Brite/beige adipocytes: a potential tool against obesity and diabetes?

Abstract

Energy balance is defined by two components: energy intake and energy expenditure. Even minor but chronic perturbations in either of these two components can lead to an increase (obesity) or decrease in body weight. Obesity is not only a significant problem in itself but is also a major inducer of type 2 diabetes, cardiovascular disease and certain forms of cancer. At present there is no satisfactory treatment for obesity and in reality little understanding of the cause of obesity, except for the self-evident statement that it arises from an imbalance between energy intake and energy expenditure. The presence of two distinct types of adipose tissue, which have opposing functions, has been known for decades. White adipose tissue (WAT) is the main tissue of energy storage, while brown adipose tissue (BAT) dissipates energy as heat and is required for non-shivering thermoregulation. Within classical white adipose tissue depots, a particular type of adipocytes sometimes occurs. These adipocytes manifest several classical brown adipocyte characteristics, most notably the presence of UCP1 (uncoupling protein-1) and through this the ability to dissipate energy, to burn away (extra) food and thus to counteract the development of obesity. The identification of a novel type of adipocytes, i.e. the brite/beige adipocytes, that possess the ability to increase energy expenditure and that are localized within the white adipose depots themselves, has provided a basis for studying new opportunities, both for counteracting the development of obesity and perhaps even for diminishing it in already obese persons. However, these cells do not express all the genes found in classical brown adipocytes, and they display a distinctive ontogeny and specific anatomical location. Thus, this particular adipose cell-type cannot be classified as either brown or white. It is the goal of the studies described here to gain insight into the functional significance of the distinct populations of brite/beige adipocytes, seeking to elucidate the functional significance of distinct populations of brite/beige adipocytes; the functional significance of particular brite/beige adipocyte-selective genes; the potential therapeutic benefit of brite/beige adipocytes. We will investigate the following parameters: 1) Functional characterization of brite adipocytes by evaluating the thermogenic UCP1-dependent activity and energy substrate utilization, 2) Gene-specific expression and regulation in beige/brite and brown adipocytes, and 3)  Potential therapeutic benefit of brite/beige adipocytes in systemic glucose and lipid metabolism and insulin sensitivity. Considering the vast medical implications of the obesity epidemic, even modest amelioration of energy balance may be of significance. The studies of brite/beige adipocytes proposed here could represent one means of developing methods to accomplish such amelioration. (AU)