Acetate supplementation increases brain acetyl-CoA and attenuates lipopolysaccharide (LPS)-induced neuroinflammation in vivo. To explain the anti-inflammatory effect of acetate treatment, we proposed that acetate treatment disrupts inflammatory signaling in microglia and astrocytes, and induces histone hyperacetylation known to be correlated with anti-inflammatory properties. To test this hypothesis, we measured the effects that LPS and acetate treatment had on histone acetylation, mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and eicosanoid signaling. A single oral dose of acetate treatment (6 g/kg) in normal animals induced a time- and site-specific pattern of histone hyperacetylation, associated with reduction of histone deacetylase (HDAC) activity and expression. Long-term acetate treatment over 28 days induced the same site-specific pattern of histone hyperacetylation, and reversed LPS-induced histone H3 at lysine 9 (H3K9) hypoacetylation and interleukin (IL)-1β expression. In LPS-stimulated BV-2 microglia, acetate treatment reversed LPS-induced H3K9 hypoacetylation, IL-1β, IL-6, tumor necrosis factor (TNF)-α, cyclooxygenase (Cox)-1 and 2 protein levels, and NF-κB p65 protein level and phosphorylation at serine 468. Further, acetate treatment increased IL-4 and transforming growth factor (TGF)-β1 expression, and NF-κB p65 acetylation at lysine 310. Conversely, acetate treatment did not alter LPS-induced
cytosolic (c) phospholipase A2 (PLA2), transiently reduced MAPK p38 and JNK phosphorylation, and increased MAPK ERK1/2 phosphorylation. In LPS-stimulated astrocyte, acetate treatment induced H3K9 hyperacetylation, reversed LPS-induced increases in IL-1β, TNF-α, NF-κB p65, and Cox-1 protein levels, MAPK p38 and cPLA2 phosphorylation and PGE2 release, and reversed LPS-induced decreases in TGF-β1 and IL-4. Moreover, acetate treatment reduced basal levels of IL-6, phosphorylated ERK1/2 and NF-κB p65 at serine 536, sPLA2 IIA and PLCβ1. Acetate treatment also increased acetylated H3K9 bound to the promoters of the genes of Cox-1, Cox-2, IL-1β and NF-κB p65, but not IL-4 in BV-2 microglia, which suggests that acetate treatment-induced H3K9 hyperacetylation can potentially be involved in the alteration of the expression of these genes. These data suggest that acetate treatment has net anti-inflammatory effects in vivo and in vitro both in LPS-stimulated microglia and astrocyte cultures through neuroglial cell type-distinct mechanisms.
","abstract_html":"<p>Acetate supplementation increases brain acetyl-CoA and attenuates lipopolysaccharide (LPS)-induced neuroinflammation in vivo. To explain the anti-inflammatory effect of acetate treatment, we proposed that acetate treatment disrupts inflammatory signaling in microglia and astrocytes, and induces histone hyperacetylation known to be correlated with anti-inflammatory properties. To test this hypothesis, we measured the effects that LPS and acetate treatment had on histone acetylation, mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and eicosanoid signaling. A single oral dose of acetate treatment (6 g/kg) in normal animals induced a time- and site-specific pattern of histone hyperacetylation, associated with reduction of histone deacetylase (HDAC) activity and expression. Long-term acetate treatment over 28 days induced the same site-specific pattern of histone hyperacetylation, and reversed LPS-induced histone H3 at lysine 9 (H3K9) hypoacetylation and interleukin (IL)-1β expression. In LPS-stimulated BV-2 microglia, acetate treatment reversed LPS-induced H3K9 hypoacetylation, IL-1β, IL-6, tumor necrosis factor (TNF)-α, cyclooxygenase (Cox)-1 and 2 protein levels, and NF-κB p65 protein level and phosphorylation at serine 468. Further, acetate treatment increased IL-4 and transforming growth factor (TGF)-β1 expression, and NF-κB p65 acetylation at lysine 310. Conversely, acetate treatment did not alter LPS-induced </p> <p>cytosolic (c) phospholipase A2 (PLA2), transiently reduced MAPK p38 and JNK phosphorylation, and increased MAPK ERK1/2 phosphorylation. In LPS-stimulated astrocyte, acetate treatment induced H3K9 hyperacetylation, reversed