood flow in the tissue surrounding the microdialysis probe.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Adipose tissue lipoprotein lipase and hormone-sensitive lipase. Contrasting findings in familial combined hyperlipidemia and insulin resistance syndrome.

The metabolism of free fatty acids (FFA) is altered in two common atherosclerosis-promoting disorders: familial combined hyperlipidemia (FCHL) and insulin resistance syndrome (IRS). It has been suggested that these two conditions may have a common etiology. The enzymes lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) are rate-limiting steps for the turnover of fatty acids in adipose tissue, because they hydrolyze extracellular triglycerides in lipoproteins (LPL) and intracellular triglycerides in adipocytes (HSL). The present study was undertaken to simultaneously determine the activities of LPL and HSL in subcutaneous adipose tissue from male patients with FCHL and IRS. LPL and HSL activity was investigated in 10 nonobese FCHL patients and compared with 10 matched healthy nonobese subjects, and in 8 essentially normolipidemic IRS patients (who did not have overt diabetes mellitus) and compared with 9 nonobese matched control subjects. LPL activity was 43% lower in patients with IRS (P < .0005), as compared with control subjects, but HSL activity was not significantly different in the two groups, On the other hand, HSL activity was decreased by 45% in FCHL patients (P < .01), as compared with control subjects, but LPL activity was not significantly different in FCHL patients and the control group. In conclusion, triglyceride metabolism in adipose tissue is altered in both FCHL and IRS. However, the abnormalities observed involve impaired function of LPL in IRS and impaired function of HSL in FCHL, suggesting separate etiologies for the altered lipolysis in these conditions, at least in male subjects.

Adipose Tissue↗
PubMed1997

Comparison of hormone-sensitive lipase activity in visceral and subcutaneous human adipose tissue.

The possible role of hormone-sensitive lipase (HSL) in determining regional differences in lipolysis activation in humans was studied in vitro. Small adipose tissue biopsies were obtained from the abdominal sc and omental regions during surgery in 21 subjects spanning a wide range of body mass index (22-50 kg/m2). In lipolysis experiments, isolated fat cells were incubated with lipolytic agents acting at different levels in the lipolytic cascade. The activity and messenger ribonucleic acid expression of HSL were determined. The maximum lipolytic capacity was higher in sc than in omental fat cells as were HSL activity and messenger ribonucleic acid expression. The maximum lipolysis rate was significantly correlated to HSL activity. This is in accordance with the role of HSL as the rate-limiting step of lipolysis. However, adipocytes were 24% larger in the sc than in the omental region, and the lipolysis rate was significantly correlated to fat cell size regardless of either the region of origin or gender. This indicates that the regulation of HSL activity in healthy subjects, which appears to occur at a transcriptional level, is to a large extent dependent on fat cell size.

Abdomen↗
PubMed1997

Adipose tissue lipolysis and hormone-sensitive lipase expression during very-low-calorie diet in obese female identical twins.

Eight pairs of obese female monozygotic twins were subjected to a 4-week, very-low-calorie diet (VLCD) that induced a decrease in mean body mass index from 32.9 +/- 1.1 to 29.7 +/- 1.1 kg/m2. Infusion of the beta-adrenergic agonist, isoproterenol, induced an increase in plasma levels of nonesterified fatty acids and glycerol that was more pronounced during than before VLCD. sc fat biopsies were obtained before and during VLCD to study adipocyte lipolysis. beta-adrenergic sensitivity was moderately improved during VLCD. Basal and stimulated lipolyses, and hormone-sensitive lipase activity and protein levels were increased during VLCD. Before VLCD, intrapair resemblance was found for basal and stimulated lipolysis rates. In response to the treatment, intrapair resemblance was observed for basal lipolysis and for lipolysis stimulated with agents acting on plasma membrane receptors. These results suggest that the increase of basal lipolysis during VLCD is caused by an increase of hormone-sensitive lipase expression. They support the notion that the genotype may play a role in regulating the changes of adipose tissue lipolysis rates observed during VLCD.

Adipose Tissue↗
PubMed1997

Site-specific regulation of gene expression by n-3 polyunsaturated fatty acids in rat white adipose tissues.

Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) limit abdominal fat depot hypertrophy. This could be due to regulation of the expression of proteins involved in adipose tissue metabolism. We investigated in vivo whether fatty acid synthase (FAS), hormone-sensitive lipase (HSL), lipoprotein lipase (LPL), phosphoenolpyruvate carboxykinase (PEPCK), CCAAT/enhancer binding protein alpha (C/EBP alpha), and leptin mRNA levels are affected in retroperitoneal (RP) and subcutaneous adipose tissues (SC) of rats fed n-3 PUFAs. For 4 weeks rats were fed high fat diets (20% fat) containing n-3 PUFAs given as eicosapentaenoic acid (EPA group), docosahexaenoic acid (DHA group), a mixture of these two fatty acids (MIX group), or native fish oil (FO group). A control group was fed with lard plus olive oil (LOO group). Final mean fat cell weight in RP ranged according to: LOO > or = EPA > or = DHA = FO = MIX. There was no difference in fat cell size of SC when comparing the LOO and MIX groups. The fatty acid compositions of RP and SC were similar and resemble that of dietary fat within each experimental group. In RP and compared to the LOO group, FAS, HSL, PEPCK, LPL, C/EBP alpha, and leptin mRNA levels decreased although not significantly in the EPA group, and were 40-75% lower in the DHA and MIX groups. mRNA levels were positively correlated to fat cell size in RP. In contrast, n-3 PUFAs had no effect on gene expression in SC. We conclude that n-3 PUFAs and mainly 22:6n-3 affect gene expression in a site-dependent manner in white adipose tissues via possible antiadipogenic effects.

Adipose Tissue↗
PubMed1996

Inhibition of hormone-sensitive lipase gene expression by cAMP and phorbol esters in 3T3-F442A and BFC-1 adipocytes.

Hormone-sensitive lipase (HSL) catalyses the rate-limiting step in adipocyte lipolysis. Short-term hormonal regulation of HSL activity is well characterized, whereas little is known about the control of HSL gene expression. We have measured HSL mRNA content of 3T3-F442A and BFC-1 adipocytes in response to the cAMP analogue 8-(4-chlorophenylthio)-cAMP (8-CPT-cAMP) and to the phorbol ester phorbol 12-myristate 13-acetate (PMA) by Northern blot, using a specific mouse cDNA fragment. Treatment of the cells for 12 or 6 h with, respectively, 0.5 mM 8-CPT-cAMP or 1 microM PMA produced a maximal decrease of about 60% in HSL mRNA. These effects were unaffected by the protein-synthesis inhibitor anisomycin, suggesting that cAMP and PMA actions were direct. The reduction in HSL mRNA was accompanied by a reduction in HSL total activity. The intracellular routes that cAMP and PMA follow for inducing such an effect seemed clearly independent. (i) After desensitization of the protein kinase C regulation pathway by a 24 h treatment of the cells with 1 microM PMA, PMA action was abolished whereas cAMP was still fully active. (ii) Treatment with saturating concentrations of both agents produced an additive effect. (iii) The synthetic glucocorticoid dexamethasone had no proper effect on HSL gene expression but potentiated cAMP action without affecting PMA action. cAMP inhibitory action on HSL is unexpected. Indeed, the second messenger of catecholamines is the main activator of HSL by phosphorylation. We envision that a long-term cAMP treatment of adipocytes induces a counter-regulatory process that reduces HSL content and, ultimately, limits fatty acid depletion from stored triacylglycerols.

3T3 Cells↗
PubMed1996

Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase.

By catalyzing the rate-limiting step in adipose tissue lipolysis, hormone-sensitive lipase (HSL) is an important regulator of energy homeostasis. The role and importance of HSL in tissues other than adipose are poorly understood. We report here the cloning and expression of a testicular isoform, designated HSLtes. Due to an addition of amino acids at the NH2-termini, rat and human HSLtes consist of 1068 and 1076 amino acids, respectively, compared to the 768 and 775 amino acids, respectively, of the adipocyte isoform (HSLadi). A novel exon of 1.2 kb, encoding the human testis-specific amino acids, was isolated and mapped to the HSL gene, 16 kb upstream of the exons encoding HSLadi. The transcribed mRNA of 3.9 kb was specifically expressed in testis. No significant similarity with other known proteins was found for the testis-specific sequence. The amino acid composition differs from the HSLadi sequence, with a notable hydrophilic character and a high content of prolines and glutamines. COS cells, transfected by the 3.9-kb human testis cDNA, expressed a protein of the expected molecular mass (M(r) approximately 120,000) that exhibited catalytic activity similar to that of HSLadi. Immunocytochemistry localized HSL to elongating spermatids and spermatozoa; HSL was not detected in interstitial cells.

Amino Acid Sequence↗
PubMed1996

Functional beta3-adrenoceptor in the human heart.

