Peripherally administered baclofen reduced food intake and body weight in db/db as well as diet-induced obese mice.
Peripheral administration of baclofen significantly reduced food intake and body weight increase in both diabetic (db/db) and diet-induced obese mice for 5 weeks, whereas it had no significant effects on energy balance in their lean control mice. Despite the decreased body weight, neuropeptide Y expression in the arcuate nucleus was significantly decreased, whereas pro-opiomelanocortin expression was significantly increased by baclofen treatment. These data demonstrate that the inhibitory effects of baclofen on body weight in the obese mice were mediated via the arcuate nucleus at least partially, and suggest that GABA(B) agonists could be a new therapeutic reagent for obesity.
Sato
Ikuko
I
Department of Endocrinology and Diabetes, Field of Internal Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Arima
Hiroshi
H
Ozaki
Noriyuki
N
Ozaki
Nobuaki
N
Watanabe
Minemori
M
Goto
Motomitsu
M
Shimizu
Hiroshi
H
Hayashi
Masayuki
M
Banno
Ryouichi
R
Nagasaki
Hiroshi
H
Oiso
Yutaka
Y
D054392:Adipokines / Q000097:blood; D052436:Adipose Tissue, White / Q000187:drug effects / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D001418:Baclofen / Q000008:administration & dosage / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D004032:Diet; D004435:Eating / Q000187:drug effects*; D018755:GABA Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D058786:GABA-B Receptor Agonists; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015431:Weight Loss
D054392:Adipokines; D019440:Anti-Obesity Agents; D001786:Blood Glucose; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D009478:Neuropeptide Y; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D001418:Baclofen