The Experts below are selected from a list of 11040 Experts worldwide ranked by ideXlab platform
Toshihide Yoshida - One of the best experts on this subject based on the ideXlab platform.
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The knack of treatment for obese patients with hypertension and diabetes mellitus: combined the newest tailor-made diet therapy with the usual stress-management therapy
Nihon rinsho. Japanese journal of clinical medicine, 2003Co-Authors: Toshihide YoshidaAbstract:The 5-10% body weight loss often leads to amelioration or cure of hypertension and diabetes mellitus in obese patients. But, the effect of diet therapy on obese patients differs in each individual because of the differences in energy expenditure, such as the resting metabolic rate (RMR). We have recently reported that obese Japanese with the missense mutation (Trp64Arg) of the beta 3-Adrenergic Receptor (beta 3-AR) gene and/or the uncoupling protein 1 (UCP1) gene mutation (A-3826G) have difficulties in weight loss by the reducing RMR, while Japanese with beta 2-AR gene mutation (Arg16Gly) have an under-weight condition through increased RMR. Here I introduce the importance of tailor-made diet therapy to improve obesity based on analysis of gene polymorphisms and in order to maintain this tailor-made diet therapy, I emphasize that the stress-management therapy should be needed to remove mental problems which caused obesity.
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The tailor-made diet therapy to improve obesity
Nihon rinsho. Japanese journal of clinical medicine, 2002Co-Authors: Yasuto Takakura, Toshihide YoshidaAbstract:As the white adipose tissue, especially abdominal fat is an endocrine organ secreting adipocytokines, which induce insulin resistance, hypertension, and arteriosclerotic diseases, reduction of the abdominal fat is important. But effect of the diet therapy differs in each individual, because of the difference of energy expenditure. Since the relationship between the missense mutation (Trp64Arg) of the beta 3-Adrenergic Receptor (beta 3-AR) gene and low energy expenditure in the obese Pima Indians was made clear, gene polymorphisms that mediate body weight are reported one after another. We also reported that one third of Japanese have the Trp64Arg mutation of beta 3-AR gene, which may produce obesity or difficulties in weight loss. Here we introduce the obesity-related genes, and report the importance of Tailor-made diet therapy based on molecular genetics to improve obesity.
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Beta 3-Adrenergic Receptor agonists--past, present and future
Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 2001Co-Authors: Yasuto Takakura, Toshihide YoshidaAbstract:beta 3-Adrenergic Receptors (beta 3-AR) play an important role in the thermogenesis in brown adipose tissue and lipolysis in white adipose tissue. beta 3-AR agonists developed in the early stages produced marked weight reduction and an anti-diabetic effect in rats and mice, but did not in humans, because of the difference in the chemical structure of the beta 3-AR. In 1995, a naturally occurring variant (Trp64Arg) of the human beta 3-AR gene was shown to be correlated with obesity and insulin resistance in Pima Indians. Moreover, the fact that white adipocytes produce various hormones and cytokines that cause life-style-related disease was recently made clear. Because the reduction of the visceral fat is thought to be important to prevent these diseases, the expectations for the human beta 3-AR agonist having a novel anti-obesity effect are rising. Some interesting findings were recently reported with beta 3-AR agonists: the difference of the lipolysis was dependent on the existence of the Trp64Arg mutation and the up-regulation effect of the UCP1 and beta 3-ARs themselves in the adipose tissue and skeletal muscle. Therefore, we introduce informations (past, present and future) on beta 3-AR agonists in this paper.
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Beta 3 Adrenergic Receptor polymorphism and obesity
Nihon rinsho. Japanese journal of clinical medicine, 1998Co-Authors: Toshihide Yoshida, Umekawa TAbstract:: The beta 3-adrenoceptor plays a significant role in the control of lipolysis and thermogenesis in the brown adipose tissue of rodents and humans. In human beta 3-adrenoceptor, a Trp to Arg replacement has recently been discovered. This change which occurs at position 64, in the first coding exon, has been correlated with increased weight gain, difficulty in losing weight, insulin resistance syndrome, and worsened diabetic situation. Higher percentages of this mutation are observed in Pima Indians (over 30%) and Japanese (20%). The possible functional mechanism of Trp54Arg is reported using human HEK293 cell line stably expressing the wild type and the [Arg64] beta 3-adrenoceptor type. Beta 3-adrenoceptor agonists available for humans are been also developing. In this paper we describe these points up-to-date.