Beta3-adrenoceptors are involved in metabolism, gut relaxation, and vascular vasodilation. However, their existence and role in the human heart have not been documented. We investigated the effects of several beta-adrenoceptor agonists and antagonists on the mechanical properties of ventricular endomyocardial biopsies. In the presence of nadolol, a beta1- and beta2-adrenoceptor antagonist, isoprenaline produced consistent negative inotropic effects. Similar negative inotropic effects also resulted from the action of beta3-adrenoceptor agonists with an order of potency: BRL 37344 > SR 58611 approximately CL 316243 > CGP 12177. The dose-response curve to BRL 37344-decreasing myocardial contractility was not modified by pretreatment with nadolol, but was shifted to the right by bupranolol, a nonselective beta-adrenoceptor antagonist. Beta3-adrenoceptor agonists also induced a reduction in the amplitude and an acceleration in the repolarization phase of the human action potential. Beta3-adrenoceptor transcripts were detected in human ventricle by a polymerase chain reaction assay. These results indicate that: (a) beta3-adrenoceptors are present and functional in the human heart; and (b) these receptors are responsible for the unexpected negative inotropic effects of catecholamines and may be involved in pathophysiological mechanisms leading to heart failure.

Action Potentials↗
PubMed1996

Adipocyte lipolysis in normal weight subjects with obesity among first-degree relatives.

In this study we investigated whether fat cell lipolysis could be involved in the aetiology of obesity by comparing non-obese subjects with (Hob) or without (Hnorm) a family trait for overweight. A family history of obesity was present when at least one of the first-degree relatives had body mass index of 27 kg/m2 or more. Twenty-seven healthy, drug-free non-obese adult subjects were investigated; 13 were Hob and the remaining 14 were Hnorm. Eleven Hob had at least one obese parent. Isolated fat cells from abdominal subcutaneous adipose tissue were incubated in vitro. Glycerol release (lipolysis index), mRNA levels and enzymatic activity of hormone-sensitive lipase and radioligand binding to beta 1- and beta 2-adrenoceptors were determined. The lipolytic effects of noradrenaline (major endogenous lipolytic agent), isoprenaline (a non-selective beta-adrenoceptor agonist), forskolin (a direct activator of adenylyl cyclase) and dibutyryl cyclic AMP (activating protein kinase and thereby hormone-sensitive lipase) were reduced by about 50% (p from 0.001 to 0.01). The maximum activity of hormone-sensitive lipase was reduced 50% in Hob (p < 0.05) and correlated with the lipolytic responsiveness of fat cells in the whole population (r = 0.71). However, there was no difference between the groups in steady-state mRNA levels for the enzyme. Beta 1-->, beta 2- and alpha 2-adrenoceptor sensitivity as well as beta 1- and beta 2-adrenoceptor numbers were normal in Hob. Fasting plasma insulin was 49.1 and 32.6 pmol/l, respectively in Hob and Hnorm (p = 0.01). There was, however, no significant correlation between lipolysis in vitro and plasma insulin. Thus, lipolytic catecholamine resistance in fat cells, at least partly due to impaired function of hormone-sensitive lipase, is an adipocyte abnormality associated with a family tendency to obesity.

Adipocytes↗
PubMed1996

Detection of an amino acid polymorphism in hormone-sensitive lipase in Japanese subjects.

Hormone-sensitive lipase (HSL) plays an important role in energy metabolism by controlling the hydrolysis of triglycerides stored in adipose tissue. To investigate whether mutations in the HSL gene are associated with non-insulin-dependent diabetes mellitus (NIDDM), we screened for mutations of this gene using single-stranded conformation polymorphism (SSCP) in 35 Japanese subjects with NIDDM. SSCP analysis identified a variant pattern in axon 4, and the sequence showed that this variant pattern resulted from amino acid polymorphism (Arg309Cys). Subsequent study showed that this polymorphism was found in 18 of 151 NIDDM patients and 10 of 97 nondiabetic subjects, but allele frequency was not significantly different between the two groups (P = .7). Body mass index, serum triglyceride, and high-density lipoprotein (HDL) cholesterol were not different in subjects with and without the polymorphism. But serum total cholesterol was higher in subjects with the polymorphism than in subjects without it (P = .0005). These data indicate that this HSL polymorphism is not associated with NIDDM, obesity, and serum triglyceride level. However, an effect of the polymorphism to elevate serum total cholesterol has not been excluded, although further study is necessary to resolve its association with cholesterol metabolism.

Alleles↗
PubMed1996

Influence of prolactin on in vivo and in vitro lipolysis in rabbits.

