On the other hand the results from placebo controlled studies, conducted in different clinical settings and in several countries, were highly consistent that EC is an effective and well tolerated anti-obesity therapy. Several reasons may justify this discrepancy. First, our is the only study conducted in patients with very high grade obesity addressed to bariatric surgery. Accordingly, one month may be a too short treatment period to obtain relevant anti-obesity results, particularly in patients with a massive obesity characterized by high sympathetic activity. In addition, our study was performed in a small sample of patients, and this might have limited the chance to observe the drug efficiency. The reported increase of RMR after EC treatment may be due to different physiological mechanisms, including an increased energy expenditure through thermogenesis of brown adipose tissue and skeletal muscle. At present, the recruitment in BAT is considered of great interest. This is because BAT is now considered an active tissue even in adult humans, with the capacity to oppose obesity or its development by burning some of the energy we consume by feeding. In particular, human BAT depots would be constituted mainly of beige/brite adipocytes, expressing UCP1 when physiologically stimulated by cold or drugs. Thus increasing proliferation and activation of these fat cells might play a relevant role in obesity treatment. However, a more appropriate reevaluation of these findings suggest that the relative contribution of the beige/brite adipose tissue to the total thermogenesis capacity, at least in animals, would be marginal. We focused our attention to the putative thermogesis activity of skeletal muscle by investigating UCP3 expression in morbidly obese females. We found no changes in UCP3S and UCP3L isoform mRNAs in rectus abdominis of obese treated with EC in comparison to obese patients treated with placebo. These results would suggest that muscle UCP3 is not directly linked to the increased RMR induced by EC in obese subjects. A relevant limitation of our study is that we could measure muscle UCP3 expression only as mRNA, but not as protein. Rephrasing the title of a thoughtful review article by Nedergaard and Cannon ‘‘UCP3 mRNA does not produce heat’’.