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  • The development of obesity is identified closely related to


    The development of obesity is identified closely related to energy metabolism. Brown adipose tissue is the main heat-producing tissue [13]. UCP1 promotes mitochondrial ATP production, and stimulates a series of respiratory chain reaction, subsequently contributes to thermogenesis in BAT [13,54]. Besides, UCP1 is also expressed in the white adipose tissue and regulates energy metabolism [54]. In this study, we found that the expression of UCP1 was up-regulated, and the thermogenic program was activated in the white adipose tissue. This upregulation of UCP1 is most likely due to the elevated beige cell-selective markers of SAT. The regulation of heat production in adipocytes is complex, and several transcription factors are involved in the process. PGC1α was a significant regulator of heat production in brown adipose tissue [55]. In white adipose tissue, PGC1α can also mediate the expression of thermogenesis genes such as UCP1 and reflects the activity of thermogenic [13]. In our study, the expression of PGC1α in both brown and subcutaneous white adipose tissues is significantly increased. These results suggested that Filipin Complex activates PGC1a and promotes the heat production. Another involved important transcriptional regulator is PRDM16, which regulates the differentiation of brown adipocytes into mature brown adipocytes. With PRDM16 knocked out, heat production is decreased in BAT [56,57]. PRDM16 is highly expressed in visceral adipocyte tissue (VAT), promotes the development of brown-like adipocytes, and plays a vital role in regulating the metabolism and thermogenesis in SAT [58]. In our study, PRDM16 expression in BAT and SAT of asthmatic mice is significantly increased, which may promote the metabolism and thermogenesis. However, whether asthma-induced high IgE mediates PRDM16 expression is not studied from the cellular perspect. AMPK is an important energy metabolism regulator that can enhance Sirt1 activity. Both AMPK and Sirt1 mediate the expression of PGC1α [[19], [20], [21]]. AMPK/Sirt1/PGC1α constitute an energy sensing network that controls energy expenditure [59]. In our study, asthma-activated AMPK/PGC1α signaling increases brown fat thermogenesis, and promotes SAT into beige fat. Further study is needed to identify the role of asthma-induced high IgE in the activation of AMPK and Sirt1. Our results showed no significant difference in fasting blood glucose level and serum insulin level between the control and asthmatic mice, but a significant increase in the systemic insulin sensitivity in asthmatic mice. Insulin mainly acts on the adipose tissue, liver, and muscle. Previous studies showed that IgE inhibited the expression of pAKT in visceral adipose tissue [60], suggesting that visceral white adipose tissue might not be involved in the improvement of insulin sensitivity in asthmatic mice. In our hands, asthma downregulated the expression of liver G6Pase while upregulted expression of liver pAKT. These data together suggest that asthma-induced high IgE may regulate insulin sensitivity by suppressing gluconeogenesis. Reducing hepatic gluconeogenesis is important for enhancing hepatic insulin sensitivity and improving hyperglycemia [61]. However, some reports exist conflicting about glycogen synthesis in liver in diabetes. Some results showing that Hepatic insulin resistance decrease glycogen synthesis [62], and others studies indicate that glycogen synthesis was not affected [63]. In our study, we didn't assess the contents of glycogen in liver between the two groups. The change of glycogen synthesis in the liver of asthmatic mice is still unclear.
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    Acknowledgement This work was financially supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (grant number: 2016-I2M-1-006), the National Natural Science Foundation of China (grant numbers: 81622008, 81470579, 91739107), Thousand Young Talents Program of China.