Characterization of Tusc5, an adipocyte gene co-expressed in peripheral neurons

Tumor suppressor candidate 5 (Tusc5, also termed brain endothelial cell derived gene-1 or BEC-1), a CD225 domain-containing, cold-repressed gene identified during brown adipose tissue (BAT) transcriptome analyses was found to be robustly-expressed in mouse white adipose tissue (WAT) and BAT, with similarly high expression in human adipocytes. Tusc5 mRNA was markedly increased from trace levels in pre-adipocytes to significant levels in developing 3T3-L1 adipocytes, coincident with several mature adipocyte markers (phosphoenolpyruvate carboxykinase 1, GLUT4, adipsin, leptin). The Tusc5 transcript levels were increased by the peroxisome proliferator activated receptor-γ (PPARγ) agonist GW1929 (1 μg/mL, 18 h) by >10-fold (pre-adipocytes) to ∼1.5-fold (mature adipocytes) versus controls (p < 0.0001). Taken together, these results suggest an important role for Tusc5 in maturing adipocytes. Intriguingly, we discovered robust co-expression of the gene in peripheral nerves (primary somatosensory neurons). In light of the marked repression of the gene observed after cold exposure, these findings may point to participation of Tusc5 in shared adipose-nervous system functions linking environmental cues, CNS signals, and WAT-BAT physiology. Characterization of such links is important for clarifying the molecular basis for adipocyte proliferation and could have implications for understanding the biology of metabolic disease-related neuropathies.