Anti-Obesity Effects of Selective Agonists to the .BETA.3-Adrenergic Receptor in Dogs. II. Recruitment of Thermogenic Brown Adipocytes and Reduction of Adiposity after Chronic Treatment with a .BETA.3-Adrenergic Agonist.

Sasaki, Noriyuki; Uchida, Eiji; Niiyama, Masayoshi; Yoshida, Toshihide; Saito, Masayuki

doi:10.1292/jvms.60.465

Cited by 30 publications

(17 citation statements)

References 23 publications

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“…These results, together with our previous findings of the CL-induced expression of UCP1 in the adipose tissues [17,20,25], suggest that antiobesity effect of β3-AR agonists is attributable to increased thermogenesis not only by UCP1 but also by UCP2 and UCP3.…”

Section: Discussionsupporting

confidence: 82%

.BETA.3-Adrenergic Agonist Up-Regulates Uncoupling Proteins 2 and 3 in Skeletal Muscle of the Mouse.

Nakamura

Nagase

Asano

et al. 2001

The Journal of Veterinary Medical Science

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ABSTRACT. Chronic stimulation of the β3-adrenergic receptor (AR) in obese animals resulted in a reduced adiposity associated with an increased expression of thermogenic uncoupling protein (UCP)1 in adipose tissues. In this study, the mRNA expression of newly cloned UCP isoforms (UCP2 and UCP3) were examined in obese yellow KK and C57BL control mice. UCP2 mRNA was found in all tissues examined, with higher levels in adipose tissues and skeletal muscle of the obese mice. UCP3 mRNA was expressed in skeletal muscle, heart and brown adipose tissue similarly in the two mouse strains. Daily injection of a selective β3-adrenergic agonist, CL316,243 (0.1 mg/kg), for 10 days resulted in a marked reduction of white fat pad weight and 1.8~4.8-fold increase in the mRNA levels of UCP2 and UCP3 in skeletal muscle of obese mice. No noticeable change in the UCP2 and 3 mRNA levels was found in brown and white adipose tissues. It was also found that CL316,243 injection produced a marked and sustained elevation of the plasma free fatty acid level. These results, together with our previous findings of the fatty acid-induced UCP expression in a myocyte cell line in vitro, suggest that the β3-AR agonist-induced UCP expression in skeletal muscle may be mediated through the elevated plasma free fatty acids. It was also suggested that anti-obesity effect of β3-AR agonists is attributable to increased thermogenesis not only by UCP1 but also by UCP2 and UCP3.KEY WORDS: adipose tissue, β3-adrenergic agonist, fatty acid, obese mouse, uncoupling protein.

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Section: Discussionsupporting

confidence: 82%

.BETA.3-Adrenergic Agonist Up-Regulates Uncoupling Proteins 2 and 3 in Skeletal Muscle of the Mouse.

Nakamura

Nagase

Asano

et al. 2001

The Journal of Veterinary Medical Science

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“…These results suggest that phenylethanolamines are more effective agonists to β3-AR, at least in the dog, and may be more useful as anti-obesity drugs. The anti-obesity effect of CL316,243 will be reported in the following paper [19].…”

Section: Discussionmentioning

confidence: 92%

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.

et al. 1998

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ABSTRACT. It is known that in rodents and humans the β3-adrenergic receptor (β3-AR) is present primarily in adipocytes and plays a significant role in the adrenergic stimulation of lipolysis. We examined the expression of β3-AR mRNA in the dog and the lipomobilizing effects of β3-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%) β3-AR cDNA. The β3-AR mRNA was present at high levels in subcutaneous and visceral adipose tissues, but undetectable in other organs. When a selective β3-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 β3-AR agonist, also showed a similar lipomobilizing effect, but with lower potency. β3-AR agonist infusion also increased the plasma insulin level. These results suggested that functional β3-AR is present in adipose tissues of the dog and that it is effective for in vivo lipomobilization. -KEY WORDS: adipose tissue, adrenergic agonist, β3-adrenergic receptor, canine, lipomobilization.J. Vet. Med. Sci. 60(4): 459-463, 1998 tolerance, and reduces adiposity [17,20]. Similar antiobesity and anti-diabetic effects of β3-AR agonists were also reported in other obese mouse and rat models [1,4,10]. In veterinary practice for companion animals, obesity is the most common nutritional disorder, as in humans [5,15]. However, in contrast to rodents and humans, there have been few reports about β3-AR and effects of its agonists in the canine and feline. As a series of experiments for possible application of β3-AR agonists to the pharmacological treatment of companion animal obesity, in this study, we confirmed the presence of canine β3-AR by analysis of its cDNA, and examined the acute lipomobilizing effects of two selective β3-AR agonists in non-obese healthy dogs. MATERIALS AND METHODS Animals:One male and six female adult beagle dogs weighing 10-13 kg were used several times each under various experimental conditions. Each experiment was carried out at least 7 days after the last one. The animal care and procedures were in accordance with the guidelines of the Animal Care and Use Committee of Hokkaido University. In mammals, there are two types of adipose tissues, white and brown adipose tissues. Although both tissues consist of a large number of adipocytes accumulating triglycerides, their physiological roles contrast: that is, white adipose tissue is the major site of energy storage and releases fatty acids into blood, while brown adipose tissue oxidizes fatty acids to produce heat and is the site of energy expenditure. Hydrolysis of triglycerides in adipocytes is largely dependent on the β-adrenergic action of catecholamines. Pharmacological and biochemical studies have demonstrated that three isoforms of the β-adrenergic receptor (AR), β1-, β...

