Noninvasive treatments like environmental stimulation are able to increase response to leptin and induce BDNF expression in the brain. Emerging evidences point to the antidepressant selective serotonin reuptake inhibitor Fluoxetine FLX as a drug with effects similar to environmental stimulation. FLX is known to impact on body weight, with mechanisms yet to be elucidated. Wild type obese mice treated with FLX showed reduced weight gain, increased energy output, and differently from untreated obese mice, a preserved acute response to leptin in terms of activation of the intracellular leptin transducer STAT3. In conclusion, FLX impacts on energy balance and induces leptin sensitivity and an intact TrkB function is required for these effects to take place. The hormone leptin, secreted by the white adipose tissue WAT, plays a key role in the complex interplay between peripheral organs and the brain to regulate body weight 1, by informing the brain about the status of long-term energy stores, in order to repress food intake and promote energy expenditure 2. The former is activated by leptin and induces an anorectic response 6, whereas the latter, inhibited by leptin, stimulates feeding 7. The above depicted scenario is how the system should work to regulate energy balance and prevent excessive weight accumulation. However, obese people display high levels of leptin and therapy with the recombinant hormone has proved largely ineffective to treat obesity 8, leading to hypothesize the existence of a set-point for leptin responsiveness, which is programmed via an interaction between genetic background and environment 9. Obesity can be interpreted as an upwards shift of the set point, resulting in a positive energy balance that ultimately leads to fat stores increased deposition. Modulating leptin sensitivity, rather than leptin levels, is then an emerging frontier for obesity therapy and prevention.
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In this mouse BDNF signaling is effectively blunted by administration of the commercially available compound 1NaPP1 33, a drug able to cross the blood brain barrier FLX is known to impact on body weight, with mechanisms yet to be elucidated. Medically reviewed by Daniel Bubnis, M.
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