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Anti-obesity effects of selective agonists to the beta 3-Adrenergic Receptor in dogs. I. The presence of canine beta 3-Adrenergic Receptor and in vivo lipomobilization by its agonists.
The Journal of veterinary medical science, 1998Co-Authors: Noriyasu Sasaki, Toshihide Yoshida, Eiji Uchida, Masayoshi Niiyama, Masayuki SaitoAbstract:It is known that in rodents and humans the beta 3-Adrenergic Receptor (beta 3-AR) is present primarily in adipocytes and plays a significant role in the Adrenergic stimulation of lipolysis. We examined the expression of beta 3-AR mRNA in the dog and the lipomobilizing effects of beta 3-AR-selective agonists in vivo. Reverse transcription polymerase chain reaction of RNA extracted from dog adipose tissue produced a cDNA fragment, the nucleotide sequence of which was highly homologous to the corresponding regions of human (86.4%) and mouse (79.5%) beta 3-AR cDNA. The beta 3-AR mRNA was present at high levels in subcutaneous and visceral adipose tissues, but undetectable in other organs. When a selective beta 3-AR agonist, CL316,243, was infused intravenously into beagle dogs, the plasma level of free fatty acid increased in 30 min and persisted at higher levels for several hours. ICI D7114, another beta 3-AR agonist, also showed a similar lipomobilizing effect, but with lower potency. beta 3-AR agonist infusion also increased the plasma insulin level. These results suggested that functional beta 3-AR is present in adipose tissues of the dog and that it is effective for in vivo lipomobilization.
Arthur Donny Strosberg - One of the best experts on this subject based on the ideXlab platform.
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Stimulation of the Extracellular Signal-Regulated Kinase 1/2 Pathway by Human Beta-3 Adrenergic Receptor: New Pharmacological Profile and Mechanism of Activation
Molecular pharmacology, 1999Co-Authors: Cindy C. Gerhardt, Arthur Donny Strosberg, Jerome Gros, Tarik IssadAbstract:We present evidence that stimulation of the human Beta-3 Adrenergic Receptor (AR), expressed in Chinese hamster ovary/K1 cells, specifically activates the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK)1 and 2, but not JNK or p38. The extent and kinetics of the ERK stimulation by the Beta-3 AR are identical with those of the endogenic insulin Receptor. However, insulin augments cellular proliferation, whereas Beta-3 AR agonists inhibit proliferation due to the production of cyclic AMP. The pharmacological profile of the ERK activation by the Beta-3 AR differs significantly from its activation of adenylyl cyclase. The order of potency and intrinsic activities of both natural ligands, norepinephrine and epinephrine, is inversed between both signaling pathways. In addition, BRL 37344 and propranolol, ligands that act as agonists in the stimulation of cyclase, act as antagonists for ERK activation. The activation of ERK1/2 is sensitive to pertussis toxin, suggesting that the Beta-3 AR, in addition to its interaction with Gs, can couple to Gi/o. Furthermore, the activation of ERK by the Beta-3 AR is sensitive to PD98059, wortmannin, and LY294002, indicating a crucial role for mitogen-activated protein kinase kinase and phosphatidylinositol-3 kinase (PI3K), respectively. A Beta-3 AR-mediated stimulation of PI3K is confirmed by the observation that the selective agonist CGP 12177A specifically activates protein kinase B. As was observed for the activation of ERK, the activation of protein kinase B is inhibited by preincubation with pertussis toxin and PI3K inhibitors, suggesting that both are a consequence of a Gi/o-mediated activation of PI3K.
