Effects of Individual Amino Acids on PPARα Transactivation, mTORC1 Activation, ApoA-I Transcription and pro-ApoA-I Secretion.

Abstract

A higher concentration of apolipoprotein A-I (ApoA-I) is associated with increased high density lipoprotein functionality and reverse cholesterol transport (RCT). A promising strategy to prevent cardiovascular diseases is therefore to improve RCT by increasing de novo ApoA-I production. Since experimental animal models have suggested effects of amino acids on hepatic lipoprotein metabolism, we here examined the effects of different amino acids on hepatic ApoA-I production. Human hepatocytes (HepG2) were exposed to six individual amino acids for 48 h. ApoA-I transcription and secreted pro-ApoA-I protein concentrations were analyzed using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assays (ELISA), respectively. Additionally, CPT1 and KEAP1 mRNA expression, peroxisome proliferator-activated receptor alpha (PPARα) transactivation, and mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation were determined. Leucine, glutamic acid, and tryptophan increased ApoA-I and CPT1 mRNA expression. Tryptophan also strongly increased PPARα transactivation. Glutamine, proline, and histidine increased pro-ApoA-I protein concentrations but mTORC1 phosphorylation remained unchanged regardless of the amino acid provided. In conclusion, individual amino acids have different effects on ApoA-I mRNA expression and pro-ApoA-I production which can partially be explained by specific effects on PPARα transactivation, while mTORC1 phosphorylation remained unaffected.

• Authors: Jehad Z Tayyeb, Herman E Popeijus, Janna van de Sanden, Willem Zwaan, Ronald P Mensink, Jogchum Plat
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 11 (May 28 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35682748 (Publication Type: Journal Article)

Chemical References

• Amino Acids
• Apolipoprotein A-I
• PPAR alpha
• RNA, Messenger
• Tryptophan
• Mechanistic Target of Rapamycin Complex 1

Topics

• Amino Acids (metabolism)
• Animals
• Apolipoprotein A-I (genetics, metabolism)
• Mechanistic Target of Rapamycin Complex 1 (metabolism)
• PPAR alpha (genetics, metabolism)
• RNA, Messenger (genetics)
• Transcriptional Activation
• Tryptophan (metabolism)