RT Journal Article
T1 Interleukin 6 Deficiency Modulates the Hypothalamic Expression of Energy Balance Regulating Peptides during Pregnancy in Mice
A1 Pazos Mendoza, Patricia
A1 Lima Rodríguez, Luis
A1 Casanueva Freijo, Felipe
A1 Diéguez González, Carlos
A1 García García, María del Carmen
AB Pregnancy is associated with hyperphagia, increased adiposity and multiple neuroendocrine adaptations. Maternal adiposetissue secretes rising amounts of interleukin 6 (IL6), which acts peripherally modulating metabolic function and centrallyincreasing energy expenditure and reducing body fat. To explore the role of IL6 in the central mechanisms governing dam’senergy homeostasis, early, mid and late pregnant (gestational days 7, 13 and 18) wild-type (WT) and Il6 knockout mice (Il6-KO) were compared with virgin controls at diestrus. Food intake, body weight and composition as well as indirectcalorimetry measurements were performed in vivo. Anabolic and orexigenic peptides: neuropeptide Y (Npy) and agoutirelated peptide (Agrp); and catabolic and anorectic neuropeptides: proopiomelanocortin (Pomc), corticotrophin andthyrotropin-releasing hormone (Crh and Trh) mRNA levels were determined by in situ hybridization. Real time-PCR andwestern-blot were used for additional tissue gene expression and protein studies. Non-pregnant Il6-KO mice were leanerthan WT mice due to a decrease in fat but not in lean body mass. Pregnant Il6-KO mice had higher fat accretion despitesimilar body weight gain than WT controls. A decreased fat utilization in absence of Il6 might explain this effect, as shownby increased respiratory exchange ratio (RER) in virgin Il6-KO mice. Il6 mRNA levels were markedly enhanced in adiposetissue but reduced in hypothalamus of mid and late pregnant WT mice. Trh expression was also stimulated at gestationalday 13 and lack of Il6 blunted this effect. Conversely, in late pregnant mice lessened hypothalamic Il6 receptor alpha (Il6ra),Pomc and Crh mRNA were observed. Il6 deficiency during this stage up-regulated Npy and Agrp expression, while restoringPomc mRNA levels to virgin values. Together these results demonstrate that IL6/IL6Ra system modulates Npy/Agrp, Pomcand Trh expression during mouse pregnancy, supporting a role of IL6 in the central regulation of body fat in thisphysiological state.
PB PLOS
YR 2013
FD 2013
LK http://hdl.handle.net/10347/21811
UL http://hdl.handle.net/10347/21811
LA eng
NO Pazos P, Lima L, Casanueva FF, Diéguez C, García MC (2013) Interleukin 6 Deficiency Modulates the Hypothalamic Expression of Energy Balance Regulating Peptides during Pregnancy in Mice. PLoS ONE 8(8): e72339. https://doi.org/10.1371/journal.pone.0072339
NO This work was funded by European Community, Ministerio de Economía y Competitividad and Xunta de Galicia grants (MCGG and CD: ERG-516456; MCGG and PP: BFU2007-62683/BFI; MCGG and LL:PGIDIT06PXIB208067PR). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII. The research leading to these results has also received funding from the European Community's Seventh Framework Programme under grant agreements (CD: Health-F2-2008-223713: “Reprobesity”; FP7/2007-2013: n° 245009: “NeuroFAST”)
DS Minerva
RD 26 abr 2026