Essential Role of STAT3 in Body Weight and Glucose Homeostasis

Yunxia Cui, Lu Huang, Florent Elefteriou, Guoqing Yang, John M. Shelton, Jerald E. Giles, Orhan K. Oz, Tiffany Pourbahrami, Christopher Y H Lu, James A. Richardson, Gerard Karsenty, Cai Li

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113 Scopus citations

Abstract

STAT3 is a ubiquitous transcription factor that is indispensable during early embryogenesis. To study the functions of STAT3 postnatally, we generated conditional STAT3-deficient mice. To that end, STAT3lox/lox mice were crossed with mice expressing Cre under the control of rat insulin II gene promoter (RIP-Cre mice). Immunohistochemical and Western blot analyses showed that STAT3 is deleted from β cells in the islets of Langerhans. Genomic DNA PCR revealed that STAT3 deletion also occurred in the hypothalamus. Hypothalamic Cre expression was further confirmed by crossing RIP-Cre/STAT3 lox/lox mice with the ROSA26 Cre reporter strain and staining for lacZ activity. Double immunohistochemical staining confirmed that deletion of STAT3 occurred in leptin receptor (OB-Rb isoform)-positive neurons. RIP-Cre/STAT3lox/lox mice are mildly hyperglycemic and hyperinsulinemic at the time of weaning, become hyperphagic immediately after weaning, and exhibit impaired glucose tolerance. Body weight, body fat, and mRNA and protein levels of leptin are all significantly increased in RIP-Cre/STAT3lox/lox mice. Administration of recombinant leptin by intracerebroventricular infusion failed to cause complete loss of body fat in RIP-Cre/STAT3lox/lox mice. Transplantation of wild-type islets into RIP-Cre/STAT3lox/lox mice also failed to decrease adiposity or to correct other abnormalities in these mice. These data thus suggest that loss of STAT3 in the hypothalamus caused by RIP-Cre action likely interferes with normal body weight homeostasis and glucose metabolism.

Original languageEnglish (US)
Pages (from-to)258-269
Number of pages12
JournalMolecular and cellular biology
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Cui, Y., Huang, L., Elefteriou, F., Yang, G., Shelton, J. M., Giles, J. E., Oz, O. K., Pourbahrami, T., Lu, C. Y. H., Richardson, J. A., Karsenty, G., & Li, C. (2004). Essential Role of STAT3 in Body Weight and Glucose Homeostasis. Molecular and cellular biology, 24(1), 258-269. https://doi.org/10.1128/MCB.24.1.258-269.2004