Peripheral serotonin enhances lipid metabolism by accelerating bile acid turnover.
Serotonin is synthesized by two distinct tryptophan hydroxylases, one in the brain and one in the periphery. The latter is known to be unable to cross the blood-brain barrier. These two serotonin systems have apparently independent functions, although the functions of peripheral serotonin have yet to be fully elucidated. In this study, we have investigated the physiological effect of peripheral serotonin on the concentrations of metabolites in the circulation and in the liver. After fasting, mice were ip injected with 1 mg serotonin. The plasma glucose concentration was significantly elevated between 60 and 270 min after the injection. In contrast, plasma triglyceride, cholesterol, and nonesterified fatty acid concentrations were decreased. The hepatic glycogen synthesis and concentrations were significantly higher at 240 min. At the same time, the hepatic triglyceride content was significantly lower than the basal levels noted before the serotonin injection, whereas the hepatic cholesterol content was significantly higher by 60 min after the injection. Furthermore, serotonin stimulated the contraction of the gallbladder and the excretion of bile. After the serotonin injection, there was a significant induction of apical sodium-dependent bile acid transporter expression, resulting in a decrease in the concentration of bile acids in the feces. Additionally, data are presented to show that the functions of serotonin are mediated through diverse serotonin receptor subtypes. These data indicate that peripheral serotonin accelerates the metabolism of lipid by increasing the concentration of bile acids in circulation.
Watanabe
Hitoshi
H
Cellular Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
Akasaka
Daisuke
D
Ogasawara
Hideki
H
Sato
Kan
K
Miyake
Masato
M
Saito
Kazuki
K
Takahashi
Yu
Y
Kanaya
Takashi
T
Takakura
Ikuro
I
Hondo
Tetsuya
T
Chao
Guozheng
G
Rose
Michael T
MT
Ohwada
Shyuichi
S
Watanabe
Kouichi
K
Yamaguchi
Takahiro
T
Aso
Hisashi
H
D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000097:blood / Q000378:metabolism; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000097:blood / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012701:Serotonin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*
D001647:Bile Acids and Salts; D007328:Insulin; D012701:Serotonin; D006003:Glycogen; D005947:Glucose