We had been able to reproducibly crystallize and most crystallographic

Using new technology, T 5601640 recent studies have demonstrated the presence of metabolically active BAT in adults. Cold temperature stimulates BAT activation and increases energy expenditure. Furthermore, BAT activation is correlated with decreased adiposity in humans. Therefore, BAT activation has been proposed as a potential new therapeutic approach for obesity. Cold TC-H 106 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 energy metabolism and 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-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. Surprisingly, between successive rounds of cold exposure in the ICE protocol, we observed re-expansion of adiposity to a level beyond the basal level of the preceding cycle.

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