Leptin but not CNTF induces PTP-1B expression in human neuronal cells (SH-SY5Y): putative explanation of CNTF efficacy in leptin-resistant state.
 

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11-15-08 08:15 AM
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Leptin but not CNTF induces PTP-1B expression in human neuronal cells (SH-SY5Y): putative explanation of CNTF efficacy in leptin-resistant state.
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Leptin but not CNTF induces PTP-1B expression in human neuronal cells (SH-SY5Y): putative explanation of CNTF efficacy in leptin-resistant state.

Endocrinology. 2008 Nov 13;

Authors: Benomar Y, Berthou F, Vacher CM, Bailleux V, Gertler A, Djiane J, Taouis M

Growing evidences suggest that obesity is associated with hypothalamic leptin resistance leading to the alteration of food intake control. Alternative treatment using ciliary neurotrophic factor (CNTF) has been suggested, since CNTF exerts a leptin-like effect even in leptin-resistant states, but the mechanisms by which CNTF maintains this effect are not yet understood. Both leptin and CNTF act in the hypothalamus through similar signaling pathways including JAK-2/STAT-3 pathway. To explore the differences and interactions between leptin and CNTF signaling pathways, differentiated human neuroblastoma cells (SH-SY5Y) were exposed to either leptin or CNTF and then challenged for each cytokine. Leptin pre-treatment completely abolished leptin-dependent STAT-3 and ERK 1/2 phosphorylations without affecting CNTF action. The lack of cross-desensitization between leptin and CNTF signaling pathways occurred despite the induction of SOCS-3 in response to both cytokines. Interestingly, leptin as well as insulin induced the expression of PTP-1B, whereas CNTF treatment did not affect its expression. In addition, acute leptin treatment but not CNTF induced PTP-1B expression in mouse hypothalamic arcuate nucleus. Furthermore, the over-expression of human PTP-1B in SH-SY5Y cells completely abolished leptin- and insulin-dependent JAK-2, STAT-3 and ERK 1/2 phosphorylations but CNTF action was not altered. Collectively, our results suggest that PTP-1B constitutes a key divergent element between leptin/insulin and CNTF signaling pathways at the neuronal level, which may constitute a possible mechanism that explains the efficacy of CNTF in leptin resistant states.

PMID: 19008309 [PubMed - as supplied by publisher]