O., Fernández-Gayol P., Sanchis K., Aguilar A., Navarro-Sempere G., Comes A., Molinero M., Giralt J., Hidalgo Supplementary Material for: Different Responses to a High-Fat Diet in IL-6 Conditional Knockout Mice Driven by Constitutive GFAP-Cre and Synapsin 1-Cre Expression <b><i>Background/Aims:</i></b> Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, at least in part through actions in the central nervous system (CNS) from local sources. <b><i>Methods:</i></b> We herewith report results obtained in conditional IL-6 KO mice for brain cells (<i>Il6</i><sup><i>ΔGfap</i></sup> and <i>Il6</i><sup><i>ΔSyn</i></sup>). <b><i>Results:</i></b> The reporter RiboTag mouse line demonstrated specific astrocytic expression of GFAP-dependent Cre in the hypothalamus but not in other brain areas, whereas that of synapsin 1-dependent Cre was specific for neurons. Feeding a high-fat diet (HFD) or a control diet showed that <i>Il6</i><sup><i>ΔGfap</i></sup> and <i>Il6</i><sup><i>ΔSyn</i></sup> mice were more prone and resistant, respectively, to HFD-induced obesity. Energy intake was not altered in HFD experiments, but it was reduced in <i>Il6</i><sup><i>ΔSyn</i></sup> male mice following a 24-h fast. HFD increased circulating insulin, leptin, and cholesterol levels, decreased triglycerides, and caused impaired responses to the insulin and glucose tolerance tests. In <i>Il6</i><sup><i>ΔGfap</i></sup> mice, the only significant difference observed was an increase in insulin levels of females, whereas in <i>Il6</i><sup><i>ΔSyn</i></sup> mice the effects of HFD were decreased. Hypothalamic <i>Agrp</i> expression was significantly decreased by HFD, further decreased in <i>Il6</i><sup><i>ΔGfap</i></sup>, and increased in <i>Il6</i><sup><i>ΔSyn</i></sup> female mice. Hypothalamic <i>Il-6</i> mRNA levels were not decreased in <i>Il6</i><sup><i>ΔSyn</i></sup> mice and even increased in <i>Il6</i><sup><i>ΔGfap</i></sup><sup></sup>male mice. Microarray analysis of hypothalamic RNA showed that female <i>Il6</i><sup><i>ΔGfap</i></sup> mice had increased interferon-related pathways and affected processes in behavior, modulation of chemical synaptic transmission, learning, and memory. <b><i>Conclusion:</i></b> The present results demonstrate that brain production of IL-6 regulates body weight in the context of caloric excess and that the cellular source is critical. IL-6;GFAP-Cre;Synapsin 1-Cre;Body weight;High-fat diet;Insulin;Leptin;Growth hormone;RiboTag 2019-06-11
    https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Different_Responses_to_a_High-Fat_Diet_in_IL-6_Conditional_Knockout_Mice_Driven_by_Constitutive_GFAP-Cre_and_Synapsin_1-Cre_Expression/8255768
10.6084/m9.figshare.8255768.v1