Publication Date:
2018
Description:
〈h3〉Abstract〈/h3〉
〈span〉
〈h3〉Background〈/h3〉
〈p〉Energy homeostasis is regulated by the hypothalamus but fails when animals are fed a high-fat diet (HFD), and leptin insensitivity and obesity develops. To elucidate the possible mechanisms underlying these effects, a microarray-based transcriptomics approach was used to identify novel genes regulated by HFD and leptin in the mouse hypothalamus.〈/p〉
〈/span〉
〈span〉
〈h3〉Results〈/h3〉
〈p〉Mouse global array data identified 〈em〉serpinA3N〈/em〉 as a novel gene highly upregulated by both a HFD and leptin challenge. In situ hybridisation showed 〈em〉serpinA3N〈/em〉 expression upregulation by HFD and leptin in all major hypothalamic nuclei in agreement with transcriptomic gene expression data. Immunohistochemistry and studies in the hypothalamic clonal neuronal cell line, mHypoE-N42 (N42), confirmed that alpha 1-antichymotrypsin (α〈sub〉1〈/sub〉AC), the protein encoded by 〈em〉serpinA3〈/em〉, is localised to neurons and revealed that it is secreted into the media. 〈em〉SerpinA3N〈/em〉 expression in N42 neurons is upregulated by palmitic acid and by leptin, together with 〈em〉IL-6〈/em〉 and 〈em〉TNFα〈/em〉, and all three genes are downregulated by the anti-inflammatory monounsaturated fat, oleic acid. Additionally, palmitate upregulation of 〈em〉serpinA3〈/em〉 in N42 neurons is blocked by the NFκB inhibitor, BAY11, and the upregulation of 〈em〉serpinA3N〈/em〉 expression in the hypothalamus by HFD is blunted in IL-1 receptor 1 knockout (〈em〉IL-1R1〈/em〉〈sup〉〈em〉−/−〈/em〉〈/sup〉) mice.〈/p〉
〈/span〉
〈span〉
〈h3〉Conclusions〈/h3〉
〈p〉These data demonstrate that 〈em〉serpinA3〈/em〉 expression is implicated in nutritionally mediated hypothalamic inflammation.〈/p〉
〈/span〉
Print ISSN:
1555-8932
Electronic ISSN:
1865-3499
Topics:
Biology
,
Medicine
,
Process Engineering, Biotechnology, Nutrition Technology
