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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.986022/full |
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| author | Emily Schifano Giorgia Conta Giorgia Conta Adele Preziosi Carino Ferrante Carino Ferrante Giovanni Batignani Giovanni Batignani Patrizia Mancini Alberta Tomassini Alberta Tomassini Fabio Sciubba Fabio Sciubba Tullio Scopigno Tullio Scopigno Daniela Uccelletti Alfredo Miccheli Alfredo Miccheli |
| author_facet | Emily Schifano Giorgia Conta Giorgia Conta Adele Preziosi Carino Ferrante Carino Ferrante Giovanni Batignani Giovanni Batignani Patrizia Mancini Alberta Tomassini Alberta Tomassini Fabio Sciubba Fabio Sciubba Tullio Scopigno Tullio Scopigno Daniela Uccelletti Alfredo Miccheli Alfredo Miccheli |
| author_sort | Emily Schifano |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T05:54:25Z |
| format | Article |
| id | doaj.art-d94e00c9ef41443590da8c97f43f8484 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-12T05:54:25Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-d94e00c9ef41443590da8c97f43f84842022-12-22T03:45:12ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-11-01910.3389/fmolb.2022.9860229860222-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegansEmily Schifano0Giorgia Conta1Giorgia Conta2Adele Preziosi3Carino Ferrante4Carino Ferrante5Giovanni Batignani6Giovanni Batignani7Patrizia Mancini8Alberta Tomassini9Alberta Tomassini10Fabio Sciubba11Fabio Sciubba12Tullio Scopigno13Tullio Scopigno14Daniela Uccelletti15Alfredo Miccheli16Alfredo Miccheli17Department of Biology and Biotechnology “C. Darwin”, Sapienza University of Rome, Rome, ItalyDepartment of Environmental Biology, Sapienza University of Rome, Rome, ItalyNMR-based Metabolomics Laboratory of Sapienza (NMLab), Sapienza University of Rome, Rome, ItalyDepartment of Biology and Biotechnology “C. Darwin”, Sapienza University of Rome, Rome, ItalyDepartment of Physics, Sapienza University of Rome, Rome, ItalyCenter for Life Nano- and Neuro-science, Istituto Italiano di Tecnologia, Rome, ItalyDepartment of Physics, Sapienza University of Rome, Rome, ItalyCenter for Life Nano- and Neuro-science, Istituto Italiano di Tecnologia, Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Environmental Biology, Sapienza University of Rome, Rome, ItalyNMR-based Metabolomics Laboratory of Sapienza (NMLab), Sapienza University of Rome, Rome, ItalyDepartment of Environmental Biology, Sapienza University of Rome, Rome, ItalyNMR-based Metabolomics Laboratory of Sapienza (NMLab), Sapienza University of Rome, Rome, ItalyDepartment of Physics, Sapienza University of Rome, Rome, ItalyCenter for Life Nano- and Neuro-science, Istituto Italiano di Tecnologia, Rome, ItalyDepartment of Biology and Biotechnology “C. Darwin”, Sapienza University of Rome, Rome, ItalyDepartment of Environmental Biology, Sapienza University of Rome, Rome, ItalyNMR-based Metabolomics Laboratory of Sapienza (NMLab), Sapienza University of Rome, Rome, ItalyHigh 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.https://www.frontiersin.org/articles/10.3389/fmolb.2022.986022/full2-hydroxyisobutyric acidCaenorhabditis elegansageinglipid metabolismoxidative stresshigh-glucose diet |
| spellingShingle | Emily Schifano Giorgia Conta Giorgia Conta Adele Preziosi Carino Ferrante Carino Ferrante Giovanni Batignani Giovanni Batignani Patrizia Mancini Alberta Tomassini Alberta Tomassini Fabio Sciubba Fabio Sciubba Tullio Scopigno Tullio Scopigno Daniela Uccelletti Alfredo Miccheli Alfredo Miccheli 2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans Frontiers in Molecular Biosciences 2-hydroxyisobutyric acid Caenorhabditis elegans ageing lipid metabolism oxidative stress high-glucose diet |
| 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 | 2-hydroxyisobutyric acid Caenorhabditis elegans ageing lipid metabolism oxidative stress high-glucose diet |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.986022/full |
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