Treatment with the 5-HT3 antagonist tropisetron modulates glucose-induced obesity in mice.
OBJECTIVE
Sugar consumption has increased markedly over the last few decades and parallels the dramatic increase in overweight and obesity. Data obtained from animal studies suggest that the intestinal serotonergic system and herein particularly the serotonin receptor 3 (5-HT3R) may be involved in sugar detection and short-term control of food intake. Using a mouse model, we tested the hypothesis that blocking 5-HT3R prevents the development of sugar-induced obesity.


METHODS
For 8 weeks, C57BL/J6 mice were offered either water containing 30% glucose or plain water in addition to normal chow. The effect of oral treatment with the 5-HT3R antagonist, tropisetron (0.2 mg kg(-1) body weight), on body weight and caloric intake was studied.


RESULTS
Total caloric intake and weight gain were significantly increased in mice fed glucose compared with the control group. Tropisetron treatment reduced intestinal motility and almost completely blocked weight gain associated with glucose feeding; however, total caloric intake was not affected. The effect of tropisetron was not associated with a decreased expression of the intestinal and hepatic glucose transporters, SGLT1 (sodium-dependent glucose cotransporter) and Glut2 (glucose transporter 2); instead, the expression of these transporters was slightly increased by the 5-HT3R antagonist. However, expressions of carbohydrate responsive element binding protein and fatty acid synthase, as well as triglyceride levels in the liver were only enhanced in mice fed glucose, but remained unchanged at the level of the control group when mice were treated concomitantly with tropisetron. At the same time, beta-hydroxybutyrate dehydrogenase mRNA expression and plasma levels of ketone bodies were significantly increased.


CONCLUSIONS
Our results suggest that 5-HT3R is a new target for the modulation of hepatic glucose metabolism and for the prevention of obesity.
Weber
S
S
Department of Nutritional Medicine (180a), University of Hohenheim, Stuttgart, Germany.
Volynets
V
V
Kanuri
G
G
Bergheim
I
I
Bischoff
S C
SC
D000818:Animals; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D007211:Indoles / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D012702:Serotonin Antagonists / Q000008:administration & dosage*; D000077526:Tropisetron; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
D051246:Glucose Transport Proteins, Facilitative; D007211:Indoles; D012333:RNA, Messenger; D012702:Serotonin Antagonists; D000077526:Tropisetron; D005947:Glucose