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.

Abstract

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...

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

“…A similar result was found in the lungs of pigs (McNeel and Mersmann, 1999). However, earlier studies have testified to the absence of mRNA expression in the lung and kidney of humans (Krief et al, 1993), rats (Evans et al, 1996) and dogs (Sasaki et al, 1998a). No study has reported its distribution and expression in the spleen to our knowledge.…”

“…The distribution in adipose tissues by the RT-PCR technique was reported also in other species, for example, in dogs (Sasaki et al, 1998a), in cattle (Sumner and McNamara, 2007) and in humans. Chamberlain et al (1999) andde Matteis et al (2002) demonstrated in humans (by immunohistochemistry) the existence of the ADRB3 protein in white adipocytes that came from subcutaneous fat and omental deposits.…”

“…However, earlier studies have suggested that there was an absence of ADRB3 in the liver of humans (Berkowitz et al, 1995), rats (Evans et al, 1996), dogs (Sasaki et al, 1998a) and pigs (McNeel and Mersmann, 1999). The slight difference may be attributed either to experimental techniques and/or species differences.…”

“…The mRNA expressed in the adipose tissue (Sumner and McNamara, 2007), mammary gland (Inderwies et al, 2003), gastrointestinal tracts including the cecum, ileum, colon and abomasum (Meylan et al, 2004;Kobel et al, 2006) and in the liver (Carron et al, 2005) of cattle through real-time polymerase chain reaction (RT-PCR) or ligand binding assay. The ADRB3 mRNA was also present in -E-mail: tglwzyc@yahoo.com.cn subcutaneous fat and visceral adipose tissues in dogs (Sasaki et al, 1998a) and in the ventricle and lungs in pigs (McNeel and Mersmann, 1999).…”

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

“…UCP2 and UCP3 expression in skeletal muscle have been reported to increase in response to fasting [1,8] , which is a representative cue to elevate plasma free fatty acids. The present results showed that administration of CL produced a sustained elevation of plasma free fatty acids as a result of their potent lipomobilizing action on adipose tissues [19,24]. Moreover, Weigle et al [23] demonstrated that elevation of circulating free fatty acid levels induced by Intralipid plus heparin infusion mimicked the increased expression of muscle UCP3 seen after fasting.…”