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White Adipose Tissue Proteins Linked to Diabetes, Exercise Training in Proteomics Study

NEW YORK – With proteomic profiling on subcutaneous white adipose tissue, a Danish research team has tracked down protein shifts that coincide with individuals' weight, type 2 diabetes (T2D) status, exercise training, and related clinical or metabolic traits.

As they reported in Science Advances on Wednesday, researchers at the University of Copenhagen, Odense University Hospital, and the University of Southern Denmark relied on a high-throughput, high-sensitivity proteomics pipeline to assess levels of almost 3,800 proteins in white adipose tissue from subcutaneous abdominal adipose tissue samples collected from four dozen biologically male individuals before and after eight weeks of a high-intensity training (HIIT) program in individuals.

The participants included 15 and 18 glucose-tolerant men classified as "obese" or "lean," respectively, based on their body mass index (BMI) measures, along with 15 obese men with T2D. All of the individuals reported that they had low or moderate physical activity levels before the study kicked off the HIIT program, an increasingly lengthy series of cycling and rowing blocks completed three times a week over eight weeks total.

"The number of training blocks was gradually increased from two to five during the intervention period as a block was added every second week," the authors explained. "Halfway through the HIIT protocol, the workload was adjusted according to a VO2 max test to maintain the relative workload and intensity throughout the training period."

Across all three groups, individuals attended at least 95 percent of the HIIT sessions offered to them during the intervention, the team reported, noting that the exercise program was linked to an increase in participants' maximum oxygen consumption (VO2 max) (a measure of cardiovascular endurance) and a significant increase in insulin sensitivity in individuals with or without T2D.

Even so, the HIIT program had only a modest impact on participants' weight or their white adipose tissue proteome. While the researchers saw a dip in total fat mass ranging from around 3.5 to five pounds after the exercise intervention, lean body mass increases were more moderate.

On the proteome side, meanwhile, the most marked HIIT-related changes the team found with its liquid chromatography-tandem mass spectrometry-centered pipeline involved light and heavy chains of the iron storage protein ferritin, which, in turn, showed strong ties to insulin sensitivity.

Most other proteome patterns in the white adipose samples resembled those found prior to the HIIT training — from weight-related protein markers that distinguished lean from heavier participants to more pronounced T2D-associated protein markers that also tracked with insulin sensitivity and levels of the blood sugar marker HbA1c.

"Together, we report a proteomic signature of [white adipose tissue] related to obesity and T2D and highlight an unrecognized role of the human [white adipose tissue] iron metabolism in exercise training adaptations," the authors wrote.

Although the authors cautioned that the current findings are descriptive rather than mechanistic, results from the study and other published work suggests that the shifts in white adipose tissue levels of ferritin subunits after the HIIT intervention may serve to stave off oxidative stress to adipocyte cells.

They noted that "further research with larger cohort sizes is needed to validate and build upon" the subcutaneous white adipose tissue proteome patterns linked to obesity, T2D, and HIIT, and suggested that the high-throughput proteomics workflow used for white adipose tissue analyses in the current study "is well suited for larger-scale studies."