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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...

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Autores principales: Schifano, Emily, Conta, Giorgia, Preziosi, Adele, Ferrante, Carino, Batignani, Giovanni, Mancini, Patrizia, Tomassini, Alberta, Sciubba, Fabio, Scopigno, Tullio, Uccelletti, Daniela, Miccheli, Alfredo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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.
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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
title_full 2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans
title_fullStr 2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans
title_full_unstemmed 2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans
title_short 2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans
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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