Therefore, BAT activation has been proposed as a potential new therapeutic approach for obesity. Cold exposure activates BAT thermogenesis. However, prolonged exposure to cold in humans has been limited by cardiovascular and respiratory complications. Therefore, repetitive or intermittent cold exposure may be a more realistic approach to activate BAT in humans. Although cold exposure and ICE have been used in rodents and even human subjects, their effects on systemic Ro 01-6128 energy metabolism and R 568 hydrochloride adiposity are not fully understood. For rodents, many studies reported that cold exposure enhances both fatty acid oxidation and glucosederived lipogenesis in BAT, but its effects on WAT were controversial. Furthermore, contradictory effects on body weight and WAT have been observed in both mice and rats. For humans, although ICE enhances BAT recruitment, its effects on systemic adiposity have been controversial. Therefore, it is necessary to clarify the effect of cold exposure on body fat before applying ICE to treat obesity. Here, by using C57BL/6 mice, we have investigated whether and how ICE alters adiposity. Similar to human subjects and rats, ICE induced BAT recruitment in mice. Unexpectedly, ICE induced fat accumulation, an effect that cannot be attributed to hyperphagia or stress. Remarkably, ICE induced lipogenic gene expression in both WAT and liver during the non-exposure period. Therefore, our results demonstrate that in spite of inducing BAT recruitment, ICE increases de novo lipogenesis in WAT and liver then enhances fat accumulation in mice. BAT activation has been suggested to increase energy expenditure and improve glucose and lipid metabolism, especially in the obese state. However, our study showed that ICE did not significantly alter glycemic levels either in the fasting state or after challenge with insulin or glucose. These results suggest that ICE does not alter basal systemic insulin sensitivity or glucose homeostasis in mice. Since insulin is important in regulating lipogenesis, which was enhanced in liver and WAT of ICE mice, the results of glucose and insulin challenge test cannot rule out the improvement of insulin sensitivity in liver and WAT. We also found that ICE led to an increase of serum triglycerides and a trend toward increased free fatty acid levels in serum, albeit not reaching statistical significance. BAT-mediated thermogenesis is a calorie-consuming process that might be utilized to correct the energy surplus that underlies obesity in humans. Consistent with previous studies, our study indeed showed that ICE increases BAT recruitment. In addition, we found a significant reduction of body fat within hours of cold exposure in both our ACE and ICE protocols.