Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark.
Int J Obes (Lond). 2010 Nov;34(11):1634-43. doi: 10.1038/ijo.2010.87. Epub 2010 May 18.
Tesofensine (TE) is a new drug producing twice the weight loss in obese individuals as seen with currently marketed drugs. It inhibits the presynaptic reuptake of the neurotransmitters noradrenaline, dopamine and serotonin, and is thought to enhance the neurotransmission of all three monoamines. The mechanisms by which it produces weight loss in humans are unresolved.
The aim of this study is to investigate the mechanism(s) behind weight reduction by measuring energy expenditure and appetite sensations in overweight and obese individuals.
Thirty-two healthy, overweight or moderately obese men were treated with 2.0 mg TE daily for 7 days followed by an additional 7 days with 1.0 mg TE daily or corresponding placebo (PL) in a randomized, controlled trial. They were instructed to maintain habitual food intake and physical activity throughout. Twenty-four-hour energy expenditure (24-h EE), fat oxidation and spontaneous physical activity were measured in a respiration chamber before and after treatment. Body composition was assessed by dual-energy X-ray absorption and appetite was evaluated by visual analogue scales in conjunction with a standardized dinner.
Despite efforts to keep body weight and composition constant, TE induced a 1.8 kg weight loss above PL after 2 weeks' treatment (P<0.0001). TE also induced higher ratings of satiety and fullness and concomitantly lower prospective food intake than placebo. No significant effect of TE on total 24-h EE could be demonstrated compared with PL, but higher energy expenditure was observed during the night period (4.6%; P<0.05) when adjusted for changes in body composition. Furthermore, TE increased 24-h fat oxidation as compared with PL (18 g; P<0.001).
TE has a pronounced effect on appetite sensations and a slight effect on energy expenditure at night-both effects can contribute to the strong weight-reducing effect of TE.
Tesofensine（TE）是一种新型药物，能使肥胖个体的体重减轻，效果是目前市售药物的两倍。它抑制神经递质去甲肾上腺素、多巴胺和 5-羟色胺的突触前再摄取，被认为能增强这三种单胺类递质的神经传递。其在人体内产生减肥效果的机制尚未明确。
本研究旨在通过测量超重和肥胖个体的能量消耗和食欲感觉，探讨其减肥的机制。
32 名健康、超重或中度肥胖的男性参与了这项随机、对照试验，他们每天接受 2.0mg TE 治疗 7 天，然后每天接受 1.0mg TE 或相应安慰剂（PL）治疗 7 天。他们被要求在整个试验期间保持习惯性的饮食摄入和身体活动。在治疗前后，他们在呼吸室中测量了 24 小时能量消耗（24-h EE）、脂肪氧化和自发身体活动。通过双能 X 射线吸收法评估身体成分，通过视觉模拟量表结合标准化晚餐评估食欲。
尽管努力保持体重和成分不变，TE 在 2 周治疗后使体重比 PL 增加 1.8kg（P<0.0001）。TE 还引起更高的饱腹感和满足感评分，同时比 PL 降低了预期的食物摄入量。与 PL 相比，TE 对总 24-h EE 没有显著影响，但调整身体成分变化后，夜间能量消耗增加了 4.6%（P<0.05）。此外，TE 增加了 24-h 脂肪氧化，与 PL 相比增加了 18g（P<0.001）。
TE 对食欲感觉有明显影响，对夜间能量消耗有轻微影响-这两种作用都有助于 TE 的强烈减肥效果。
