These four canonical BVT.2733 pathways were the top pathways responding to the 4 hours of cold exposure based on their significances compared to controls. It has been documented that PKA, PI3K/AKT and ERK/MAPK signaling pathways were altered in BAT following adrenergic agonist stimulation. Given the fact that the effect of cold exposure on the BAT is substantially mediated by the sympathetic system, it is not unexpected to see the changes of these three canonical pathways in the BAT of rats after the 4 hours of cold exposure. Our data showed that the insulin signaling pathway was the most affected canonical pathway responding to 4 hours of cold exposure. Since the up-regulated transcripts were much greater than the down-regulated transcripts, this change suggested that the direction of the insulin signaling pathway was likely up. This was further supported by our western blotting data of insulin signaling and is Camalexin consistent with the chronic cold exposure study of Gasparetti et al. Physiologically, it is likely that the functioning brown adipose tissue in normal mammals responds to cold environments by increasing energy consumption for the short term and increasing the number of mature brown adipocytes for the long term. Carbohydrates are a major energy source for a physiological response to the cold in BAT. Cameron and Smith reported that cold induced the multilocular cells of BAT to lose their lipid vacuoles and led to a decrease in their size in the first 6 to 12 hours of cold exposure, but these features are restored to normal by 24 hours of cold exposure. Cell proliferation, as estimated by the DNA synthetic index method, appeared in the brown fat at 1 day of cold exposure, became maximal at 4 days of cold exposure, and returned to the control level by 16 days of cold exposure. Rat studies have demonstrated that cold exposure decreased insulin secretion. Improving the insulin receptor signaling pathway is likely an important mechanism for brown adipose tissue to obtain glucose more efficiently in the setting of cold-induced hypoinsulinemia.