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dc.contributor.authorChristina N., Heiss
dc.date.accessioned2022-04-11T08:19:57Z
dc.date.available2022-04-11T08:19:57Z
dc.date.issued2022-04-11
dc.identifier.isbn978-91-8009-724-6 (PDF)
dc.identifier.isbn978-91-8009-723-9 (print)
dc.identifier.urihttps://hdl.handle.net/2077/70539
dc.description.abstractThe gut microbiota can affect development and metabolism in the host. Today, much is still unknown regarding the effects of the gut microbiota on central energy balance regulation. We used mouse models to determine the role of the gut microbiota in diet- induced hypothalamic inflammation as well as in hypothalamic development. We found that mice lacking a gut microbiota do not develop diet-induced hypothalamic inflammation. Using genetically modified mice lacking glucagon-like peptide-1- receptor (GLP-1R) as well as pharmacological inhibition of GLP-1R signaling, we could show that this protection requires functional GLP-1R signaling. We further found that astrocytic GLP-1R signaling mediates at least parts of the observed protection. Next, we determined the role of gut microbiota and gut microbial signaling on blood- brain barrier (BBB) function in the mediobasal hypothalamus (MBH). The gut bacteria did not alter BBB function, as assessed by the number of cells in contact to the circulation, by tight junction protein staining, and by administration of a neurotoxin. In contrast, mice lacking the Toll-like receptor (TLR) adaptor protein Myd88 had an altered BBB function. Lastly, we determined whether the gut microbiota affects the early postnatal leptin surge with neurotrophic effects. Germ-free (GF) mice had a significantly elevated and prolonged leptin surge, but we observed no long-lasting differences between GF and conventionally-raised mice in the neuronal projections regulating energy balance. In conclusion, our results contribute to new insights within the field of neuroinflammation and identify central GLP-1R signaling as a potential target for modulation of neuroinflammation. Furthermore, our studies suggest that signaling via the TLR adaptor protein Myd88 can be targeted to modulate BBB permeability in the MBH. Lastly, the elevated postnatal leptin surge observed in GF mice warrant further studies determining potential functional consequences in the host.en
dc.language.isoengen
dc.relation.haspartPaper I: Heiss CN, Mannerås-Holm L, Lee YS, Serrano-Lobo J, Håkansson Gladh A, Seeley RJ, Drucker DJ, Bäckhed F, Olofsson LE. The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism. Cell Reports, 2021; https://doi.org/10.1016/j.celrep.2021.109163en
dc.relation.haspartPaper II: Heiss CN, Gravert E, Hulten M, Olofsson LE. Myd88-deficiency, but not gut microbiota depletion, is sufficient to modulate the blood-brain barrier function in the mediobasal hypothalamus. Accepted for publication in Molecular Neurobiology, 2022en
dc.relation.haspartPaper III: Heiss CN, Lilla P, Olofsson LE. Role of the gut microbiota in the postnatal leptin surge and development of hypothalamic circuits regulating energy balance. Manuscripten
dc.subjectgut microbiotaen
dc.subjectenergy balance regulationen
dc.subjecthypothalamic inflammationen
dc.subjectastrocytesen
dc.subjectblood-brain barrieren
dc.subjectneuronsen
dc.titleThe role of the gut microbiota in central energy balance regulationen
dc.typetexteng
dc.type.svepDoctoral thesiseng
dc.gup.mailchristina.heiss@wlab.gu.seen
dc.type.degreeDoctor of Philosophy (Medicine)en
dc.gup.originUniversity of Gothenburg. Sahlgrenska Academyen
dc.gup.departmentInstitute of Medicine. Department of Molecular and Clinical Medicineen
dc.gup.defenceplaceTorsdagen den 5 Maj 2022, kl 9.00, Hörsal Arvid Carlsson, Academicum, Medicinaregatan 3, Göteborgen
dc.gup.defencedate2022-05-05
dc.gup.dissdb-fakultetSA


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