KLF7 induced ADRB3-dependent IL-6 production in brown adipocytes during stress
Maodi Liang, Meixiu Zhang, Yanting Hou, Fangyuan Yuan, Huizi Zhang, Mengyuan Zhao, Lili Xu, Qin Liu, Yurui Su, Xiaolong Chu, Wei Li, Jingzhou Wang, Jianxin Xie, Cuizhe Wang, Qinghua Cui, Jun Zhang
TL;DR
Stress increases IL-6 production in brown fat cells through a pathway involving KLF7 and ADRB3, which could help explain how the body responds to stress.
Contribution
This study identifies KLF7 as a novel mediator of ADRB3-dependent IL-6 production in brown adipocytes during stress.
Findings
KLF7 is required for ADRB3-induced IL-6 production in brown adipocytes during stress.
CREB activates KLF7 transcription, which in turn increases IL-6 expression in response to ADRB3 activation.
cAMP-PKA-CREB signaling mediates stress-induced IL-6 production in brown adipocytes.
Abstract
In recent studies, acute physiological stress has been shown to enhance liver gluconeogenesis by activating β3-adrenergic receptor (ADRB3)-dependent interleukin-6 (IL-6) production in brown adipocytes, effectively fueling “fight or flight” responses. However, the specific molecular mechanism of this IL-6 production in an ADRB3-dependent manner is not fully understood. ADRB3 regulates multiple metabolic programs in adipose tissue, including thermogenesis, lipolysis, and glucose uptake, by activating cAMP-PKA-CREB signaling. Our previous studies revealed that the transcription factor Krüppel-like factor 7 (KLF7) transcriptionally induces IL-6 expression in white adipocytes. Using Klf7-adipocyte knockout mice, we showed that Klf7 is also required for ADRB3-induced IL-6 production during stress. cAMP-PKA-CREB signaling mediates this transduction via stress and ADRB3 agonist administration…
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Taxonomy
TopicsKruppel-like factors research · Adipokines, Inflammation, and Metabolic Diseases · Adipose Tissue and Metabolism