DNA-binding activity of STAT3 increased in hypothalamus of DIO mice; the reduction of STAT3 phosphorylation may facilitate leptin signaling
| Autor: | Guoli Zhou, Huimin Liu, Guoqing Yang, Wanping Lu, Ran Yang, Hao Li, Liang Xu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Leptin
Male STAT3 Transcription Factor 0301 basic medicine endocrine system medicine.medical_specialty Pro-Opiomelanocortin Mutant Hypothalamus Biophysics Gene Expression Mice Obese FOXO1 Diet High-Fat Biochemistry Energy homeostasis 03 medical and health sciences Basal (phylogenetics) Cell Line Tumor Internal medicine medicine Animals Humans Obesity Phosphorylation STAT3 Molecular Biology Diminution biology Chemistry digestive oral and skin physiology DNA Cell Biology Mice Inbred C57BL HEK293 Cells 030104 developmental biology Endocrinology biology.protein hormones hormone substitutes and hormone antagonists Protein Binding Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 505:229-235 |
| ISSN: | 0006-291X |
| Popis: | Leptin-mediated DNA-binding activity of STAT3 in hypothalamus plays crucial roles in the maintenance of energy homeostasis in lean mice; however its effects still remains unclear in case of leptin resistance in mice with diet induced obesity (DIO). In this study significant elevation of both basal and exogenously leptin-treated DNA-binding activity of STAT3 was detected using EMSA in the hypothalamus of male C57BL/6J mice fed high-fat diet for 10 wks, in concomitant with hyperleptinemia, high body weight, high fat mass, and hyperphagia as well as decreased POMC expression. The studies in vitro showed that both DNA binding activity and the proximal SBE of POMC promoter was essential to leptin-mediated POMC expression. However, the diminution of STAT3 phosphorylation, achieved by S3I-201 or a FoxO1 mutant, facilitated leptin-mediated POMC expression. The findings here demonstrated excess STAT3 activity negatively regulated POMC expression in hypothalamus of DIO mice, and suggested the limitation of STAT3 activity may promote leptin signaling. |
| Databáze: | OpenAIRE |
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