Short-Chain Fatty Acids (Except Hexanoic Acid) Lower NF-kB Transactivation, Which Rescues Inflammation-Induced Decreased Apolipoprotein A-I Transcription in HepG2 Cells
Concentrations of apolipoprotein A-I (ApoA-I) decrease during inflammation, which may lead to dysfunctional ApoA-I-poor high-density lipoprotein (HDL) particles, and as such, elevate cardiovascular risk. Therefore, rescuing ApoA-I concentrations, especially during inflammation, seems beneficial. Rec...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/14/5088 |
| _version_ | 1797562020224040960 |
|---|---|
| author | Jehad Z. Tayyeb Herman E. Popeijus Ronald P. Mensink Maurice C. J. M. Konings Fatma B. A. Mokhtar Jogchum Plat |
| author_facet | Jehad Z. Tayyeb Herman E. Popeijus Ronald P. Mensink Maurice C. J. M. Konings Fatma B. A. Mokhtar Jogchum Plat |
| author_sort | Jehad Z. Tayyeb |
| collection | DOAJ |
| description | Concentrations of apolipoprotein A-I (ApoA-I) decrease during inflammation, which may lead to dysfunctional ApoA-I-poor high-density lipoprotein (HDL) particles, and as such, elevate cardiovascular risk. Therefore, rescuing ApoA-I concentrations, especially during inflammation, seems beneficial. Recently, short-chain fatty acids (SCFAs) have received more attention as a strategy in reversing atherosclerosis. We here evaluated the effects of SCFAs on inflammatory pathways in relation to ApoA-I transcription. SCFAs dose–response studies were performed in the presence and absence of inflammatory cytokines. ApoA-I and interleukin 8 (IL-8) mRNA expression were analyzed using qPCR and ELISA, respectively. To study underlying mechanisms, nuclear factor kappa B (NF-κB) transactivation and changes in mRNA expressions of the genes targets of bromodomain and extra-terminal (BET) inhibition, peroxisome proliferator-activated receptor-alpha (PPARα) transactivation and activator protein 1 (AP-1) pathway were analyzed. SCFAs (except hexanoic acid) increased ApoA-I mRNA transcription in both normal and inflammatory conditions and lowered IL-8 mRNA expression. This anti-inflammatory effect of SCFAs was confirmed by inhibition of NF-κB transactivation. Moreover, butyric acid increased carnitine palmitoyltransferase 1 (CPT1), PPARα target gene, mRNA transcription in both conditions, and there was a negative correlation between CPT1 and NF-κB. Therefore, PPARα transactivation is probably involved in the anti-inflammatory effects of SCFAs, which rescues ApoA-I transcription. In conclusion, propionate, butyrate and valerate elicit anti-inflammatory effects which might rescue ApoA-I transcription in inflammatory conditions via PPARα transactivation mediated NF-κB inhibition. |
| first_indexed | 2024-03-10T18:22:44Z |
| format | Article |
| id | doaj.art-63d1bcbb5a6642888783dd14d8e727ca |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:22:44Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-63d1bcbb5a6642888783dd14d8e727ca2023-11-20T07:13:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114508810.3390/ijms21145088Short-Chain Fatty Acids (Except Hexanoic Acid) Lower NF-kB Transactivation, Which Rescues Inflammation-Induced Decreased Apolipoprotein A-I Transcription in HepG2 CellsJehad Z. Tayyeb0Herman E. Popeijus1Ronald P. Mensink2Maurice C. J. M. Konings3Fatma B. A. Mokhtar4Jogchum Plat5Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ET Maastricht, The NetherlandsDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ET Maastricht, The NetherlandsDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ET Maastricht, The NetherlandsDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ET Maastricht, The NetherlandsDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ET Maastricht, The NetherlandsDepartment of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ET Maastricht, The NetherlandsConcentrations of apolipoprotein A-I (ApoA-I) decrease during inflammation, which may lead to dysfunctional ApoA-I-poor high-density lipoprotein (HDL) particles, and as such, elevate cardiovascular risk. Therefore, rescuing ApoA-I concentrations, especially during inflammation, seems beneficial. Recently, short-chain