In mammals, adipose tissue
is a specialized tissue that functions as the major storage site for fat. When glucose supplies are low (for example when an organism is food-deprived), the stored fat can be used to produce energy, so that the organism may be constantly supplied of the fuel it needs to survive. For this purpose, mammals possess two different types of adipose tissue: (i) white fat, used to store metabolic energy (necessary for organisms' physiological activities) and (ii) brown fat, specialized in storing energy that will be used to generate heat in mammalian new-borns and adult hibernating mammals.
Across the animal kingdom, brown fat is essential to avoid hypothermia and is of great importance as cold is a major death risk factor for premature infants. Brown fat is indeed the site of the thermogenesis
, a process of heat production mainly regulated by the sympathetic nervous system
and triggered by cold conditions.
In developed countries, food availability and high sugar-content diets have dramatically increased the rate of food-related diseases, the most widespread of them being obesity
. Obesity itself represents a major epidemiologic challenge associated with a higher incidence of a number of diseases including diabetes, cardiovascular disease, and cancer. Since brown fat can be readily "eliminated" by the organism through thermogenesis, several research groups investigated (i) the presence and abundance of brown fat in adults, and (ii) the possibility of increasing the total amount of brown fat, or by turning white fat into brown fat.
While tackling the above-mentioned questions, a group of scientists from different Universities has analysed the fat depots in mouse models. This led to the isolation of a new type of fat cells termed beige fat
. This particular name has been chosen because these cells showed features of both white and brown fat cells. Importantly, given the fact that beige cells shared brown fat's capacity to produce heat, they have been described as a novel type of thermogenic fat cells. The experiments that lead to the identification of the beige adipocytes, started from the observation that some subcutaneous
(white) adipose depots had characteristics more similar to those of brown fat cells than to those of white adipose tissues. Moreover, the level of a protein significantly responsible for heat production called UCP1 or thermogenin
(normally abundant in brown cells and very low in white cells) was demonstrated to be different between white tissues derived from different locations. This evidence led the scientists to reconsider and rename several tissues (previously defined as white fat) as beige fat.
Among the different techniques that scientists used to discriminate between different tissues, a procedure called RT-PCR
, able to measure the activity of different genes, was used to compare the activity of UCP1
(the gene producing thermogenin) and others genes in the three fat tissues. This provided the group of scientists with the evidence that beige cells show a unique genetic profile. Following these results, the amount of chemical and thermal energy produced by different types of fat cells, was assessed using a technique called micro-respirometry
. This was done to further discriminate between white and brown/beige cells. Then, human brown fat biopsies were analysed for the presence of both brown and beige markers. In order to identify molecules that are typically present in beige or brown tissues, their distribution was visualized using immunofluorescence
, a technique that takes advantage of engineered fluorescent proteins able to recognize and label the target molecules. In doing this, the authors were able to specifically target and visualize beige fat cells and they were able to map their distribution in the different biopsies.
In summary, this research demonstrated for the first time, the unexpected existence of beige fat and its abundance in adult mammals. Before such results were published, it was assumed that there was too little brown fat present in human adults to use it as an indirect mean to reduce body weight. Because of that, the discovery of abundant beige fat with similar characteristics to those of brown fat, has been a remarkable breakthrough in this field of research. Consistently, the results reported in this research are still used as a reference for several biomedical research studies that investigate the use of brown and beige cells for the treatment of obesity and metabolic diseases1-2.