LPS-induced increases in IL-1β, TNF-α, NF-κB p65, and Cox-1 protein levels, MAPK p38 and cPLA2 phosphorylation and PGE2 release, and reversed LPS-induced decreases in TGF-β1 and IL-4. Moreover, acetate treatment reduced basal levels of IL-6, phosphorylated ERK1/2 and NF-κB p65 at serine 536, sPLA2 IIA and PLCβ1. Acetate treatment also increased acetylated H3K9 bound to the promoters of the genes of Cox-1, Cox-2, IL-1β and NF-κB p65, but not IL-4 in BV-2 microglia, which suggests that acetate treatment-induced H3K9 hyperacetylation can potentially be involved in the alteration of the expression of these genes. These data suggest that acetate treatment has net anti-inflammatory effects in vivo and in vitro both in LPS-stimulated microglia and astrocyte cultures through neuroglial cell type-distinct mechanisms.</p>","abstract_has_math":false,"creators":["Soliman, Mahmoud Lotfy"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":["Thad A. Rosenberger"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-01-01T08:00:00Z","date_published":"2012-01-01T08:00:00Z","updated_at":"2026-07-24T03:26:24Z","subjects":["acetate, acetylation, epigenetics, glia, neuroinflammation, signaling"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://commons.und.edu/theses/1379","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Thad A. Rosenberger"]},{"key":"dc:creator","label":"Author","values":["Soliman, Mahmoud Lotfy"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["acetate, acetylation, epigenetics, glia, neuroinflammation, signaling"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://commons.und.edu/theses/1379"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Acetate supplementation increases brain acetyl-CoA and attenuates lipopolysaccharide (LPS)-induced neuroinflammation in vivo. To explain the anti-inflammatory effect of acetate treatment, we proposed that acetate treatment disrupts inflammatory signaling in microglia and astrocytes, and induces histone hyperacetylation known to be correlated with anti-inflammatory properties. To test this hypothesis, we measured the effects that LPS and acetate treatment had on histone acetylation, mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and eicosanoid signaling. A single oral dose of acetate treatment (6 g/kg) in normal animals induced a time- and site-specific pattern of histone hyperacetylation, associated with reduction of histone deacetylase (HDAC) activity and expression. Long-term acetate treatment over 28 days induced the same site-specific pattern of histone hyperacetylation, and reversed LPS-induced histone H3 at lysine 9 (H3K9) hypoacetylation and interleukin (IL)-1β expression. In LPS-stimulated BV-2 microglia, acetate treatment reversed LPS-induced H3K9 hypoacetylation, IL-1β, IL-6, tumor necrosis factor (TNF)-α, cyclooxygenase (Cox)-1 and 2 protein levels, and NF-κB p65 protein level and phosphorylation at serine 468. Further, acetate treatment increased IL-4 and transforming growth factor (TGF)-β1 expression, and NF-κB p65 acetylation at lysine 310. Conversely, acetate treatment did not alter LPS-induced
cytosolic (c) phospholipase A2 (PLA2), transiently reduced MAPK p38 and JNK phosphorylation, and increased MAPK ERK1/2 phosphorylation. In LPS-stimulated astrocyte, acetate treatment induced H3K9 hyperacetylation, reversed LPS-induced increases in IL-1β, TNF-α, NF-κB p65, and Cox-1 protein levels, MAPK p38 and cPLA2 phosphorylation and PGE2 release, and reversed LPS-induced decreases in TGF-β1 and IL-4. Moreover, acetate treatment reduced basal levels of IL-6, phosphorylated ERK1/2 and NF-κB p65 at serine 536, sPLA2 IIA and PLCβ1. Acetate treatment also increased acetylated H3K9 bound to the promoters of the genes of Cox-1, Cox-2, IL-1β and NF-κB p65, but not IL-4 in BV-2 microglia, which suggests that acetate treatment-induced H3K9 hyperacetylation can potentially be involved in the alteration of the expression of these genes. These data suggest that acetate treatment has net anti-inflammatory effects in vivo and in vitro both in LPS-stimulated microglia and astrocyte cultures through neuroglial cell type-distinct mechanisms.
