Fat News: A Novel ActRIIB Decoy Receptor in the BAT-tle for Obesity

Abstract

The most straightforward solution to fight overweight and obesity seems to be condensed in the simple formula: eat less, do more exercise! Although this traditional recipe has proven its general validity for many decades, the prevalence for adiposity and obesity steadily increased in past decades and in 2008 approximately 1.5 billion adults were overweight, of which one-third were classified to be obese (1). Considering the World Health Organization statistics, one has to admit that this simple weight-loss formula does not work efficiently in industrialized societies. Explanations why these apparently easy-to-use obesity prevention guidelines are failing remain complex. Among others, and in the absence of medical disorders leading to overweight, the easy availability of energydense, highly palatable and digestible foods, socioeconomic aspects, and the desire for comfort in modern societies certainly play a decisive role in explaining why the clothing industry keeps adding X in front of the L. Down-to-earth, obesity is a consequence of an imbalance between the two processes energy intake and energy expenditure (EE). Various success and failure stories of reducing energy intake by dietary approaches (2), bariatric interventions (3, 4), and pharmacological inhibition of appetite and nutrient absorption (5–7) have been reported. However, this editorial focuses on the EE side of the equation and features a study from Koncarevic et al. (8) who targeted EE of mice by pharmacological stimulation of muscle growth and browning of white adipose tissue (WAT). Apparently, the easiest way to increase EE is by increasing physical activity. However, consumption-oriented lifestyle and tightened occupational conditions do not always allow us to fully compensate energy intake with physical activity. Another option to increase EE has originally been suggested by Rothwell and Stock (9) more than 30 yr ago. At that time, the authors observed that rats that were fed ad libitum an energy-dense diet displayed hyperphagia but gained less weight than was expected from the energy content of the ingested food. Therefore, it was suggested that burning off excess calories by diet-induced thermogenesis in brown adipose tissue (BAT) could be a physiological mechanism to protect from obesity (9). Interestingly, low-carbohydrate, high-fat diets, the most popular one being the Atkins diet, claim to lead to body weight loss independent of energy intake but by increasing EE and by dispensing energy via diet-induced loss of ketone bodies (10). In fact, dietary trials in overweight subjects (11) as well as experiments in rats (12) found this type of diet to be efficient for induction of body weight loss. However, the theory behind weight loss with these diets was criticized soon after its publication (13, 14), and in rats, it has recently been shown that low-carbohydrate, high-fat diets do not trigger increased EE. In contrast, it was reported that isoenergetic consumption of this type of diet leads to lower EE and to a massive accumulation of visceral fat when compared with rats fed a control diet (12, 15). Early studies in hibernating mammals led to the discovery that BAT is a metabolically highly active tissue with the unique feature of dissipating chemical energy into thermal energy (heat) needed to defend body core temperature in cold environments (16, 17). The recent discovery that adult humans also possess considerable amounts of metabolically active BAT has instantly renewed the attention to this long unappreciated tissue (18, 19). The idea that external stimuli could be used to increase BAT activity or