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STRUCTURE AND FUNCTION OF THE BETA 3-Adrenergic Receptor
Annual review of pharmacology and toxicology, 1997Co-Authors: Arthur Donny StrosbergAbstract:▪ Abstract The β3 subtype of adrenaline and noradrenaline Receptors has now been extensively characterized at the structural and functional levels. Ligand binding and adenylyl cyclase activation studies helped define a β-Adrenergic profile that is quite distinct from that of the β1-and β2-Adrenergic Receptors, but strongly reminiscent of most of the “atypical” responses reported in earlier pharmacologic studies. Human, other large mammal, and rodent Receptors share most of the characteristic β3 properties, although obvious species-specific differences have been identified. Recently, the incidence of a naturally occurring variant of the human β3-Adrenergic Receptor was shown to be correlated with hereditary obesity in Pima Indians and in Japanese individuals, and in Western obese patients with increased dynamic capacity to add on weight and develop non–insulin-dependent diabetes mellitus (NIDDM). A mild weight increase was also shown to develop in female, but not male, mice in which the β3 Receptor gene wa...
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Cell-specific down-regulation of the beta 3-Adrenergic Receptor.
The Journal of biological chemistry, 1994Co-Authors: F Nantel, Stefano Marullo, Stéphane Krief, Arthur Donny Strosberg, Michel BouvierAbstract:Previous studies have shown that beta 3-Adrenergic Receptors, in contrast to the beta 1 and beta 2 subtypes, do not undergo desensitization following short term activation (minutes) with agonists. Longer activation (hours) has been shown to induce desensitization of the beta 3-Adrenergic Receptor in some, but not all, cases, suggesting that cell- or species-specific mechanisms may be involved. We investigated the contribution of the cell type to the pattern of beta 3-Adrenergic Receptor long term desensitization by studying, in parallel, two cell lines (Chinese hamster fibroblasts and murine Ltk- cells) expressing the human beta 3-Adrenergic Receptor. Sustained agonist-promoted down-regulation of the beta 3-Adrenergic Receptor could be induced in Ltk- cells, whereas only a transient and weak reduction of Receptor number was observed in Chinese hamster fibroblasts. The half-life of the beta 3-Adrenergic Receptor was not affected by the agonist activation in either cell line, indicating that in contrast to the beta 2-Adrenergic Receptor, degradation of preexisting Receptor protein does not contribute to down-regulation. Sustained reduction of Receptor RNA levels, monitored by reverse transcriptase polymerase chain reaction, was exclusively shown in Ltk- cells and probably accounted for most of the observed down-regulation. Differences in the ability of the Receptor to stimulate adenylyl cyclase activity in the two cell lines may be responsible for the distinct patterns of beta 3-Adrenergic Receptor down-regulation.
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Transcriptional modulation by n-butyric acid of beta 1-, beta 2-, and beta 3-Adrenergic Receptor balance in 3T3-F442A adipocytes.
The Journal of biological chemistry, 1994Co-Authors: Stéphane Krief, Beatrice Baude, Arthur Donny Strosberg, Bruno Fève, Jacques Pairault, Vladimir Zilberfarb, L J EmorineAbstract:3T3-F442A adipocytes, which express major beta 3-Adrenergic Receptors (beta 3-AR) (90%) and minor beta 1-AR (< 10%) and beta 2-AR (< 1%) populations, were used to investigate regulation by n-butyric acid of beta-AR subtype expression. Following butyrate treatment, EC50 values of beta 1- and beta 2-selective agonists, dobutamine and fenoterol, were decreased, whereas that of the beta 3-selective agonist BRL37344 was increased. Direct binding and competition of (-)-[125I]iodocyanopindolol binding by selective beta 1- and beta 2-AR antagonists, CGP20712A and ICI118551, and by the beta 3-AR agonist, BRL37344, revealed that both beta 1- and beta 2-AR were increased in butyrate-treated adipocytes, whereas beta 3-AR almost totally disappeared. In control adipocytes, beta 1-, beta 2-, and beta 3-AR transcripts (quantitated by a polymerase chain reaction assay) represented 6.5, 0.5, and 93% of total beta-AR mRNA, respectively. In butyrate-exposed cells, proportions of beta-AR proteins and mRNAs were, respectively, 87 and 94% for beta 1 and 9 and 1% for beta 2-AR. beta 3-ARs were barely detectable in binding assays and accounted for 4.5% of beta-AR transcripts. Variations of beta-AR protein and mRNA levels were accompanied by parallel changes in the transcription rates of the corresponding genes. The differential regulation of the three beta-ARs by n-butyric acid, a dietary factor produced from colonic fermentation, may have significant nutritional and energetic consequences.
