The alpha/beta-adrenergic receptor blocker arotinolol activates the thermogenesis of brown adipose tissue in monosodium-L-glutamate-induced obese mice.
We have found previously that arotinolol, an alpha/beta-adrenergic blocker, increases blood flow in brown adipose tissue (BAT) in a similar extent as BRL 26830A, a beta 3-adrenoceptor agonist. We tested the hypothesis that arotinolol activates thermogenesis in BAT, leading to weight loss in monosodium-L-glutamate-induced (MSG-induced) obese mice and saline-treated controls. Six weeks of standard animal feed (CE-2) containing arotinolol hydrochloride (350 mg/kg CE-2), which reduced mean blood pressure in MSG-treated mice, significantly increased the mitochondrial protein content in BAT, and activated the specific and total binding of guanosine-5'-diphosphate (GDP) in BAT mitochondria, leading to a reduction of obesity in both MSG- and saline-treated mice vs. the control groups fed with CE-2 diet alone. However, six weeks of CE-2 diet containing propranolol hydrochloride (525 mg/kg CE-2) a non-selective beta-blocker, markedly reduced the specific and total binding of GDP in BAT mitochondria, leading to weight gain in both MSG- and saline-treated mice. These findings support the hypothesis, that arotinolol activates BAT thermogenesis, leading to weight loss.
Yoshida
T
T
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Sakane
N
N
Wakabayashi
Y
Y
Yoshioka
K
K
Umekawa
T
T
Kondo
M
M
D000273:Adipose Tissue / Q000187:drug effects; D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000032:analysis; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000201:enzymology; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use; D012970:Sodium Glutamate
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C024523:arotinolol; D011433:Propranolol; D003576:Electron Transport Complex IV; D012970:Sodium Glutamate