Background: 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. Objective: 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. Design: 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. Results: Despite efforts to keep body weight and composition constant, TE induced a 1.8 kg weight loss above PL after 2 weeks' treatment (Po0.0001). 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%; Po0.05) when adjusted for changes in body composition. Furthermore, TE increased 24-h fat oxidation as compared with PL (18 g; Po0.001). Conclusion: TE has a pronounced effect on appetite sensations and a slight effect on energy expenditure at nightFboth effects can contribute to the strong weight-reducing effect of TE.

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Cow's milk products have a central role in treatment of under nutrition, and the introduction of products with a high milk content (F-100 and ready to use therapeutic foods) has resulted in marked improvements in weight gain and reduction in mortality. Milk also has a specific effect on linear growth. Milk protein has a high quality score (PDCAAS) and contains many peptides and other bioactive factors, which might have special effects on recovery from under nutrition. Milk is an important source of minerals supporting growth (type II nutrients), such as potassium, magnesium, phosphorus and zinc, and the high lactose content also seems to support growth due to a prebiotic effect and improved absorption of minerals. The risk that the use of cow's milk products suppresses breastfeeding should be prevented by supporting mothers in breastfeeding. There is consensus that children with severe under nutrition should be treated with products with high milk content, but because of the high cost of milk there is a need to perform more studies to determine the minimal amount of milk protein needed to make a clinically relevant difference in treating the 36 million children with moderate wasting. Such studies should not only focus on weight gain but also on linear growth, body composition, physical activity and cognitive development.