"]},{"key":"dc:title","label":"Title","values":["Neuroglial Mechanisms Involved In The Anti-Inflammatory Effect Of Acetate Supplementation"]}]}],"canonical_facts":{"dc:contributor":["Thad A. Rosenberger"],"dc:creator":["Soliman, Mahmoud Lotfy"],"dc:description.abstract":["Acetate supplementation increases brain acetyl-CoA and attenuates lipopolysaccharide (LPS)-induced neuroinflammation in vivo. To explain the anti-inflammatory effect of acetate treatment, we proposed that acetate treatment disrupts inflammatory signaling in microglia and astrocytes, and induces histone hyperacetylation known to be correlated with anti-inflammatory properties. To test this hypothesis, we measured the effects that LPS and acetate treatment had on histone acetylation, mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and eicosanoid signaling. A single oral dose of acetate treatment (6 g/kg) in normal animals induced a time- and site-specific pattern of histone hyperacetylation, associated with reduction of histone deacetylase (HDAC) activity and expression. Long-term acetate treatment over 28 days induced the same site-specific pattern of histone hyperacetylation, and reversed LPS-induced histone H3 at lysine 9 (H3K9) hypoacetylation and interleukin (IL)-1β expression. In LPS-stimulated BV-2 microglia, acetate treatment reversed LPS-induced H3K9 hypoacetylation, IL-1β, IL-6, tumor necrosis factor (TNF)-α, cyclooxygenase (Cox)-1 and 2 protein levels, and NF-κB p65 protein level and phosphorylation at serine 468. Further, acetate treatment increased IL-4 and transforming growth factor (TGF)-β1 expression, and NF-κB p65 acetylation at lysine 310. Conversely, acetate treatment did not alter LPS-induced
cytosolic (c) phospholipase A2 (PLA2), transiently reduced MAPK p38 and JNK phosphorylation, and increased MAPK ERK1/2 phosphorylation. In LPS-stimulated astrocyte, acetate treatment induced H3K9 hyperacetylation, reversed LPS-induced increases in IL-1β, TNF-α, NF-κB p65, and Cox-1 protein levels, MAPK p38 and cPLA2 phosphorylation and PGE2 release, and reversed LPS-induced decreases in TGF-β1 and IL-4. Moreover, acetate treatment reduced basal levels of IL-6, phosphorylated ERK1/2 and NF-κB p65 at serine 536, sPLA2 IIA and PLCβ1. Acetate treatment also increased acetylated H3K9 bound to the promoters of the genes of Cox-1, Cox-2, IL-1β and NF-κB p65, but not IL-4 in BV-2 microglia, which suggests that acetate treatment-induced H3K9 hyperacetylation can potentially be involved in the alteration of the expression of these genes. These data suggest that acetate treatment has net anti-inflammatory effects in vivo and in vitro both in LPS-stimulated microglia and astrocyte cultures through neuroglial cell type-distinct mechanisms.
"],"dc:identifier":["https://commons.und.edu/theses/1379"],"dc:subject":["acetate, acetylation, epigenetics, glia, neuroinflammation, signaling"],"dc:title":["Neuroglial Mechanisms Involved In The Anti-Inflammatory Effect Of Acetate Supplementation"],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T03:26:24Z"}