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dc.contributor.authorMcEwan, Hayden
dc.contributor.authorInglis, Megan
dc.contributor.authorQuennell, Janette
dc.contributor.authorGrattan, David
dc.contributor.authorAnderson, Greg
dc.date.available2016-02-22T01:43:55Z
dc.date.copyright2016
dc.identifier.citationMcEwan, H., Inglis, M., Quennell, J., Grattan, D., & Anderson, G. (2016). Deletion of suppressor of cytokine signaling 3 from forebrain neurons delays infertility and onset of hypothalamic leptin resistance in response to a high fat and high sucrose diet. Journal of Neuroscience.en
dc.identifier.urihttp://hdl.handle.net/10523/6230
dc.descriptionThis archive contains supplementary material to the main paper published in Journal of Neuroscience.en_NZ
dc.description.abstractThe cellular processes that cause high fat and sugar diet-induced infertility are poorly understood, but may involve up-regulation of suppressor of cytokine signalling (SOCS-3) proteins which leads to hypothalamic leptin resistance. Deletion of SOCS-3 from brain cells is known to protect mice from diet-induced obesity, but the effects on diet-induced infertility are unknown. We utilized neuron-specific SOCS3 knockout mice to elucidate this and the effects on regional hypothalamic leptin resistance. As expected, male and female neuron-specific SOCS3 knockout mice were protected from high fat and sucrose diet (HFD)-induced obesity. Female knockout mice did not become infertile after 4 months of HFD feeding as did their wild-type counterparts, and also did not exhibit leptin resistance onset in the medial preoptic area and anteroventral periventricular nucleus, regions important for generation of the surge of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) that induces ovulation. We therefore tested whether the suppressive effects of HFD on the estradiol-induced GnRH/LH surge suppression were overcome by neuron-specific SOCS3 knockout. While only 20% of control HFD-mice experienced a preovulatory-like LH surge, LH surges could be induced in almost all neuron-specific SOCS3 knockout mice on this diet. In contrast to females, HFD-fed male mice did not exhibit any decline in fertility compared to low fat and sucrose diet-fed males despite their resistance to the satiety effects of leptin. These data show that deletion of SOCS3 delays the onset of leptin resistance and infertility in HFD-fed female mice, but given continued HFD feeding this state does eventually occur, presumably in response to other leptin inhibitory mechanisms.en_NZ
dc.format.mimetypeapplication/pdf
dc.language.isoenen_NZ
dc.publisherSociety for Neuroscienceen_NZ
dc.relation.ispartofJournal of Neuroscienceen_NZ
dc.titleDeletion of suppressor of cytokine signaling 3 from forebrain neurons delays infertility and onset of hypothalamic leptin resistance in response to a high fat and high sucrose dieten_NZ
dc.typeJournal Articleen_NZ
dc.date.updated2016-02-22T00:15:37Z
otago.schoolAnatomyen_NZ
otago.openaccessOpenen_NZ
dc.rights.statementCopyright © 2004, Journal of Neuroscience, Society for Neuroscience. Any copies of this Journal, in whole or in part, must include the copyright notice. Any use of this Journal in whole or in part should include customary bibliographic citation, including author attribution, date, article title, Neuroscience Online, and the URL http://www.jneurosci.org/ For permissions to copy beyond that permitted by Section 107 or 108 of the U.S. Copyright Law and for reprints, contact the Copyright Clearance Center. The fee code for users of the Transactional Reporting Service appears at the end of each full text article.en_NZ
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