Lindsay Callesen posted an update 6 days, 12 hours ago
Therefore, the decreased apoptosis revealed in the present study, associated with already published previous data that have shown the capacity of the adipose cells to produce cytokines and its plasticity, could lead to insights for further research that may explain the complete role of MAT in CD. Obesity is a metabolic disease characterized by overexpansion of white adipose tissue. Although genetic predisposition is important in the development of obesity, chronic positive energy balance has been considered the main cause of obesity in the general population. Therefore, correcting energy imbalance is an ideal therapy for obesity. Unfortunately, commonly used therapeutic approaches such as dieting and exercise are not efficient at containing the obesity epidemic. WAT and BAT are the two main types of fat in mammals. WAT is the primary energy depot that stores energy as triglyceride-enriched lipid droplets. By contrast, BAT is considered as an energy dispenser that consumes significant amounts of chemical energy toward thermogenesis. Due to its inconspicuous appearance in adult humans, BAT was previously thought to exist only in infants. Using new technology, 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 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 SDZ 220-581 hydrochloride 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. This finding of a net increase in fat mass in our ICE mice is in line with a previous mouse study, but is at variance with several ICE rodent studies and the two recent human studies, which either detected a reduction of body fat after 6 weeks of daily 2 h cold exposure or observed no change in adiposity after 10 days of a similar ICE protocol. The discordance is likely multifactorial and may include differences in species and experimental protocols. However, unlike these studies that measured body weight or single fat pad mass at the end of study, we used the highly accurate MRI approach to track body composition throughout the course of ICE treatment. We revealed dynamic changes of body fat during and after cold exposure. Our studies demonstrate that despite enhancing BAT recruitment and decreasing of fat mass during cold exposure, the overall consequence of ICE is fat accumulation in mice. Another important finding of this study is that cold exposure profoundly impacts not only BAT but also liver and WAT, which might play a critical role in expanding adiposity between cold exposure periods. Under physiological conditions, cold exposure induces a series of responses from various organs to maintain body temperature, including BAT activation and TG mobilization. Consistent with previous reports, our study showed that cold exposure dramatically increased HSL phosphorylation levels in WAT, indicative of increased lipolysis. Concomitantly, the lipogenic transcription factor SREBP1c was reduced in both WAT and liver. These results further confirm the notion that during cold exposure, energy consuming process of lipogenesis is suppressed while FA release from WAT is enhanced to fuel thermogenesis in BAT. The rapid decrease of fat mass during cold exposure further supports it. Interestingly, our study also demonstrated compensatory fat accumulation during the non-cold exposure period. The oscillation of fat mass during ICE is mirrored by the expression levels of key lipogenic genes in both WAT and liver. These results suggest a stimulatory effect of ICE on de novo lipogenesis during the non-exposure period. The liver is an important organ for lipid metabolism, where fatty acids are synthesized and/or reesterificated and incorporated into TGenriched lipoproteins for transport to WAT and other tissues. We found both liver TG content and hepatic TG export were increased in ICE-treated mice. 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.