The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: Comparison to sibutramine and rimonabant
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The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: Comparison to sibutramine and rimonabant. / Hansen, Henrik H; Hansen, Gitte; Tang-Christensen, Mads; Larsen, Philip J; Axel, Anne Marie Dixen; Raben, Anne; Mikkelsen, Jens D.
In: European Journal of Pharmacology, Vol. 636, 10.04.2010, p. 88-95.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: Comparison to sibutramine and rimonabant
AU - Hansen, Henrik H
AU - Hansen, Gitte
AU - Tang-Christensen, Mads
AU - Larsen, Philip J
AU - Axel, Anne Marie Dixen
AU - Raben, Anne
AU - Mikkelsen, Jens D
PY - 2010/4/10
Y1 - 2010/4/10
N2 - Tesofensine, a novel triple monoamine reuptake inhibitor, produces a significant weight loss in humans. The present study aimed at characterizing the weight-reducing effects of tesofensine in a rat model of dietinduced obesity. Sibutramine and rimonabant were used as reference comparators. Compared to baseline, long-term treatment with tesofensine (28 days, 1.0 or 2.5 mg/kg, p.o.) resulted in a significant, dosedependent and sustained weight loss of 5.7 and 9.9%, respectively. Sibutramine (7.5 mg/kg, p.o.) treatment caused a sustained weight loss of 7.6%, whereas the employed dose of rimonabant (10 mg/kg, p.o.) only produced a transient weight reduction. While all compounds exhibited a significant inhibitory effect on food intake which gradually wore off, the hypophagic effect of tesofensine was longer lasting than sibutramine and rimonabant. In contrast to tesofensine, the body weight of pair-fed rats returned to baseline at the end of the study, which may indicate that tesofensine stimulated energy expenditure. The differential efficacy on weight reduction was also reflected in lowered body fat depots, as tesofensine and sibutramine most efficiently reduced abdominal and subcutaneous fat mass which was paralleled by reduced plasma lipid levels. In an oral glucose tolerance test, only tesofensine significantly suppressed the plasma insulin response below the level that could be obtained by paired feeding, indicating that tesofensine further improved glycemic control. In conclusion, the robust weight loss with long-term tesofensine treatment is likely due to a combined synergistic effect of appetite suppression and increased energy expenditure.
AB - Tesofensine, a novel triple monoamine reuptake inhibitor, produces a significant weight loss in humans. The present study aimed at characterizing the weight-reducing effects of tesofensine in a rat model of dietinduced obesity. Sibutramine and rimonabant were used as reference comparators. Compared to baseline, long-term treatment with tesofensine (28 days, 1.0 or 2.5 mg/kg, p.o.) resulted in a significant, dosedependent and sustained weight loss of 5.7 and 9.9%, respectively. Sibutramine (7.5 mg/kg, p.o.) treatment caused a sustained weight loss of 7.6%, whereas the employed dose of rimonabant (10 mg/kg, p.o.) only produced a transient weight reduction. While all compounds exhibited a significant inhibitory effect on food intake which gradually wore off, the hypophagic effect of tesofensine was longer lasting than sibutramine and rimonabant. In contrast to tesofensine, the body weight of pair-fed rats returned to baseline at the end of the study, which may indicate that tesofensine stimulated energy expenditure. The differential efficacy on weight reduction was also reflected in lowered body fat depots, as tesofensine and sibutramine most efficiently reduced abdominal and subcutaneous fat mass which was paralleled by reduced plasma lipid levels. In an oral glucose tolerance test, only tesofensine significantly suppressed the plasma insulin response below the level that could be obtained by paired feeding, indicating that tesofensine further improved glycemic control. In conclusion, the robust weight loss with long-term tesofensine treatment is likely due to a combined synergistic effect of appetite suppression and increased energy expenditure.
M3 - Journal article
VL - 636
SP - 88
EP - 95
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
ER -
ID: 46431937