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Secretin Links Brown Fat to Food Intake: New Perspectives for Targeting Energy Balance in Humans

In 1902, Neumann referred to the concept of Luxuskonsumption in his habilitation thesis, essentially stating that we can dissipate excess nutritional energy as heat to keep slim: “On the other hand, we also know very well that someone who otherwise ‘lives well’ consumes a sufficient amount of food and in the process enters into a luxury consumption in the organism” (1)*. Sixty years later, the thermogenic function of brown fat was first recognized, leading to significant research efforts to address the role of the sympathetic nervous system for coldand diet-induced thermogenesis in brown fat. Recruitment and activation of brown fat thermogenesis was envisioned as a feasible strategy to promote negative energy balance and lose weight. In retrospect, research targeting brown fat for obesity therapy has been characterized by phases of skepticism and enthusiasm, with the latter currently prevailing (2). To date, however, it remains unclear whether sufficient brown fat capacity for energy expenditure can be recruited in people with obesity to reduce body weight effectively (3). In the positive case, this would require that increased brown fat thermogenesis is not fully compensated by increasing food intake (4). Ten years ago, landmark publications reported on the presence of cold-inducible brown fat in human adults (5). Cold-inducible activation of human brown fat is impaired with age and in people with obesity and type 2 diabetes, whereas cold acclimation initiates remission in association with improved metabolic homeostasis. In principle, given the current estimate of more than 300 g, total brown fat mass in humans could significantly promote negative energy balance if permanently active (6). Our lifestyle in thermoneutral environments, however, normally precludes cold-induced brown fat activation.