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The human beta 3-Adrenergic Receptor is resistant to short term agonist-promoted desensitization.
Molecular pharmacology, 1993Co-Authors: F Nantel, Arthur Donny Strosberg, Michel Bouvier, Hélène Bonin, L J Emorine, Vladimir Zilberfarb, Stefano MarulloAbstract:The human beta 3-Adrenergic Receptor (beta 3AR) lacks most of the structural determinants that, in the beta 2AR, contribute to agonist-induced Receptor desensitization. To evaluate the effect of these structural differences on the beta 3AR desensitization profile, the human beta 2- and beta 3AR were stably expressed in Chinese hamster fibroblasts (CHW) and murine Ltk- cells (L cells). Incubation of CHW-beta 2 or L-beta 2 cells with 10 microM isoproterenol for 30 min induced a decrease in the maximal agonist-stimulated adenylyl cyclase activity and a cAMP-dependent reduction in the potency of isoproterenol to stimulate the Receptor. In addition, this pretreatment impaired the formation of the high affinity heterotrimeric agonist-Receptor-guanine nucleotide-binding protein complex and induced the sequestration of approximately 30% of the beta 2AR away from the cell surface. In contrast, similar treatment of CHW-beta 3 and L-beta 3 cells did not affect the maximal Receptor-stimulated adenylyl cyclase activity, nor did it induce any significant sequestration of the beta 3AR. In fact, only a modest cAMP-independent decrease in the potency of isoproterenol to stimulate the Receptor could be observed after isoproterenol treatment. The rapid desensitization pattern of a chimeric beta 3AR, in which the third cytoplasmic loop and the carboxyl-terminal tail were exchanged with those of the beta 2AR (which include potential phosphorylation sites and other possible molecular determinants of desensitization), was found to be intermediate between those of the two original Receptor subtypes. These results demonstrate that (i) the beta 3AR is less prone than the beta 2AR to undergo rapid agonist-promoted desensitization and, (ii) in addition to the phosphorylation sites located in the third cytoplasmic loop and the carboxyl-terminal tail of the beta 2AR, other molecular determinants contribute to short term desensitization.
A.donny Strosberg - One of the best experts on this subject based on the ideXlab platform.
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Comparative expression of the human beta(2) and beta(3) Adrenergic Receptors in Saccharomyces cerevisiae.
Biochimica et biophysica acta, 2003Co-Authors: Catherine Duport, Jacqueline Loeper, A.donny StrosbergAbstract:The beta(3) Adrenergic Receptor (beta(3)AR) is the predominant beta subtype in human brown adipocytes and is essential for regulating thermogenic lipolysis. To establish a novel experimental system for the biochemical analysis of this protein, we engineered several yeast strains. We show that the sterol background of the host strain greatly modulates the beta(3)AR expression but not in the same way as it modulates the beta(2) Adrenergic Receptor (beta(2)AR), the other main studied adipocyte subtype. The human beta(3)AR expressed in yeast is N-glycosylated but not phosphorylated. This latter characteristic distinguishes it from the beta(2)AR. We showed that both beta(2)AR and beta(3)AR follow the secretory pathway to the yeast plasma membrane (PM) and are degraded in the vacuole. In the yeast strains used in this work, the two Receptors also share a common mechanism of direct signal transduction through the yeast G(alpha) protein, Gpa1p. These strains thus appear to be useful for biochemical and structural studies of the human beta(3)AR in an in vivo reconstitution system.
