A missing link in the puzzle: Brown adipose tissue^†

We read with great interest the review by Fabbrini et al.,1 and we thought it is a valuable contribution. We are willing to shift the attention to another area related to metabolic syndrome and obesity.

Brown adipose tissue (BAT) is present in some animals permanently, particularly in rodents. In humans, BAT is found predominantly in newborns and young children and is thought to be a rudimentary tissue in adult humans. Although white adipose tissue (WAT) stores extra energy as triacylglycerol, BAT scatters energy as heat via uncoupling protein-1 (UCP1), a proton transporter which is available only in the inner mitochondrial membrane of brown adipocytes.2 In contrast to WAT, which has been intensely studied, the importance of BAT in humans was unknown and had been poorly studied until recently. With the understanding of BAT availability in humans,3-5 some metabolic consequences regarding metabolic syndrome and obesity have been extracted from related clinical studies. We could think of BAT as a heat producer and fat burner in the body that creates a negative energy balance. It is clear that such an effect will result in weight loss independent of other parameters such as exercise or dietary caloric intake. Cypess et al.3 reported that BAT activity is lower in obese individuals compared to lean subjects. In the same study, male and female subjects have different amount of BAT. Women were found to have higher amounts of BAT than in men. This might be an explanation of why men are sensitive to obesity-related complications such as atherosclerosis, beyond other known factors (hormonal, genetic, environmental). Virtanen et al.,5 by using fluoro-deoxyglucose positron emission tomography scan, also observed that a higher amount of BAT is inversely correlated with obesity with aging. We also learned that many animal studies evaluating the relation of obesity and BAT demonstrated that BAT activity and UCP1 expression are important parameters for developing obesity and insulin resistance.2, 6-8

With this knowledge of BAT, targeted therapies are on the way. This may be possible either through induction of already available BAT (with beta agonism and cold) in the body or changing the genetic structure for differentiating tissue from the preadipocyte phase to BAT, involving peroxisome proliferator-activated receptor-γ and other transcriptional regulators such as PR domain–containing 16.2, 9 Petrovic et al.10 treated primary cultures of mouse brown preadipocytes with rosiglitazone and found that it is a useful strategy to recruit brown adipocytes from preadipocytes.

As the authors mentioned in the review, some obese patients are metabolically normal and do not have a fatty liver. In addition, some patients with fatty liver who have no extra risk factors from other patients have a poor prognosis and rapidly progress to end-stage liver disease. We generally think that obesity, metabolic syndrome, and fatty liver are well-known variables in obesity pathogenesis. However, it is obvious that there are some overlooked points in the equation. In this regard, BAT may be an explanation. It may serve as both a prognostic and therapeutic tool for clinicians.11 The association between fatty liver and BAT has never been studied before, and we thought that future studies will reveal the role of BAT in nonalcoholic fatty liver disease. In addition, we believe that BAT is a promising target for coping with obesity and its complications.