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Somatostatin, a negative‐regulator of central leptin action in the rat hypothalamus
Author(s) -
Stepanyan Z.,
Kocharyan A.,
Behrens M.,
Koebnick C.,
Pyrski M.,
Meyerhof W.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04219.x
Subject(s) - medicine , endocrinology , leptin , somatostatin , hypothalamus , leptin receptor , somatostatin receptor , biology , energy homeostasis , neuropeptide , somatostatin receptor 2 , receptor , chemistry , obesity
Leptin‐responsive neurons of the hypothalamus constitute a heterogeneous population expressing a vast array of different neuropeptides and neurotransmitters, some of which participate in the regulation of hunger and satiety. Here we report that somatostatin modulates the efficacy of leptin‐signalling in the rat hypothalamus. Using a two‐pulse paradigm at 30‐min intervals, we delivered somatostatin or somatostatin receptor subtype‐selective agonists in combination with leptin into the lateral cerebral ventricle of stereotaxically cannulated rats. To monitor the effect of somatostatin on the leptin‐signalling pathway, we quantified changes in the leptin‐mediated activation of STAT3, the signal transducer and activator of transcription 3. Successive administration of somatostatin and leptin diminished the level of STAT3‐phosphorylation and nuclear STAT3 translocation in the ventromedial and dorsomedial hypothalamic nuclei, the lateral hypothalamic area, and the arcuate nucleus by about 40% compared to leptin administration alone. Furthermore, application of subtype‐selective somatostatin receptor agonists suggests that the observed reduction in leptin‐responsiveness is predominantly mediated by the sst3 receptor‐subtype, followed by sst1 and sst2. In addition, the intensity of the negative‐regulatory effect of somatostatin on leptin‐signalling displayed regional differences for the three receptor‐subtypes involved. Addressing the functional consequences of the diminished leptin‐signalling, behavioural analyses showed that centrally applied somatostatin counteracts the leptin‐mediated suppression of food intake. These results suggest that the pleiotropic effector somatostatin also plays a role in the central regulation of energy homeostasis.