μ3-Adrenoceptor: an update

Giacobino, Jean-Paul

doi:10.1530/eje.0.1320377

Cited by 105 publications

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“…The /?3-adrenergic receptor is predominantly expressed in adipose tissue and plays an important role in lipid metabolism and metabolic rate (18,19). Thus, molecular abnormalities of /93 adrenergic receptor are expected to lead to obesity and insulin resistance (18,19), and therefore, the ADRB3 gene is a strong candidate gene for insulin resistance in hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, molecular abnormalities of /93 adrenergic receptor are expected to lead to obesity and insulin resistance (18,19), and therefore, the ADRB3 gene is a strong candidate gene for insulin resistance in hypertension. In fact, a Trp64Arg mutation in the ADRB3 gene has been suggested to be associated with higher diastolic blood pressure as well as with clinical features of the insulin resistance syndrome (5).…”

Section: Discussionmentioning

confidence: 99%

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Analysis of Candidate Genes for Insulin Resistance in Essential Hypertension

et al. 1996

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To clarify the genetic basis of insulin resistance in hypertension, case-control association studies were performed to examine candidate genes for insulin resistance in hypertension. Since the main site of insulin resistance in hypertension is glycogen synthesis in skeletal muscle, genes that encode molecules involved in this pathway, i.e. insulin receptor (INSR), insulin-responsive glucose transporter (GLUT4) and glycogen synthase (GSY), were studied. In addition, since recent studies suggest the contribution of /93 adrenergic receptor to the insulin resistance syndrome, the gene encoding ~3 adrenergic receptor (ADRB3) was also studied. Frequency of homozygotes for common C allele of a microsatellite polymorphism in the INSR gene was higher in the hyperinsulinemia group, but not in the normoinsulinemia group of hypertensive patients than in normotensive control subjects. Insulin sensitivity, however, was not significantly different between hypertensive patients with C/C genotype and those without this genotype. No significant differences were observed in the distribution of alleles or genotypes of the GLUT4, GSY and ADRB3 genes between hyperinsulinemia and normoinsulinemia groups of hypertensive patients or between these groups and the control group. These data suggest that the INSR polymorphism is associated with hyperinsulinemia, but not with insulin resistance, in hypertension. (Hypertens Res 1996; 19 Suppl. I: S31-S34)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Analysis of Candidate Genes for Insulin Resistance in Essential Hypertension

et al. 1996

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“…In humans, the ß3-adrenoceptor is expressed in newborn baby BAT, although at a relatively lower level in comparison to the ß1/ßrsubtypes than in rodent BAT (18) and the question of its existence or not in WAT is controversial. No, or only a very low expression of ß3-adrenoceptor mRNA could be detected in various human WAT depots (9). A role of the ß3-adrenoceptor in the control of lipolysis in WAT has also been difficult to prove.…”

Section: The ßTadrenoceptor -Ucp1 Ax/smentioning

confidence: 99%

Section: The ßTadrenoceptor -Ucp1 Ax/smentioning

confidence: 99%

“…This third subtype called the ß3-adrenoceptor was found to be the predominant ß-subtype in rodent BAT and white adipose tissue (WAT) (8,9). When the BAT sympathetic nervous system activity is increased by cold exposure or overfeeding, the stimulatory effect on UCP1 activity and expression is therefore mediated essentially by the ß3-adrenoceptor (9). Therefore, the ß3-adrenoceptor-UCP1-axis is a major determinant of rodent adaptive thermogenesis, The ß3-adrenoceptor was found to be down-regulated in obese fa/fa Zucker rat BAT and WAT (8) and in obese ob/ob mouse adipose tissues compa red to lean animals (10).…”

Section: The ßTadrenoceptor -Ucp1 Ax/smentioning

confidence: 99%

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Old and new determinants in the regulation of energy expenditure

