Transcriptional dynamics in type 2 diabetes progression is linked with circadian, thermogenic, and cellular stress in human adipose tissue

The prevalence of type 2 diabetes (T2D) has increased significantly over the past three decades, with an estimated 30-40% of cases remaining undiagnosed. Brown and beige adipose tissues, known for their remarkable catabolic capacity, can lower blood glucose levels. Beige adipose tissue can be differentiated from adipose stem cells or through transdifferentiation from white adipose tissue. However, the impact of T2D progression on beige adipocyte functional capacity remains unclear. Transcriptomic profiling of subcutaneous adipose tissue biopsies from healthy normal-weight, healthy obese, prediabetic obese, and obese T2D patients revealed a progressive alteration in cellular processes associated with catabolic metabolism, circadian rhythms, thermogenesis-related signaling pathways, cellular stress, and inflammation. MAX was identified as a potential transcription factor linking inflammation with the circadian clock and thermogenesis during T2D progression. This study unveils a previously unrecognized transcriptional circuit that increasingly disrupts subcutaneous adipose tissue oxidative capacity during T2D progression. These findings could open new research avenues for developing chronopharmaceutical strategies to treat and prevent T2D.