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Molecular Cloning and Pharmacological Characterization of the Bovine β3‐Adrenergic Receptor
European journal of biochemistry, 1995Co-Authors: Gerlinde Lenzen, A.donny Strosberg, Archana Kapoor, Marie‐françoise Drumare, Philippe Archimbault, Brian St John ManningAbstract:A full-length clone encoding a beta-Adrenergic Receptor was isolated from a bovine brown adipose tissue cDNA library. By comparative sequence analysis, and pharmacological characterization of a Chinese hamster ovary cell line expressing the full-length cDNA, it was shown that the product of the cloned gene is the bovine equivalent of the atypical beta 3-Adrenergic Receptor previously described in human, mouse, and rat [Strosberg, A. D. (1993) Prot. Sci. 2, 1198-1209]. The cloned Receptor exhibits a pharmacological profile very similar to those from other species. In particular, the Receptor has high affinity for BRL 37344 [(RR,SS)-(+/-)-4-(2'-[2-hydroxy-2-(3- chlorophenyl)ethylamino]propyl)phenoxyacetate sodium salt sesquihydrate], and low affinity for the iodinated ligand(-)-[3-125I]-iodocyanopindolol. The bovine beta 3-Adrenergic Receptor has high affinity for beta 1-Adrenergic Receptor and beta 2-Adrenergic Receptor antagonists including ICI 201651 [(R)-4-(2-hydroxy-3-phenoxypropylaminoethoxy)-N-(2- methoxyethyl)phenoxy acetic acid], carazolol, and CGP 12177A [(+/-)-4-(3-t-butylamino-2- hydroxypropoxy)benzimidazol-2-one]. In contrast to the murine beta 3-Adrenergic Receptor, both bupranolol and (-)-propranolol were partial agonists of the bovine Receptor. The isolation of the bovine beta 3-Adrenergic Receptor, and information obtained from detailed pharmacological profiling may allow for the development of selective compounds for producing beef cattle with a low-body-mass index, and also aid the ongoing search for more selective agonists for the human Receptor.
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Long term phorbol ester treatment down-regulates the beta 3-Adrenergic Receptor in 3T3-F442A adipocytes.
The Journal of biological chemistry, 1995Co-Authors: Bruno Fève, Khadija El Hadri, Marie-franoise Drumare, A.donny StrosbergAbstract:The role of protein kinase C (PKC) in the regulation of the beta 3-Adrenergic Receptor (beta 3-AR) gene was examined in murine 3T3-F442A adipocytes, which express this Receptor subtype at a high level. We also investigated the involvement of this kinase in the modulation of beta 3-AR gene expression by insulin. Long term exposure of 3T3-F442A adipocytes to phorbol 12-myristate 13-acetate (PMA) decreased beta 3-AR mRNA content in a time- and concentration-dependent manner, with maximal changes observed at 6 h (6.5-fold decrease) and at 100 nM PMA. This inhibition was selective for beta 3-AR transcripts, since beta 1- and beta 2-AR mRNA content remained unchanged. Also, (-)-[125I]cyanopindolol saturation and competition binding experiments on adipocyte membranes indicated that PMA induced an approximately 2-fold decrease in beta 3-AR expression, while that of the two other subtypes was not affected. This correlated with a lower efficacy of beta 3-AR agonists to stimulate adenylyl cyclase. Conversely, long term exposure to PMA did not alter adenylyl cyclase activity in response to guanosine 5'-O-(3-thiotriphosphate) or forskolin. The inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate did not repress beta 3-AR mRNA levels. Inhibition of beta 3-AR mRNA by PMA was suppressed by the PKC-selective inhibitor bisindolylmaleimide, and was not observed in PKC-depleted cells, indicating that PKC was involved in this response. mRNA turnover experiments showed that the half-life of beta 3-AR transcripts was not affected by long term PMA exposure. When 3T3-F442A adipocytes were pretreated with PMA for 24 h to down-regulate PKC, or with bisindolylmaleimide, the insulin-induced inhibition of beta 3-AR mRNA levels was reduced by 44-67%. These findings demonstrate that sustained PKC activation exerts a specific control of beta 3-AR gene expression and is involved, at least in part, in the modulation by insulin of this Adrenergic Receptor subtype.