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“…The ADRB3 agonist might lead to an increase in energy expenditure and decrease in deposit of fat in adipose tissues of humans (Larsen et al, 2002), dogs (Sasaki et al, 1998b) and rodents (Weyer et al, 1999). The effects of ADRB3 agonists held interest in human medicine for the treatment of obesity and type 2 diabetes, but it was disappointing in clinical studies Larsen et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Distribution and quantification of β-3 adrenergic receptor in tissues of sheep

Liu

et al. 2011

Animal

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The b-3 adrenergic receptor (ADRB3) is a G-protein coupled receptor involved in regulating lipolysis, as part of homeostatic regulation. In this study, South African Mutton Merino and Shanxi Dam Line were used to study the distribution and quantification of ADRB3 in adipose (subcutaneous, omental, retroperitoneal, mesenteric and perirenal fat) and non-adipose (heart, liver, spleen, lung and kidney) tissues of sheep. The protein was determined by immunohistochemical technique and by mRNA abundance via real-time polymerase chain reaction. ADRB3 was detected in all studied tissues with abundance in adipose tissues higher than in non-adipose tissues ( P , 0.001). For adipose tissues, greater expression was found in deep deposits such as great omental and retroperitoneal fat than in subcutaneous fat ( P , 0.05). Significant differences ( P , 0.05) both for mRNA and for protein expression also existed between the two sheep flocks. These findings are consistent with the known function of ADRB3 in mediating lipolysis and homeostasis in adipose tissues.Keywords: b-3 adrenergic receptor, sheep, tissues, mRNA expression, immunohistochemistry ImplicationsIn this study, the b-3 adrenergic receptor (ADRB3) expression in various tissues of sheep was detected by immunohistochemical technique and by mRNA abundance via real-time PCR. Despite its low expression, the presence of ADRB3 in the spleen and kidney was found in livestock for the first time. Generally, ADRB3 expressed higher in adipose than in non-adipose tissues, and for the former, it was higher in deep fat deposits than in subcutaneous fat. The distributions are consistent with the known functions of ADRB3 in mediating lipolysis and homeostasis in adipose tissues, and relaxation of vascular smooth muscle in the cardiovascular system. The relation between low expression and its function in some viscera, for example, lung, spleen and kidney of sheep deserves further study.Introduction b-Adrenergic receptors (ADRBs) are G-protein coupled receptors that mediate effects of the endogenous catecholamines adrenaline and noradrenaline. Three subtypes of ADRBs have been identified, named ADRB1, ADRB2 and ADRB3, respectively. These receptors are present in most mammalian tissues, but the distribution of each subtype varies among tissues in a given species. Among the various physiological roles of ADRBs, the ADRB3 subtype mediates lipolysis and stimulates thermogenesis in adipose tissues (Cannon and Nedergaard, 2004) by activating uncoupling protein in mitochondria.In early studies, ADRB3 was identified mainly on the surface of white and brown adipocytes as reviewed by Strosberg (1997). In recent years, expression of the protein was also found in the human heart (Rozec and Gauthier , (Rodriguez et al., 1995).It has been confirmed that the mRNA of the ADRB3 gene is expressed in various tissues of domestic animals. The 2.0 kb ADRB3 transcript in the bovine brown adipose tissue (PietriRouxel et al., 1995), and two transcripts of 2.2 and 1.9 kb in porcine subcutaneous fat (McNeel and ...

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Anti-Obesity Effects of Selective Agonists to the .BETA.3-Adrenergic Receptor in Dogs. II. Recruitment of Thermogenic Brown Adipocytes and Reduction of Adiposity after Chronic Treatment with a .BETA.3-Adrenergic Agonist.

Cited by 30 publications

References 23 publications

.BETA.3-Adrenergic Agonist Up-Regulates Uncoupling Proteins 2 and 3 in Skeletal Muscle of the Mouse.

.BETA.3-Adrenergic Agonist Up-Regulates Uncoupling Proteins 2 and 3 in Skeletal Muscle of the Mouse.

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.

Distribution and quantification of β-3 adrenergic receptor in tissues of sheep

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