Restoring polyamine levels by supplementation of spermidine modulates hepatic immune landscape in murine model of NASH
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved..
AIMS: To determine if changes in polyamines metabolism occur during non-alcoholic steatohepatitis (NASH) in human patients and mice, as well as to assess systemic and liver-specific effects of spermidine administration into mice suffering from advanced NASH.
MATERIALS AND METHODS: Human fecal samples were collected from 50 healthy and 50 NASH patients. For the preclinical studies C57Bl6/N male mice fed GAN or NIH-31 diet for 6 months were ordered from Taconic and liver biopsy was performed. Based on severity of liver fibrosis, body composition and body weight, the mice from both dietary groups were randomized into another two groups: half receiving 3 mM spermidine in drinking water, half normal water for subsequent 12 weeks. Body weight was measured weekly and glucose tolerance and body composition were assessed at the end. Blood and organs were collected during necropsy, and intrahepatic immune cells were isolated for flow cytometry analysis.
RESULTS: Metabolomic analysis of human and murine feces confirmed that levels of polyamines decreased along NASH progression. Administration of exogenous spermidine to the mice from both dietary groups did not affect body weight, body composition or adiposity. Moreover, incidence of macroscopic hepatic lesions was higher in NASH mice receiving spermidine. On the other hand, spermidine normalized numbers of Kupffer cells in the livers of mice suffering from NASH, although these beneficial effects did not translate into improved liver steatosis or fibrosis severity.
CONCLUSION: Levels of polyamines decrease during NASH in mice and human patients but spermidine administration does not improve advanced NASH.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1869 |
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| Enthalten in: |
Biochimica et biophysica acta. Molecular basis of disease - 1869(2023), 6 vom: 01. Aug., Seite 166697 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Szydlowska, Marta [VerfasserIn] |
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| Links: |
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| Themen: |
Hepatitis |
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| Anmerkungen: |
Date Completed 05.06.2023 Date Revised 06.06.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbadis.2023.166697 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM355593408 |
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| 245 | 1 | 0 | |a Restoring polyamine levels by supplementation of spermidine modulates hepatic immune landscape in murine model of NASH |
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| 500 | |a Date Revised 06.06.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a AIMS: To determine if changes in polyamines metabolism occur during non-alcoholic steatohepatitis (NASH) in human patients and mice, as well as to assess systemic and liver-specific effects of spermidine administration into mice suffering from advanced NASH | ||
| 520 | |a MATERIALS AND METHODS: Human fecal samples were collected from 50 healthy and 50 NASH patients. For the preclinical studies C57Bl6/N male mice fed GAN or NIH-31 diet for 6 months were ordered from Taconic and liver biopsy was performed. Based on severity of liver fibrosis, body composition and body weight, the mice from both dietary groups were randomized into another two groups: half receiving 3 mM spermidine in drinking water, half normal water for subsequent 12 weeks. Body weight was measured weekly and glucose tolerance and body composition were assessed at the end. Blood and organs were collected during necropsy, and intrahepatic immune cells were isolated for flow cytometry analysis | ||
| 520 | |a RESULTS: Metabolomic analysis of human and murine feces confirmed that levels of polyamines decreased along NASH progression. Administration of exogenous spermidine to the mice from both dietary groups did not affect body weight, body composition or adiposity. Moreover, incidence of macroscopic hepatic lesions was higher in NASH mice receiving spermidine. On the other hand, spermidine normalized numbers of Kupffer cells in the livers of mice suffering from NASH, although these beneficial effects did not translate into improved liver steatosis or fibrosis severity | ||
| 520 | |a CONCLUSION: Levels of polyamines decrease during NASH in mice and human patients but spermidine administration does not improve advanced NASH | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Hepatitis | |
| 650 | 4 | |a Liver | |
| 650 | 4 | |a NAFLD | |
| 650 | 4 | |a NASH | |
| 650 | 4 | |a Polyamines | |
| 650 | 4 | |a Spermidine | |
| 650 | 7 | |a Spermidine |2 NLM | |
| 650 | 7 | |a U87FK77H25 |2 NLM | |
| 650 | 7 | |a Polyamines |2 NLM | |
| 700 | 1 | |a Lasky, Ginger |e verfasserin |4 aut | |
| 700 | 1 | |a Oldham, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Rivera, Cristian |e verfasserin |4 aut | |
| 700 | 1 | |a Ford, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Sellman, Bret R |e verfasserin |4 aut | |
| 700 | 1 | |a Rhodes, Christopher J |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, Taylor S |e verfasserin |4 aut | |
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