Russell¹,

Giacobino²

2002

J Endocrinol Invest

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ABSTRACT. Bw gain is controlled by energy intake on one hand and expenditure on the other. The components of energy expenditure are basal metabolism, exercise induced thermogenesis and adaptive UNCOUPLING PROTE/N-1 (UCP1)In rodents, brown adipose tissue (BAT) is an important site of adaptive thermogenesis. Cold exposure has for long been known to induce, via stimulation of the sympathetic nervous system, an increase in BAT thermogenesis referred to as adaptive cold-induced thermogenesis (CIT), (1). Furthermore, it has been observed that voluntary overeating induced in rats by the administration of a palatable, so-called "cafeteria" diet also induced an increase in BAT thermogenesis which was called adaptive diet-induced thermogenesis (OIT) (2).The main producer of heat in BAT is the uncoupling protein-1 (UCP1). This mitochondria inner membrane protein uncouples oxidative phosphorylation by dissipating the proton gradient generated by the re-oxidation of NAOH H+ in the respiratory chain. The UCP1-mediated proton transport requires the presence of fatty acids and is specificalIy inhibited by purine di-and triphosphate nucleotides (3). The consequence of UCP1 activity is a decrease in the amount of ATP formed by the ATP synthase and energy dissipation as heat. UCP1 knockout mice were generated and they were unable to maintain their body temperature upon cold exposure but did not become obese (4).These data confirmed the importance of UCP1 in Key-words: ßTadrenoceptor. uncoupling CIT and suggested that, in UCP1 knockout mice, alternative mechanisms for maintaining body mass wh ich could not protect against the cold were turned on, In humans, BAT is present in newborn babies and decreases in 4-6 months after birth (5, 6). It is therefore generally believed that there is no UCP1 in human adults. THE ßTADRENOCEPTOR -UCP1 AX/SThe family of the ß-adrenoceptors were considered to consist of ß1-and ß-rsubtypes until1989 when a third subtype was cloned (7). This third subtype called the ß3-adrenoceptor was found to be the predominant ß-subtype in rodent BAT and white adipose tissue (WAT) (8,9). When the BAT sympathetic nervous system activity is increased by cold exposure or overfeeding, the stimulatory effect on UCP1 activity and expression is therefore mediated essentially by the ß3-adrenoceptor (9). Therefore, the ß3-adrenoceptor-UCP1-axis is a major determinant of rodent adaptive thermogenesis, The ß3-adrenoceptor was found to be down-regulated in obese fa/fa Zucker rat BAT and WAT (8) and in obese ob/ob mouse adipose tissues compa red to lean animals (10). In ß3-adrenoceptor knockout mice, the capacity to adapt to a cold environment was fully preserved, but there was an increase in fat deposition under basal conditions and in response to a high fat diet (11). These data confirmed the importance of the ß3-adrenoceptor in OIT and suggested that, in the ß3-adrenoceptor knockout mice, alternative mechanisms for maintaining body temperature were turned on. In rodents, cold exposure was found to recruit mul- A.P. Russe 1...

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The Pharmacologic Approach to the Treatment of Obesity

Weiser

Frishman

Michaelson

et al. 1997

The Journal of Clinical Pharma

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Obesity is a major risk factor for morbidity and mortality, and a series of pharmacologic approaches are available for helping to manage the problem. Obesity is caused by an imbalance between caloric intake and energy expenditure, which is influenced by both environmental and genetic factors. Pharmacologic treatments include anorexigenic agents, which fall into two broad categories: those that act via brain catecholamine pathways and those that act via serotonin pathways. The most recent oral agents approved are dexfenfluramine, which is currently being marketed, and sibutramine. Both agents inhibit the control reuptake of serotonin but in addition may have effects on thermogenesis. Under investigation are agents that increase energy expenditure: the beta 3-adrenergic receptor agonists and drugs that prevent the intestinal absorption of free fatty acids and cholesterol. In development are innovative approaches to influence leptin and its receptors, various obesity genes, and biologic substances thought to influence satiety (neuropeptide Y, enterostatin, cholecystokinin, bombesin, and amylin). Obesity has now become a major target for drug development not only for affecting obesity per se but also for managing and preventing comorbid conditions such as diabetes and cardiovascular disease.

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μ3-Adrenoceptor: an update

Cited by 105 publications

References 0 publications

Analysis of Candidate Genes for Insulin Resistance in Essential Hypertension

Analysis of Candidate Genes for Insulin Resistance in Essential Hypertension

Old and new determinants in the regulation of energy expenditure

The Pharmacologic Approach to the Treatment of Obesity

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