Interleukin-6 actions in the hypothalamus protects against obesity and is involved in the regulation of neurogenesis.
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Date
2021
Authors
Bóbbo, Vanessa Cristina Dias
Engel, Daiane Fátima
Jara, Carlos Poblete
Mendes, Natália Ferreira
Tovolli, Roberta Haddad
Prado, Thais P.
Oliveira, Davi Sidarta
Morari, Joseane
Velloso, Licio Augusto
Araújo, Eliana Pereira
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Abstract
Background: Interleukin-6 (IL6) produced in the context of exercise acts in the hypothalamus reducing obesity-
associated inflammation and restoring the control of food intake and energy expenditure. In the hippocampus,
some of the beneficial actions of IL6 are attributed to its neurogenesis-inducing properties. However, in the
hypothalamus, the putative neurogenic actions of IL6 have never been explored, and its potential to balance
energy intake can be an approach to prevent or attenuate obesity.
Methods: Wild-type (WT) and IL6 knockout (KO) mice were employed to study the capacity of IL6 to induce
neurogenesis. We used cell labeling with Bromodeoxyuridine (BrdU), immunofluorescence, and real-time PCR to
determine the expression of markers of neurogenesis and neurotransmitters. We prepared hypothalamic
neuroprogenitor cells from KO that were treated with IL6 in order to provide an ex vivo model to further
characterizing the neurogenic actions of IL6 through differentiation assays. In addition, we analyzed single-cell RNA
sequencing data and determined the expression of IL6 and IL6 receptor in specific cell types of the murine
hypothalamus.
Results: IL6 expression in the hypothalamus is low and restricted to microglia and tanycytes, whereas IL6 receptor
is expressed in microglia, ependymocytes, endothelial cells, and astrocytes. Exogenous IL6 reduces diet-induced
obesity. In outbred mice, obesity-resistance is accompanied by increased expression of IL6 in the hypothalamus. IL6
induces neurogenesis-related gene expression in the hypothalamus and in neuroprogenitor cells, both from WT as
well as from KO mice.
Conclusion: IL6 induces neurogenesis-related gene expression in the hypothalamus of WT mice. In KO mice, the
neurogenic actions of IL6 are preserved; however, the appearance of new fully differentiated proopiomelanocortin
(POMC) and neuropeptide Y (NPY) neurons is either delayed or disturbed.
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Keywords
Cytokine, Metabolism, Neuron, Astrocyte, Brain
Citation
BÓBBO, V. C. D. et al. Interleukin-6 actions in the hypothalamus protects against obesity and is involved in the regulation of neurogenesis. Journal of Neuroinflammation, v. 18, 2021. Disponível em: <https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-021-02242-8>. Acesso em: 11 out. 2022.