Fat storage‐inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes

What is it about?

Adipose tissue dysfunction has been associated with type 2 diabetes (T2DM). There is now increased focus on understanding the regulation of adipocyte function in the pathogenesis of T2DM and its complications. Fat storage-inducing transmembrane protein 2 (FIT2) is known to play a prominent role in lipid droplet formation in adipose tissue (AT) in mice, by mediating the partitioning of cellular triglycerides (TAG) into lipid droplets. However, the role of FIT2 in regulating human adipocyte function remains unclear. Here, we hypothesize that failure to partition TAGs of the setting of FIT2 protein deficiency, would lead to impaired TAG storage in cytoplasm and thus contribute to the etiology of insulin resistance and T2DM. Interestingly, we found that FIT2 protein is less abundant in subcutaneous and omental AT obtained from patients with T2DM, compared to non-T2DM controls. Insulin signalling was impaired and lipid accumulation were reduced considerably in FIT2 knockdown (KD) adipocytes. FIT2 KD adipocytes showed a trend towards increased inflammation and ER stress as well as reduced glucose uptake. Our results demonstrated for the first time that FIT2 protein is associated with T2DM in humans and plays an integral role in maintaining metabolically healthy adipose function. Our manuscript provides valuable insights by demonstrating that even a partial deficiency of FIT2 protein is detrimental to the function of mature human adipocytes. Understanding the mechanisms will help identify new targets and provide the rationale for developing pharmaceutical agents that target LD formation to target obesity-related metabolic disorders.

Featured Image