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The promoter and intron/exon structure of the human and mouse β3‐Adrenergic‐Receptor genes
European journal of biochemistry, 1993Co-Authors: A Van Spronsen, A.donny Strosberg, Stéphane Krief, Clara Nahmias, Marie-madeleine Briend-sutren, L J EmorineAbstract:Transcription-start sites for the mouse and human beta 3-Adrenergic-Receptor mRNA have been localized in a region comprised between 150 and 200 nucleotides 5' from the ATG translation-start codon. Motifs potentially implicated in heterologous regulation of beta 3-Adrenergic-Receptor expression by glucocorticoids and by beta-Adrenergic agonists have been identified upstream from these cap sites. In mouse, a second mRNA initiation region is postulated to exist further upstream. Comparison of the nucleotide sequences of the 3' end of the human and mouse beta 3-Adrenergic-Receptor genes to those of the corresponding cDNA revealed that in contrast to beta 1 and beta 2 Adrenergic Receptors, the beta 3-Adrenergic-Receptor genes comprise several exons. A large exon (1.4 kb) encodes the first 402 and 388 amino-acid residues of the human and mouse beta 3 Adrenergic Receptor, respectively. In man, a second exon (700 bp) contains the sequence coding for the six carboxy-terminal residues of the Receptor and the entire mRNA 3' untranslated region. In mouse, a second exon (68 bp) codes for the 12 carboxy-terminal residues of the Receptor and a third exon contains the beta 3-Adrenergic-Receptor mRNA 3' untranslated region. The use of alternate acceptor splice sites generates two forms of exon 3 (600 bp and 700 bp), yielding two beta 3-Adrenergic-Receptor transcripts which are differentially expressed in white and brown adipose tissues. Human beta 3-Adrenergic-Receptor transcripts with different 3' untranslated regions are produced by continuation of transcription beyond termination signals. Together, our results suggest that utilization of alternate promoters and/or 3' untranslated regions may allow tissue-specific regulation of beta 3-Adrenergic-Receptors expression.
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Tissue distribution of beta 3-Adrenergic Receptor mRNA in man.
The Journal of clinical investigation, 1993Co-Authors: Stphane Krief, F Lönnqvist, Beatrice Baude, A Van Spronsen, Serge Raimbault, Daniel Ricquier, A.donny Strosberg, Peter Arner, Laurent Jean EmorineAbstract: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.
Daniel Ricquier - One of the best experts on this subject based on the ideXlab platform.
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polymorphisms of uncoupling protein ucp and beta 3 adrenoReceptor genes in obese people submitted to a low calorie diet
International Journal of Obesity, 1996Co-Authors: Frederic Fumeron, Daniel Ricquier, I Durackbown, D Betoulle, Annemarie Cassarddoulcier, S Tuzet, Frederic Bouillaud, J C Melchior, M ApfelbaumAbstract:OBJECTIVE To investigate whether the genetic polymorphisms of the uncoupling protein (UCP) and beta 3 Adrenergic Receptor (beta 3 AR) were associated with differences of weight loss in obese patients submitted to a low calorie diet. DESIGN Longitudinal, clinical intervention study of a 25% restriction in energy intake with respect to genotypes. SUBJECTS 163 patients with a body mass index above 27. MEASUREMENTS Body weight and body mass index at baseline and after 2.5 months, genotypes by polymerase chain reaction followed by enzymatic digestion. RESULTS For the UCP polymorphism, two alleles, 1 and 2 were identified with respective frequencies of 0.27 and 0.73. The allele 1 was associated with lower body weight loss after diet: 4,6,5.7 and 7.1 kg for the 1-1, 1-2 and 2-2 genotypes respectively (P < 0.05). No difference in weight loss was found according to the beta 3 AR Trp64Arg mutation. CONCLUSIONS A genetic variant of the UCP gene is associated with a resistance to low calorie diet. This result, together with previous data on body weight gain, supports the hypothesis of a role of UCP and brown adipose tissue in the body weight regulation in humans. The importance of the Trp64Arg mutation of the beta 3 AR in the resistance to low calorie diet is still to demonstrate.
