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2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans
High levels of 2-hydroxyisobutyric acid (2-HIBA) were found in urines of patients with obesity and hepatic steatosis, suggesting a potential involvement of this metabolite in clinical conditions. The gut microbial origin of 2-HIBA was hypothesized, however its actual origin and role in biological pr...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9749906/ https://www.ncbi.nlm.nih.gov/pubmed/36533081 http://dx.doi.org/10.3389/fmolb.2022.986022 |
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author | Schifano, Emily Conta, Giorgia Preziosi, Adele Ferrante, Carino Batignani, Giovanni Mancini, Patrizia Tomassini, Alberta Sciubba, Fabio Scopigno, Tullio Uccelletti, Daniela Miccheli, Alfredo |
author_facet | Schifano, Emily Conta, Giorgia Preziosi, Adele Ferrante, Carino Batignani, Giovanni Mancini, Patrizia Tomassini, Alberta Sciubba, Fabio Scopigno, Tullio Uccelletti, Daniela Miccheli, Alfredo |
author_sort | Schifano, Emily |
collection | PubMed |
description | High levels of 2-hydroxyisobutyric acid (2-HIBA) were found in urines of patients with obesity and hepatic steatosis, suggesting a potential involvement of this metabolite in clinical conditions. The gut microbial origin of 2-HIBA was hypothesized, however its actual origin and role in biological processes are still not clear. We investigated how treatment with 2-HIBA affected the physiology of the model organism Caenorhabditis elegans, in both standard and high-glucose diet (HGD) growth conditions, by targeted transcriptomic and metabolomic analyses, Coherent Anti-Stokes Raman Scattering (CARS) and two-photon fluorescence microscopy. In standard conditions, 2-HIBA resulted particularly effective to extend the lifespan, delay ageing processes and stimulate the oxidative stress resistance in wild type nematodes through the activation of insulin/IGF-1 signaling (IIS) and p38 MAPK pathways and, consequently, through a reduction of ROS levels. Moreover, variations of lipid accumulation observed in treated worms correlated with transcriptional levels of fatty acid synthesis genes and with the involvement of peptide transporter PEP-2. In HGD conditions, the effect of 2-HIBA on C. elegans resulted in a reduction of the lipid droplets deposition, accordingly with an increase of acs-2 gene transcription, involved in β-oxidation processes. In addition, the pro-longevity effect appeared to be correlated to higher levels of tryptophan, which may play a role in restoring the decreased viability observed in the HGD untreated nematodes. |
format | Online Article Text |
id | pubmed-9749906 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97499062022-12-15 2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans Schifano, Emily Conta, Giorgia Preziosi, Adele Ferrante, Carino Batignani, Giovanni Mancini, Patrizia Tomassini, Alberta Sciubba, Fabio Scopigno, Tullio Uccelletti, Daniela Miccheli, Alfredo Front Mol Biosci Molecular Biosciences High levels of 2-hydroxyisobutyric acid (2-HIBA) were found in urines of patients with obesity and hepatic steatosis, suggesting a potential involvement of this metabolite in clinical conditions. The gut microbial origin of 2-HIBA was hypothesized, however its actual origin and role in biological processes are still not clear. We investigated how treatment with 2-HIBA affected the physiology of the model organism Caenorhabditis elegans, in both standard and high-glucose diet (HGD) growth conditions, by targeted transcriptomic and metabolomic analyses, Coherent Anti-Stokes Raman Scattering (CARS) and two-photon fluorescence microscopy. In standard conditions, 2-HIBA resulted particularly effective to extend the lifespan, delay ageing processes and stimulate the oxidative stress resistance in wild type nematodes through the activation of insulin/IGF-1 signaling (IIS) and p38 MAPK pathways and, consequently, through a reduction of ROS levels. Moreover, variations of lipid accumulation observed in treated worms correlated with transcriptional levels of fatty acid synthesis genes and with the involvement of peptide transporter PEP-2. In HGD conditions, the effect of 2-HIBA on C. elegans resulted in a reduction of the lipid droplets deposition, accordingly with an increase of acs-2 gene transcription, involved in β-oxidation processes. In addition, the pro-longevity effect appeared to be correlated to higher levels of tryptophan, which may play a role in restoring the decreased viability observed in the HGD untreated nematodes. Frontiers Media S.A. 2022-11-23 /pmc/articles/PMC9749906/ /pubmed/36533081 http://dx.doi.org/10.3389/fmolb.2022.986022 Text en Copyright © 2022 Schifano, Conta, Preziosi, Ferrante, Batignani, Mancini, Tomassini, Sciubba, Scopigno, Uccelletti and Miccheli. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Schifano, Emily Conta, Giorgia Preziosi, Adele Ferrante, Carino Batignani, Giovanni Mancini, Patrizia Tomassini, Alberta Sciubba, Fabio Scopigno, Tullio Uccelletti, Daniela Miccheli, Alfredo 2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans |
title | 2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans
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title_full | 2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans
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title_fullStr | 2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans
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title_full_unstemmed | 2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans
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title_short | 2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans
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title_sort | 2-hydroxyisobutyric acid (2-hiba) modulates ageing and fat deposition in caenorhabditis elegans |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9749906/ https://www.ncbi.nlm.nih.gov/pubmed/36533081 http://dx.doi.org/10.3389/fmolb.2022.986022 |
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