SCH 221510 Together, these results indicate that in-between cold exposures, ICE mice increased lipogenesis in liver and WAT to offset cold-induced consumption of TG toward thermogenesis. This adaptive process manifested as increased fat mass of ICE mice. Adipose tissue can expand through hypertrophy and/or hyperplasia. Our study showed that ICE increased the mass of both inguinal and epididymal fat. Consistent with previous reports, beige cells were detected mainly in the inguinal fat of ICE-treated mice. Apparently, beige cell recruitment only partially explains the ICEinduced fat tissue expansion. The reason for cold-induced subcutaneous fat specific browning is not clear. Although cold exposure activates SNS in almost all adipose depots, norepinephrine turnover rates were higher in inguinal fat than epididymal fat. Since SNS plays a critical role in beige cells recruitment in WAT, higher norepinephrine turnover rates may contribute to the browning in inguinal fat. By analyzing white adipocyte cellular areas, we found that adipocytes of inguinal fat of ICE-treated mice were significant larger than that of control mice, while the opposite was true for epididymal fat. These results indicate WAT depot selectivity of ICEinduced metabolic adaptation. This THIP hydrochloride finding is not surprising given the well-documented regional difference in adipocyte biology. Subcutaneous adipocytes are less active in lipolysis than visceral adipocytes and do not undergo hyperplasia in response to cold exposure. We therefore postulate lipolytic resistance, coupled with enhanced lipogenesis, results in lipid accumulation of inguinal adipocytes in ICE mice. In contrast, epididymal adipocytes were smaller than those in control mice, suggesting that the expansion of epididymal fat pad in ICE mice was primarily due to increased adipogenesis. This notion is further supported by the finding of significantly elevated adipogenic transcription factors C/EBPa and PPARc. In addition, a recent study also demonstrated that even an overnight cold exposure induces adipocytes recruitment in epididymal fat. We therefore propose that ICE-induced epididymal fat enlargement is mainly due to hyperplasia. Energy balance plays a critical role in controlling fat accumulation. Cold exposure induces food intake in rodents. Our study indeed showed that ICE transiently increased food intake.