This review discusses regulation of body weight through brain circuits that use a variety of neuropeptides and transmitters, and that are responsive to endocrine and metabolic signals. Novel pharmaceutical drugs which target these pathways are reviewed as possible additions to lifestyle interventions for the treatment of obesity.

The ideal weight-loss drug should reduce energy intake and/or increase energy expenditure without adverse side effects. Most energy expenditure is due to the basal metabolic rate, and does not fluctuate extensively during the day, except when performing physical exercise. By contrast, energy intake is highly variable during the day. Thus, drugs that target energy intake are considered to act on the more dynamic part of the energy balance equation.

The modes of action of new anti-obesity drugs are reviewed and contrasted with previous drugs which were removed from clinical use because of unacceptable psychiatric and cardiovascular side effects. This review also notes the large variability in drug response, which may originate from individual differences in the cause of obesity and the difficulty in sustaining lifestyle changes. For the treatment of obesity, the review concludes that a personalized medicine approach for drugs in combination with lifestyle advice is expected to be more successful than one treatment for all.

Adan RA: Mechanisms underlying current and future anti-obesity drugs. Trends Neuroscience [Epub ahead of print, Jan. 8, 2013; doi: 10.1016/j.tins.2012.12.001].

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