Foxc2 coordinates inflammation and browning of white adipose by leptin-STAT3-PRDM16 signal in mice

作者：Gan, L.; Liu, Z.; Feng, F.; Wu, T.; Luo, D.; Hu, C.; Sun, C.^*

来源：International Journal of Obesity, 2018, 42(2): 252-259.

DOI：10.1038/ijo.2017.208

• INSULIN-RESISTANCE
• ADIPOCYTE DIFFERENTIATION
• BODY-WEIGHT
• TISSUE
• LEPTIN
• FAT
• OBESITY
• TRANSCRIPTION-3
• TRANSDUCER
• ACTIVATION

AIMS: The objective of this study is to characterize the relationship between forkhead box C2 protein (Foxc2) and leptin under adipose inflammatory response. @@@ METHODS: Lipopolysaccharide (LPS)-induced inflammatory model was conducted. Data from wild-type and ob/ob mice were used to compare the alternative role of leptin on Foxc2-mediated inflammation and browning. Transcriptional regulation and proteinprotein interaction were analyzed by bioinformatics and proved by chromatin immunoprecipitation and co-immunoprecipitation experiment. @@@ RESULTS: Foxc2 and leptin correlated with inflammation and browning of white adipose tissue (WAT) in LPS-treated mice. Moreover, Foxc2-mediated inhibition of inflammation involved downstream activation of leptin signal and promoted WAT browning. We then determined CREB, the potential transcriptional factor of leptin, was required for Foxc2-mediated inflammation in the regulation of WAT browning. Foxc2 alleviated adipocyte inflammation by reducing leptin-mediated Janus-activated kinase 2/signal transducer and activator of transcription 3 (STAT3) pathway. Importantly, STAT3 physically interacted with PRDM16 and formed a complex to promote WAT browning. Exogenous Foxc2 overexpression also ameliorated inflammation and promoted adipose browning in high fat diet (HFD)-induced obese mice. @@@ CONCLUSIONS: Our results indicated that Foxc2 inhibited inflammation and promoted browning of WAT through positive regulation of leptin signal and the STAT3-PRDM16 complex. These findings identify a new potential means to prevent and treat obese caused metabolic syndrome of mammals.

• 出版日期2018-2
• 单位西北农林科技大学