Short-chain fatty acids (except hexanoic acid) lower NF-kB transactivation, which rescues inflammation-induced decreased apolipoprotein A-I transcription in HepG2 cells
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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.
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SCFAs are associated with a variety of diseases such as rectal cancer, pancreatitis, abnormal energy metabolism, constipation, blood lipid metabolism, sleep disorders and Alzheimer's disease.
“Studies have found that SCFAs are associated with a variety of diseases such as rectal cancer, 174 pancreatitis, 175 abnormal energy metabolism, 176 constipation, 177 blood lipid metabolism, 178 sleep disorders 179 and Alzheimer's disease.180”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [178]
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- Authors
- Tayyeb, J. Z., Popeijus, H. E., Mensink, R. P., Konings, M. C. J. M., Mokhtar, F. B. A., & Plat, J.
- Affiliations
- Maastricht University (NL)
- Corresponding author
- Tayyeb, Jehad Z.
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-07-18
- Volume
- 21
- Issue
- 14
- Pages
- 5088
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7404194
- OpenAlex
- W3043464429
- Cited by
- 74
- References
- 29
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 14 · 2023: 16 · 2022: 11 · 2021: 9 · 2020: 1
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- short-chain fatty acids, apolipoprotein A-I, NF-κB transactivation, inflammation, PPARα, butyrate, propionate, valerate, interleukin-8, carnitine palmitoyltransferase 1, high-density lipoprotein, atherosclerosis, anti-inflammatory activity, hepatocytes
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Butyrates, Caproates, Carnitine O-Palmitoyltransferase, Fatty Acids, Volatile, Humans, Inflammation, Propionates, Valerates, Transcriptional Activation, Interleukin-8, Apolipoprotein A-I, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-fos, I-kappa B Proteins, PPAR alpha, Hep G2 Cells
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