Context. Recently, we showed that drinking 500 ml water induces thermogenesis in normal-weight men and women.

Objective. We now repeated these studies in a randomized, controlled, crossover trial in overweight or obese, otherwise healthy subjects (8 men and 8 women) comparing also the effects of 500 ml iso-osmotic saline or 50 ml water.

Results. Only 500 ml water increased energy expenditure by 24% over the course of 60 minutes after ingestion, while iso-osmotic saline and 50 ml water had no effect. Heart rate and blood pressure did not change in these young, healthy subjects.

Conclusions. Our data exclude volume-related effects or gastric distension as the mediator of the thermogenic response to water drinking. Instead, we hypothesize the existence of a portal osmoreceptor, most likely an ion channel.