The discovery of new types of adipose cells, new adipokines and new biological functions of tissues containing these cells could provide many new potential therapies for the treatment of obesity, diabetes and related disorders. The list of targets that may induce browning or activate beige/brown adipose tissue is expanding daily, and research in the coming years will reveal which of these are robust enough to represent new opportunities for human therapy. Several key questions arise: first, is it more important to create new brown or beige fat cells or to activate existing one in an individual, or do we need to do both? Second, many studies in rodents have revealed beneficial effects on glucose homeostasis and diabetes, which may not be in proportions with effects on body weight per se. Are there important effects of brown/beige fat that are not strictly tied to effects on overall adiposity? It might be foolish to place all our hope on novel pharmacological treatment. It will remain very important that public health initiatives stress the health dangers of physical inactivity and overeating; the coming years will also reveal whether a lack of time outside the thermoneutral zone should be considered an additional danger to health. Based on the results to date, it can be hypothesised that regular exposure to mild cold may become—together with exercise and weight loss—a third lifestyle factor that can be used to stimulate health . As with lifestyle and exercise, we need to understand how much cold is enough; are we facing a ‘30 min of cold per day keeps the doctor away’ advice, or will 30 min of cold per day not be sufficient to counterbalance being in the thermoneutral zone for 23.5 h per day, analogous to 30 min of exercise per day perhaps not being sufficient to counterbalance 23.5 h of sedentariness? The cold acclimatisation tests carried out to date have lasted 2–6 h/day for 10 days to 6 weeks, with temperatures varying from very cold (10°C with shivering) to mild cold (19°C). Even mild cold (without shivering) increases BAT activity, whole body energy metabolism and decreases body fat, but long-term effects on measures of health still need to be established, and optimal exposure times, i.e. a compromise between realistic and effective, will need to be figured out. Furthermore, it needs to be established whether the potential beneficial effects of cold are only due to the activation of BAT, or also involve other tissues with a thermogenic potential, such as skeletal muscle. Cooling protocols would need to be developed taking into account the large variability in individual and group-specific responses with respect to effects on BAT and energy metabolism and in terms of acceptability, i. e. thermal comfort. These group-specific responses also apply to potential side effects, as, for example, the elderly may not respond adequately to prolonged mild cold and their blood pressure may rise to unhealthy levels.
An interesting aspect of cold ‘therapy’ is that it can be incorporated into our daily environment, i.e. the indoor environment. Because most people are exposed to indoor conditions for more than 90% of their time, health aspects of ambient temperatures warrant exploration. What would it mean if we were to let our bodies, rather than the central heating, control body temperature? Even if the effect at an individual level is small, with widespread application in dwellings and offices, the effect on the population could be significant. In the built environment the temperature is controlled to satisfy thermal comfort for the average (male) person. This is according to the predicted mean vote model that is generally applied worldwide. This results in relatively high temperatures in wintertime. By lack of exposure to a varied ambient temperature, entire populations may be prone to developing diseases such as obesity and in the same time may become more vulnerable to sudden temperature changes during cold waves. Nowadays the so-called adaptive comfort model is more widely applied. This model recognises that humans tolerate and adapt to different thermal environmental conditions depending on outdoor environmental conditions. For the next 50 years, we envision that indoor temperature will be used to enhance metabolism and resilience, and thereby health in general. Although scientific attention is now focused on cold, the health aspects of mild heat are still an enigma and need to be explored. Therefore the next 50 years will unravel whether, from a health perspective, indoor temperatures should follow outdoor temperature variation at acceptable but healthy levels, both daily and seasonally.