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Tissue distribution of beta 3-Adrenergic Receptor mRNA in man.
The Journal of clinical investigation, 1993Co-Authors: Stphane Krief, F Lönnqvist, Beatrice Baude, A Van Spronsen, Serge Raimbault, Daniel Ricquier, A.donny Strosberg, Peter Arner, Laurent Jean EmorineAbstract: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.
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beta 3 Adrenergic Receptor stimulation restores message and expression of brown fat mitochondrial uncoupling protein in adult dogs
Proceedings of the National Academy of Sciences of the United States of America, 1991Co-Authors: Odette Champigny, Daniel Ricquier, Olivier Blondel, Rachel M Mayers, Martyn G Briscoe, Brian Roy HollowayAbstract:Abstract Brown adipose tissue (BAT) is present throughout life in rodents and plays an important role in energy balance. However, whereas BAT is clearly recognizable in the neonates of larger mammals (including dogs, cats, sheep, cattle, and humans), it is undetectable or present in only small quantities in adults of these species and is replaced by a tissue with the gross characteristics of white adipose tissue. Here we provide evidence that treatment of adult dogs with a beta 3-Adrenergic Receptor agonist (ICI D7114) that has thermogenic and antiobesity properties leads to the appearance of BAT at several anatomical sites. The presence of BAT was primarily demonstrated by monitoring the inner mitochondrial membrane uncoupling protein and its mRNA, which are unique to the tissue. Neither message nor protein was detected in adipose tissue samples from control dogs but both were detected in samples from dogs treated with ICI D7114. The data suggest that stimulation of beta 3-Adrenergic Receptors can reactivate nascent BAT (which has the appearance of white adipose tissue) by increasing expression of the gene coding for uncoupling protein or lead to the recruitment of fully differentiated BAT from preadipocyte precursor cells.
Peter Arner - One of the best experts on this subject based on the ideXlab platform.
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Phenotypic characterization of the Trp64Arg polymorphism in the beta 3-Adrenergic Receptor gene in normal weight and obese subjects.
Diabetologia, 1996Co-Authors: Lönnqvist F, Luthman H, Peter ArnerAbstract:Abstract The beta 3-Adrenergic Receptor, located mainly in fat cells of visceral adipose tissue, is involved in the regulation of lipolysis and thermogenesis. Recently, a mutation in the corresponding gene resulting in the replacement of tryptophan by arginine in position 64 (Trp64Arg) has been demonstrated, which associated with obesity and metabolic complications of obesity. We have investigated whether this polymorphism is associated with changes in beta 3-Adrenergic Receptor function or clinical characteristics in 40 non-obese and 43 obese non-diabetic subjects who underwent elective abdominal surgery. The beta-Adrenergic Receptor gene polymorphism was examined by restriction-enzyme cleavage conformation. Beta 3-Adrenergic Receptor function was investigated by measuring lipolysis in isolated visceral white fat cells incubated with noradrenaline (natural ligand) or (CGP) 12,177 (selective beta 3-agonist). No homozygotes for the mutation were found. The allelic frequency of Trp64Arg was similar in obese and non-obese subjects (9.4 and 12.5%, respectively). In obese and non-obese subjects there was no change in body mass index, body fat distribution, fat cell size, fasting circulating levels of insulin, glucose or lipids, blood pressure or adipocyte lipolysis induced by noradrenaline or CGP 12,177 when Trp64Arg heterozygotes were compared with Trp64A homozygotes. Our results suggest that the Trp64Arg mutation in its heterozygous form is not a major determinant of beta 3-Adrenergic Receptor function (when assessed by lipolysis in white adipose tissue) or of the pathophysiology of obesity.
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Tissue distribution of beta 3-Adrenergic Receptor mRNA in man.
The Journal of clinical investigation, 1993Co-Authors: Stphane Krief, F Lönnqvist, Beatrice Baude, A Van Spronsen, Serge Raimbault, Daniel Ricquier, A.donny Strosberg, Peter Arner, Laurent Jean EmorineAbstract: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.