Cold-Induced mRNA Expression of Angiogenic Factors in Rat Brown Adipose Tissue

Brown adipose tissue (BAT) is the major site of non-shivering thermogenesis in rodents. Rapid angiogenesis is induced in association with adaptive hyperplasia of this tissue when the animal is exposed to cold. We demonstrated previously adrenergic activation of mRNA expression of vascular endothelial growth factor (VEGF) in rat BAT and its possible contribution to the cold-induced angiogenesis in this tissue. In the present study, we examined the effect of cold exposure on mRNA expression of other two angiogenic factors, VEGF-B and basic fibroblast growth factor (bFGF), in rats. Conventional Northern blot analysis revealed abundant mRNA expression of VEGF-B as well as VEGF, but not bFGF, in BAT. When rats were exposed to cold at 4 degrees C, the VEGF mRNA level was increased by 2.7-fold in 1-4 hr and returned to the basal level within 24 hr. In contrast, the VEGF-B mRNA level did not change throughout the course of cold exposure. A significant expression of bFGF mRNA was detected in BAT by reverse transcription-polymerase chain reaction (RT-PCR). To evaluate the tissue bFGF mRNA level quantitatively, a competitive RT-PCR method was developed using a shorter RNA fragment as a competitor. The bFGF mRNA level in BAT was found to increase by 2.3-fold in 4 hr and decreased to the basal level within 24 hr after cold exposure. These results suggest that cold exposure leads to induce VEGF and bFGF rapidly and transiently in BAT, which in turn stimulate the proliferation of vascular endothelial cells in this tissue.