Three experiments were conducted to assess the influence of prolactin on lipolysis in rabbits. In vivo, a single injection of 1 mg of ovine prolactin induces increased plasma glycerol and nonesterified fatty acids concentrations within 30 min (P < 0.01). On the contrary, in vitro, oPRL did not stimulate glycerol release in isolated adipocytes at physiological concentrations (under 10(-8) M). In a third experiment, the effect of chronic hyperprolactinemia on the adrenergic control of lipolysis was studied (daily subcutaneous injections of 1 mg ovine prolactin for 12 days). The weight of perirenal adipose tissue at the end of the period of injections was 27% lower in the prolactin-injected (PRL) rabbits than in the control (CTL) rabbits (88 +/- 15 g vs. 120 +/- 25 g; P < 0.05). Food intake during the period of injections was 28% lower in the PRL group than in the CTL group (177 +/- 21 g/d vs. 246 +/- 13 g/d; P < 0.05). Basal glycerol release was 157% higher in adipocytes from PRL rabbits than in those from CTL rabbits (P < 0.05). Stimulation of lipolysis with different adrenergic agonists was similar in both groups. These results suggested an indirect influence of prolactin on adipose tissue lipolysis in rabbits, but mechanisms implicated in this effect remain to be elucidated.

Adipocytes↗
PubMed1996

Beta 3-adrenoceptor in guinea pig brown and white adipocytes: low expression and lack of function.

In the guinea pig, cold acclimation induced a conversion of unilocular to multilocular adipocytes in interscapular (IS) and retroperitoneal (RP) fat depots but not in the epididymal (EP) fat pad. The conversion was associated with an increase in mitochondriogenesis and the appearance of the uncoupling protein. The maximal lipolytic responses to norepinephrine and dibutyryl adenosine 3',5'-cyclic monophosphate were decreased in IS cells, unchanged in RP cells, and increased in EP cells, suggesting a site-specific regulation of lipolysis at the postreceptor level. beta 3-Adrenergic agonists were not lipolytic regardless of the depot and the thermal environment of the animal. These agents did not inhibit glucose transport and lipogenesis, as was previously reported for rodents. Cloning and sequencing of the guinea pig beta 3-adrenoceptor gene revealed a slightly higher amino acid sequence similarity with the human than with the rodent beta 3-adrenoceptors. beta 3-Adrenoceptor transcripts were present at a very low level in guinea pig adipocytes, and mRNA levels did not increase to a significant extent after cold acclimation. The guinea pig thus differs from rodents by an absence of beta 3-adrenergic effects and by low beta 3-adrenoceptor expression in brown and white adipose tissues.

Acclimatization↗
PubMed1996

Expression of beta3-adrenoceptors with low lipolytic action in human subcutaneous white adipocytes.

Beta3-Adrenoceptors are involved in the control of catecholamine-induced lipolysis in rodent adipose tissues. The expression and function of human beta3-adrenoceptors were investigated in subcutaneous white adipocytes of young healthy women. In these cells, beta3-adrenoceptor mRNAs represent 20% of total amount of beta-adrenoceptor transcripts and less than half of beta1-adrenoceptor transcripts. Among beta3-agonists known to stimulate beta3-adrenoceptor-mediated lipolysis in rodent fat cells, only CGP12177 was able to mediate such activity in human fat cells. In in vitro lipolysis experiments and in situ microdialysis studies, CGP12177 had a 4- to 5-times lower lipolytic efficacy than isoprenaline, a nonselective beta-adrenoceptor agonist. CGP12177-induced lipolysis was antagonized in vitro by bupranolol, a beta-adrenergic antagonist potent on rodent beta3-adrenoceptors but not by nadolol, a beta1- and beta2-adrenoceptor antagonist. The in vitro blockade of isoprenaline-stimulated lipolysis by nadolol showed that the agonist acted solely via beta1- and beta2-adrenoceptors. Isoprenaline and CGP12177 were able to increase the nutritive blood flow suggesting an interaction of these molecules with receptors present in adipose tissue vessels. In conclusion, beta3-adrenoceptors are expressed in human subcutaneous white adipocytes but do not significantly contribute to isoprenaline-induced lipolysis.

Adipocytes↗
PubMed1996

Regulation of lipolysis in fat cells of obese women during long-term hypocaloric diet.

