At present, the main method to evaluate BAT is with 18F-FDG PET-CT, however, this method uses ionizing radiation, limiting its application. 18F-FDG PET-CT detects glucose tissue uptake, which could be affected by external factors, such as serum glucose levels, diets, and environmental temperatures. All of these factors could cause BAT concentrations to be underestimated [21]. Recently, MRI begins to be used in BAT research studies as a nonradioactive imaging method. Since BAT has been shown to have different fractions of fatty acids and water content compared with those of WAT, BAT and WAT tissues can be distinguished by MRI[10].
Although many studies have been published on the relationship between exercise and BAT, this relationship is still controversial. In our study, interscapular BAT V/W ratios were higher in the running group than that in the control group, which demonstrated that running exercise promoted BAT proliferation. The result of our study was similar to those of several previous studies [19, 17, 14, 16], whose subjects included rats and mice, and the exercises included swimming and running.
At present, the relatively accepted pathway of BAT activation during exercise is that the SNS is stimulated. The result is that target proteins, such as hormone-sensitive lipase, triglyceride lipase, and monoacylglycerol lipase, are phosphorylated, promoting the degradation of triglycerides in adipocytes and releasing free fatty acids to activate UCP1, resulting in increased thermogenesis [22–24]. Peres Valgas da Silva et al. showed that mature brown adipocytes from exercise-trained BAT had reduced glucose uptake in the absence of innervation, demonstrating that neural innervation is greatly significant for BAT functions [25].
However, some studies have shown that exercise decreases BAT activity [18, 15]. In one study, male rats, subjected to moderately intense treadmill running to replicate endurance exercise, had decreased thermogenic capacities in classic BAT. In this study, the BAT of the trained rats had decreased UCP1 expression and a reduction in fatty acids, indicating that exercise decreased BAT activity. From a physiologic perspective, the authors surmised that increased BAT activity during exercise did not seem reasonable. In this theory, since BAT is a thermogenic tissue, its activation during exercise might seem like a waste of energy since exercise consumes energy and produces heat. To keep the body temperature stable, BAT activity would need to be inhibited.
In human studies looking at the impact of exercise on BAT also showed conflicting results. One study evaluated BAT activity in endurance-trained athletes by using 18F-FDG PET-CT. Compared to the control group, endurance-trained athletes showed lower cold-induced BAT [26]. However, in another 18F-FDG PET-CT study of 40 cancer patients, increased habitual physical exercise (light exercise) led to higher BAT activity [2].
We speculate that there could be several reasons for the conflicting results. First, different exercises, such as swimming and running, could have varying results. For instance, swimming, as opposed to running, could result in a loss of heat due to the body's contact with water, thereby activating the thermogenic function of BAT. Second, there could be a difference in the duration and intensity of exercise. In previous studies, both short-term exercise and long-term endurance training have been evaluated. Whether these exercises can activate BAT compensatory mechanisms remains unclear. Third, different assessment methods could lead to different results. 18F-FDG PET-CT is one method that is affected by several variables, including ambient temperatures, blood glucose levels, and diet. If these variables are not well controlled, BAT quantities would be likely underestimated. Free fatty acids (FFA) have also been shown to be the main substrate for BAT thermogenesis [20], and, therefore, it is doubtful if 18F-FDG PET-CT can truly reflect BAT metabolism. Moreover, the evaluation of BAT volumes using MRI is still in the exploratory stages, more studies and samples are required to standardize the evaluation methods.
In our study, we found that the mice in running group had higher interscapular BAT T2 values than those in the control group. We speculated that the increased T2 values in our study were mainly due to the increased BAT volume. That is to say, the interstitial components increased as the volume of BAT increased, leading to more water content in tissue. Secondly, due to long-term exercise stimulating BAT through the SNS, and with BAT oxygen supplies fully compensated, more oxyhemoglobin would be available in this region, results in an increase of the T2 values. Our study showed that BAT volume correlated positively with BAT T2 value. The change of T2 value may reflect the change of BAT volume to a certain extent, as the distribution of BAT in human is relatively scattered, making it difficult to measure[27].
There are some limitations to our study. First, there was a disparity in the number of mice in the running group compared with the number in the control group, which was primarily caused by a lack of preparation in the early selection of mice, with an excessive number of mice that refused to exercise. Second, our study is considered preliminary, lacking protein and gene expression analyses, which will be performed in future studies.