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Maternal obesogenic diet enhances cholestatic liver disease in offspring

Human and animal model data show that maternal obesity promotes nonalcoholic fatty liver disease in offspring and alters bile acid (BA) homeostasis. Here we investigated whether offspring exposed to maternal obesogenic diets exhibited greater cholestatic injury. We fed female C57Bl6 mice conventiona...

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Autores principales: Thompson, Michael D., Hinrichs, Holly, Faerber, Austin, Tarr, Phillip I., Davidson, Nicholas O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046959/
https://www.ncbi.nlm.nih.gov/pubmed/35341737
http://dx.doi.org/10.1016/j.jlr.2022.100205
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author Thompson, Michael D.
Hinrichs, Holly
Faerber, Austin
Tarr, Phillip I.
Davidson, Nicholas O.
author_facet Thompson, Michael D.
Hinrichs, Holly
Faerber, Austin
Tarr, Phillip I.
Davidson, Nicholas O.
author_sort Thompson, Michael D.
collection PubMed
description Human and animal model data show that maternal obesity promotes nonalcoholic fatty liver disease in offspring and alters bile acid (BA) homeostasis. Here we investigated whether offspring exposed to maternal obesogenic diets exhibited greater cholestatic injury. We fed female C57Bl6 mice conventional chow (CON) or high fat/high sucrose (HF/HS) diet and then bred them with lean males. Offspring were fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 2 weeks to induce cholestasis, and a subgroup was then fed CON for an additional 10 days. Additionally, to evaluate the role of the gut microbiome, we fed antibiotic-treated mice cecal contents from CON or HF/HS offspring, followed by DDC for 2 weeks. We found that HF/HS offspring fed DDC exhibited increased fine branching of the bile duct (ductular reaction) and fibrosis but did not differ in BA pool size or intrahepatic BA profile compared to offspring of mice fed CON. We also found that after 10 days recovery, HF/HS offspring exhibited sustained ductular reaction and periportal fibrosis, while lesions in CON offspring were resolved. In addition, cecal microbiome transplant from HF/HS offspring donors worsened ductular reaction, inflammation, and fibrosis in mice fed DDC. Finally, transfer of the microbiome from HF/HS offspring replicated the cholestatic liver injury phenotype. Taken together, we conclude that maternal HF/HS diet predisposes offspring to increased cholestatic injury after DDC feeding and delays recovery after returning to CON diets. These findings highlight the impact of maternal obesogenic diet on hepatobiliary injury and repair pathways during experimental cholestasis.
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spelling pubmed-90469592022-05-02 Maternal obesogenic diet enhances cholestatic liver disease in offspring Thompson, Michael D. Hinrichs, Holly Faerber, Austin Tarr, Phillip I. Davidson, Nicholas O. J Lipid Res Research Article Human and animal model data show that maternal obesity promotes nonalcoholic fatty liver disease in offspring and alters bile acid (BA) homeostasis. Here we investigated whether offspring exposed to maternal obesogenic diets exhibited greater cholestatic injury. We fed female C57Bl6 mice conventional chow (CON) or high fat/high sucrose (HF/HS) diet and then bred them with lean males. Offspring were fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 2 weeks to induce cholestasis, and a subgroup was then fed CON for an additional 10 days. Additionally, to evaluate the role of the gut microbiome, we fed antibiotic-treated mice cecal contents from CON or HF/HS offspring, followed by DDC for 2 weeks. We found that HF/HS offspring fed DDC exhibited increased fine branching of the bile duct (ductular reaction) and fibrosis but did not differ in BA pool size or intrahepatic BA profile compared to offspring of mice fed CON. We also found that after 10 days recovery, HF/HS offspring exhibited sustained ductular reaction and periportal fibrosis, while lesions in CON offspring were resolved. In addition, cecal microbiome transplant from HF/HS offspring donors worsened ductular reaction, inflammation, and fibrosis in mice fed DDC. Finally, transfer of the microbiome from HF/HS offspring replicated the cholestatic liver injury phenotype. Taken together, we conclude that maternal HF/HS diet predisposes offspring to increased cholestatic injury after DDC feeding and delays recovery after returning to CON diets. These findings highlight the impact of maternal obesogenic diet on hepatobiliary injury and repair pathways during experimental cholestasis. American Society for Biochemistry and Molecular Biology 2022-03-25 /pmc/articles/PMC9046959/ /pubmed/35341737 http://dx.doi.org/10.1016/j.jlr.2022.100205 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Thompson, Michael D.
Hinrichs, Holly
Faerber, Austin
Tarr, Phillip I.
Davidson, Nicholas O.
Maternal obesogenic diet enhances cholestatic liver disease in offspring
title Maternal obesogenic diet enhances cholestatic liver disease in offspring
title_full Maternal obesogenic diet enhances cholestatic liver disease in offspring
title_fullStr Maternal obesogenic diet enhances cholestatic liver disease in offspring
title_full_unstemmed Maternal obesogenic diet enhances cholestatic liver disease in offspring
title_short Maternal obesogenic diet enhances cholestatic liver disease in offspring
title_sort maternal obesogenic diet enhances cholestatic liver disease in offspring
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046959/
https://www.ncbi.nlm.nih.gov/pubmed/35341737
http://dx.doi.org/10.1016/j.jlr.2022.100205
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