OBJECTIVE: To investigate the influence of four weeks treatment with a strictly defined very low calorie diet (VLCD) on the regulation of adipocyte matabolism in vitro in subcutaneous fat cells of obese subjects. DESIGN: Prospective study. SUBJECTS: Nine obese, but otherwise healthy and drug-free women aged 26-48 years with BMI 36.4-51.9 kg/m2 were investigated before and during the fourth week on a calorie restricted diet. MEASUREMENTS: A subcutaneous adipose tissue biopsy was obtained from the abdominal area. Isolated fat cells were prepared and incubated in vitro with different agents acting on lipolysis at defined steps in the lipolytic cascade. Glycerol (lipolytic index), hormone-sensitive lipase activity and incorporation of glucose into lipids were measured. RESULTS: VLCD caused a two-fold rise in basal lipolysis (p < 0.005). In spite of this, the maximal lipolytic response of noradrenaline, isoprenaline (non-selective beta-adrenoceptor agonist), dobutamine (beta 1-adrenoceptor agonist), terbutaline (beta 2-adrenoceptor agonist), CGP 12177 (beta 3-adrenoceptor agonist), forskolin (stimulating adenylyl cyclase), dibuturyl cyclic AMP and 8-bromo cyclic AMP (cyclic AMP analogues resistant or sensitive to phosphodiesterase, respectively) were maintained. No differences were found in the hormone-sensitive lipase activity before or during VLCD. The specific alpha 2-adrenoceptor agonist UK 14304 was equally effective in inducing antilipolysis both before and during calorie restriction. However, during VLCD, the sensitivity and maximal antilipolytic effect of insulin were significantly reduced (p < 0.05) and the ability of insulin to stimulate lipogenesis was almost completely blunted. CONCLUSIONS: Four weeks of VLCD induced elevated basal lipolysis, a resistance to the ability of insulin to induce antilipolysis and lipogenesis in subcutaneous fat cells, but preserved lipolytic catecholamine action. These are factors that together promote fat mobilization and thereby weight reduction during long-term calorie restriction.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Expression of hormone-sensitive lipase in the human colon adenocarcinoma cell line HT29.

Hormone-sensitive lipase expression was studied in the human colon adenocarcinoma cell line, HT29. Diacylglycerol lipase and cholesterol esterase [corrected] activities in HT29 cells were inhibited by known inhibitors of hormone-sensitive lipase (diethyl-p-nitrophenyl phosphate, NaF and HgCl2) to the same extent as in human adipocytes. A polyclonal antiserum directed against rat hormone-sensitive lipase inhibited 89% of HT29 cell lipase activity. HT29 hormone-sensitive lipase was the same size as the adipocyte enzyme as was its mRNA. Complete homology between mRNA sequences in HT29 and adipocyte was demonstrated using ribonuclease protection assay. These data are consistent with the expression of a protein closely related, if not identical, to the enzyme expressed in human adipose tissue. HT29 is the first human cell line where hormone-sensitive lipase expression has been shown.

Adenocarcinoma↗
PubMed1995

Adrenergic receptors and fat cells: differential recruitment by physiological amines and homologous regulation.

The control of fat cell lipolysis by the catecholamines involves at least four different adrenoceptor subtypes; three beta (beta 1-, beta 2-, and beta 3-ARs) and one alpha 2-adrenoceptor (alpha 2-AR). The physiological importance of the beta- and alpha 2A-ARs varies according to the species, the sex, the age, the anatomical location of fat deposits and the degree of obesity in humans and animals. The physiological amines operate through differential recruitment of these sites on the basis of their relative affinities. This point has been assessed by in vitro studies and has partly been confirmed in in vivo experiments using selected alpha/beta-AR antagonists and in situ microdialysis. The affinity of the beta 3-AR for catecholamines is less than that of the classical beta 1- and beta 2-ARs in the various species investigated. Conversely, it is the alpha 2-AR which exhibit the highest affinity for the physiological amines in all fat cells. The relative order of affinity of the various fat cell ARs for the physiological amines defined in binding studies and in vitro assays is alpha 2 > beta 1 > or = beta 2 > beta 3 for norepinephrine and alpha 2 > beta 2 > beta 1 > beta 3 for epinephrine. When considering differential beta-AR recruitment by catecholamines, it is the beta 1-AR which is always activated at the lowest norepinephrine levels, whatever the species, while the activation of the beta 3-AR requires higher norepinephrine levels. In addition to the differential recruitment, differential regulation by hormones could also occur for each fat cell AR subtype. The alpha 2-and beta 3-ARs are less prone to desensitization and down-regulation by comparison with the beta 1- and beta 2-AR.

Adipocytes↗