RT Journal Article
T1 SerpinA3N is a novel hypothalamic gene upregulated by a high-fat diet and leptin in mice
A1 Sergi, Domenico
A1 Campbell, Fiona M.
A1 Grant, Christine
A1 Morris, Amanda C.
A1 Bachmair, Eva María
A1 Koch, Christiane
A1 McLean, Fiona H.
A1 Muller, Aifric
A1 Hoggard, Nigel
A1 Roos, Baukje de
A1 Porteiro Couto, Begoña
A1 Boekschoten, Mark V.
A1 McGillicuddy, Fiona C.
A1 Kahn, Darcy
A1 Nicol, Phyllis
A1 Benzler, Jonas
A1 Mayer, Claus-Dieter
A1 Drew, Janice E.
A1 Roche, Helen M.
A1 Muller, Michael
A1 Nogueiras Pozo, Rubén
A1 Diéguez González, Carlos
A1 Tups, Alexander
A1 Williams, Lynda M.
K1 SerpinA3N
K1 Hypothalamus
K1 High-fat diet
K1 Leptin
AB BackgroundEnergy 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.ResultsMouse global array data identified serpinA3N as a novel gene highly upregulated by both a HFD and leptin challenge. In situ hybridisation showed serpinA3N 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 (α1AC), the protein encoded by serpinA3, is localised to neurons and revealed that it is secreted into the media. SerpinA3N expression in N42 neurons is upregulated by palmitic acid and by leptin, together with IL-6 and TNFα, and all three genes are downregulated by the anti-inflammatory monounsaturated fat, oleic acid. Additionally, palmitate upregulation of serpinA3 in N42 neurons is blocked by the NFκB inhibitor, BAY11, and the upregulation of serpinA3N expression in the hypothalamus by HFD is blunted in IL-1 receptor 1 knockout (IL-1R1−/−) mice.ConclusionsThese data demonstrate that serpinA3 expression is implicated in nutritionally mediated hypothalamic inflammation
PB BMC
SN 1555-8932
YR 2018
FD 2018
LK http://hdl.handle.net/10347/22137
UL http://hdl.handle.net/10347/22137
LA eng
NO Sergi, D., Campbell, F.M., Grant, C. et al. SerpinA3N is a novel hypothalamic gene upregulated by a high-fat diet and leptin in mice. Genes Nutr 13, 28 (2018)
NO LMW, CG, ACM, EB, AM, BdR, MVB, MM and C-DM were supported by a project grant from NuGO; LMW, AM and FHM were supported by a project support grant from the British Society for Neuroendocrinology; DS was supported by a SULSA studentship; FHM was supported by a EASTBIO DTP BBSRC studentship; LMW, CG, ACM, EB, BdR, C-DM, FMC, PN, JED and NH were funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS). AT and KC were funded by the German Ministry of Research and Education (Ref. No: 0315087). HMR was supported by the Irish Department of Agriculture, Food and Marine ImmunoMet Programme (14/F/828). FCM and HMR were supported by Science Foundation Ireland Principal Investigator Programme (11/PI/1119). RN and CD were supported by grants from Ministerio de Economia y Competitividad (CD: BFU2011-29102; RN: BFU2012-35255), Xunta de Galicia (RN: EM 2012/039 and 2012-CP069). Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBERobn). CIBERobn is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. The research leading to these results has also received funding from the European Community’s Seventh Framework Programme under the following grants: no 245009: NeuroFAST to CD and ERC StG-2011-OBESITY53-281408 to RN
DS Minerva
RD 24 abr 2026