2. Academic Validation
  3. KLF7 induced ADRB3-dependent IL-6 production in brown adipocytes during stress

KLF7 induced ADRB3-dependent IL-6 production in brown adipocytes during stress

  • J Lipid Res. 2026 Feb;67(2):100981. doi: 10.1016/j.jlr.2026.100981.
Maodi Liang 1,  Meixiu Zhang 2,  Yanting Hou 1,  Fangyuan Yuan 1,  Huizi Zhang 1,  Mengyuan Zhao 1,  Lili Xu 1,  Qin Liu 1,  Yurui Su 1,  Xiaolong Chu 3,  Wei Li 1,  Jingzhou Wang 4,  Jianxin Xie 5,  Cuizhe Wang 6,  Qinghua Cui 7,  Jun Zhang 8
Affiliations

Affiliations

  • 1 Department of Medical Genetics, Shihezi University School of Medicine, Shihezi, Xinjiang Province, China.
  • 2 Department of Medical Genetics, Shihezi University School of Medicine, Shihezi, Xinjiang Province, China; Department of Obstetrics, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi Province, China.
  • 3 Department of Medical Genetics, Shihezi University School of Medicine, Shihezi, Xinjiang Province, China; Department of Medical Genetics, Medical College of Tarim University, Xinjiang Province, China.
  • 4 Department of Medical Genetics, Shihezi University School of Medicine, Shihezi, Xinjiang Province, China. Electronic address: [email protected].
  • 5 Department of Medical Genetics, Shihezi University School of Medicine, Shihezi, Xinjiang Province, China; Department of Medical Genetics, Medical College of Tarim University, Xinjiang Province, China. Electronic address: [email protected].
  • 6 Department of Medical Genetics, Shihezi University School of Medicine, Shihezi, Xinjiang Province, China. Electronic address: [email protected].
  • 7 Department of Medical Genetics, Shihezi University School of Medicine, Shihezi, Xinjiang Province, China; School of Sports Medicine, Wuhan Institute of Physical Education, Wuhan, Hubei Province, China. Electronic address: [email protected].
  • 8 Department of Medical Genetics, Shihezi University School of Medicine, Shihezi, Xinjiang Province, China. Electronic address: [email protected].
PMID: 41565113 DOI: 10.1016/j.jlr.2026.100981
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 in a mouse model in vivo, as well as in brown adipocytes cultured in vitro. cAMP response element-binding protein (CREB) positively regulates KLF7 transcription by binding to the promoter of KLF7. These findings indicate that stress-induced IL-6 production is dependent on Klf7 in adipocytes. KLF7, as a target gene of CREB, responds to ADRB3 activation to increase endocrine IL-6 in a cAMP-PKA-CREB signaling-dependent manner. Our study provides a new theoretical basis for elucidating and enriching the novel mechanism of stress-induced IL-6 production in brown adipocytes.

Keywords

ADRB3; IL-6; KLF7; liver gluconeogenesis; stress.

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