fatty acids (SCFAs) have received more attention as a strategy in reversing atherosclerosis. We here evaluated the effects of SCFAs on inflammatory pathways in relation to ApoA-I transcription. SCFAs dose–response studies were performed in the presence and absence of inflammatory cytokines. ApoA-I and interleukin 8 (IL-8) mRNA expression were analyzed using qPCR and ELISA, respectively. To study underlying mechanisms, nuclear factor kappa B (NF-κB) transactivation and changes in mRNA expressions of the genes targets of bromodomain and extra-terminal (BET) inhibition, peroxisome proliferator-activated receptor-alpha (PPARα) transactivation and activator protein 1 (AP-1) pathway were analyzed. SCFAs (except hexanoic acid) increased ApoA-I mRNA transcription in both normal and inflammatory conditions and lowered IL-8 mRNA expression. This anti-inflammatory effect of SCFAs was confirmed by inhibition of NF-κB transactivation. Moreover, butyric acid increased carnitine palmitoyltransferase 1 (CPT1), PPARα target gene, mRNA transcription in both conditions, and there was a negative correlation between CPT1 and NF-κB. Therefore, PPARα transactivation is probably involved in the anti-inflammatory effects of SCFAs, which rescues ApoA-I transcription. In conclusion, propionate, butyrate and valerate elicit anti-inflammatory effects which might rescue ApoA-I transcription in inflammatory conditions via PPARα transactivation mediated NF-κB inhibition.https://www.mdpi.com/1422-0067/21/14/5088ApoA-IinflammationNF-κBPPARαSCFAs |
| spellingShingle | Jehad Z. Tayyeb Herman E. Popeijus Ronald P. Mensink Maurice C. J. M. Konings Fatma B. A. Mokhtar Jogchum Plat Short-Chain Fatty Acids (Except Hexanoic Acid) Lower NF-kB Transactivation, Which Rescues Inflammation-Induced Decreased Apolipoprotein A-I Transcription in HepG2 Cells International Journal of Molecular Sciences ApoA-I inflammation NF-κB PPARα SCFAs |
| title | Short-Chain Fatty Acids (Except Hexanoic Acid) Lower NF-kB Transactivation, Which Rescues Inflammation-Induced Decreased Apolipoprotein A-I Transcription in HepG2 Cells |
| title_full | Short-Chain Fatty Acids (Except Hexanoic Acid) Lower NF-kB Transactivation, Which Rescues Inflammation-Induced Decreased Apolipoprotein A-I Transcription in HepG2 Cells |
| title_fullStr | Short-Chain Fatty Acids (Except Hexanoic Acid) Lower NF-kB Transactivation, Which Rescues Inflammation-Induced Decreased Apolipoprotein A-I Transcription in HepG2 Cells |
| title_full_unstemmed | Short-Chain Fatty Acids (Except Hexanoic Acid) Lower NF-kB Transactivation, Which Rescues Inflammation-Induced Decreased Apolipoprotein A-I Transcription in HepG2 Cells |
| title_short | Short-Chain Fatty Acids (Except Hexanoic Acid) Lower NF-kB Transactivation, Which Rescues Inflammation-Induced Decreased Apolipoprotein A-I Transcription in HepG2 Cells |
| title_sort | short chain fatty acids except hexanoic acid lower nf kb transactivation which rescues inflammation induced decreased apolipoprotein a i transcription in hepg2 cells |
| topic | ApoA-I inflammation NF-κB PPARα SCFAs |
| url | https://www.mdpi.com/1422-0067/21/14/5088 |
| work_keys_str_mv | AT jehadztayyeb shortchainfattyacidsexcepthexanoicacidlowernfkbtransactivationwhichrescuesinflammationinduceddecreasedapolipoproteinaitranscriptioninhepg2cells AT hermanepopeijus shortchainfattyacidsexcepthexanoicacidlowernfkbtransactivationwhichrescuesinflammationinduceddecreasedapolipoproteinaitranscriptioninhepg2cells AT ronaldpmensink shortchainfattyacidsexcepthexanoicacidlowernfkbtransactivationwhichrescuesinflammationinduceddecreasedapolipoproteinaitranscriptioninhepg2cells AT mauricecjmkonings shortchainfattyacidsexcepthexanoicacidlowernfkbtransactivationwhichrescuesinflammationinduceddecreasedapolipoproteinaitranscriptioninhepg2cells AT fatmabamokhtar shortchainfattyacidsexcepthexanoicacidlowernfkbtransactivationwhichrescuesinflammationinduceddecreasedapolipoproteinaitranscriptioninhepg2cells AT jogchumplat shortchainfattyacidsexcepthexanoicacidlowernfkbtransactivationwhichrescuesinflammationinduceddecreasedapolipoproteinaitranscriptioninhepg2cells |