Unlike leptin, ciliary neurotrophic factor does not reverse the starvation-induced changes of serum corticosterone and hypothalamic neuropeptide levels but induces expression of hypothalamic inhibitors of leptin signaling
| Autor: | Christian Bjørbæk, Stanley M. Hileman, Christos S. Mantzoros, Mary Ziotopoulou, David M. Erani |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Leptin
Male medicine.medical_specialty Pro-Opiomelanocortin Endocrinology Diabetes and Metabolism Hypothalamus Neuropeptide Gene Expression Suppressor of Cytokine Signaling Proteins Biology Ciliary neurotrophic factor chemistry.chemical_compound Mice Corticosterone Internal medicine Internal Medicine medicine Animals Agouti-Related Protein Neuropeptide Y SOCS3 Ciliary Neurotrophic Factor RNA Messenger Leptin receptor digestive oral and skin physiology Body Weight Neuropeptides Proteins Fasting Neuropeptide Y receptor Actins DNA-Binding Proteins Isoenzymes Mice Inbred C57BL Repressor Proteins Endocrinology chemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Suppressor of Cytokine Signaling 3 Protein biology.protein Trans-Activators Intercellular Signaling Peptides and Proteins hormones hormone substitutes and hormone antagonists Transcription Factors |
| Zdroj: | Diabetes. 49(11) |
| ISSN: | 0012-1797 |
| Popis: | Leptin mediates neuroendocrine responses to fasting and restores the starvation-induced changes of several hypothalamic neuropeptides. Ciliary neurotrophic factor (CNTF), a cytokine closely related to leptin, reduces food intake and reverses obesity, but its role in restoring the starvation-induced changes of hormones or hypothalamic neuropeptides remains largely unknown. To comparatively assess the roles of CNTF and leptin in reversing the starvation-induced changes of hypothalamic neuropeptides and endocrine function and in inducing expression of hypothalamic inhibitors of leptin and CNTF signaling (suppressor of cytokine signaling 3 [SOCS-3]) and mediators of energy expenditure (cyclo-oxygenase 2 [COX-2]), we studied the effect of CNTF and leptin administered by intraperitoneal injections (1 microg/g twice daily) in C57Bl/6J mice fasted for 48 h. Serum corticosterone levels increased with fasting, and leptin administration partially normalized them, whereas CNTF administration had no effect. Hypothalamic neuropeptide Y (NPY) and agouti-related protein (AgRP) mRNA expression increased and pro-opiomelanocortin (POMC) decreased in response to fasting. Leptin administration decreased NPY and AgRP and increased POMC mRNA levels toward baseline, but CNTF administration in fasted mice had no effect of comparable significance. Both leptin and CNTF administration in fasted mice resulted in an induction of SOCS-3 mRNA expression. CNTF also induced hypothalamic SOCS-2 mRNA expression. Finally, neither leptin nor CNTF administration in mice fasted for 48 h alters hypothalamic COX-2 expression. Our data suggest that only falling leptin levels mediate the starvation-induced alterations in corticosterone levels and expression of hypothalamic neuropeptides, but inhibitors of leptin signaling are induced by both leptin and CNTF. This may be of clinical importance because both agents are now being evaluated for the treatment of obesity in humans. |
| Databáze: | OpenAIRE |
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