Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 1107 56

Although obesity is associated with a state of leptin resistance, it has been suggested that leptin may contribute to the pathogenesis of obesity-related hypertension. In previous studies, we reported that cafeteria diet feeding induces hyperleptinaemia and hyperinsulinemia in both male and female rats, with hypertension occurring only in male rats. However, when female rats were neonatally treated with testosterone (T), these animals develop hypertension when fed the cafeteria diet. These observations led us to investigate leptin signaling and some neuropeptides that are leptin targets in the hypothalamus of male, intact female, and T-treated female cafeteria diet-fed rats. A decrease in the hypothalamic leptin receptors (Ob-Ra and Ob-Rb) and pro-opiomelanocortin (POMC) mRNA was observed only in male hypertensive cafeteria diet-fed rats. Although no alterations in Ob-R occurred in both groups of female cafeteria diet-fed rats, the hyperleptinaemic state of these animals had no influence on POMC mRNA levels. In intact female rats, expression of the suppressors of cytokines signaling SOCS-1, SOCS-2, SOCS-3, and cytokine inhibitor signaling were unaltered, whereas in T-treated females SOCS-3 was overexpressed. Finally SOCS-1 mRNA level was increased only in male rats. Because hyperinsulinemia was reported to counteract the leptin-induced stimulation of the sympathetic tone and because SOCS-1 and -3 are potential inhibitors of insulin signaling, our results suggest that the hypothalamic overexpression of SOCS-1 or SOCS-3 found in male or T-treated female rats after cafeteria diet feeding could block the negative influence of the hyperinsulinemia on the central pressor action of leptin, thereby contributing to their hypertensive state.
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PMID:Hypothalamic leptin receptor and signaling molecule expressions in cafeteria diet-fed rats. 1296 51