The powerful potential of amino acid menthyl esters for anti-inflammatory and anti-obesity therapies.
TRPM8
amino acid menthyl esters
anti‐inflammatory
anti‐obesity
liver X receptor
Journal
Immunology
ISSN: 1365-2567
Titre abrégé: Immunology
Pays: England
ID NLM: 0374672
Informations de publication
Date de publication:
08 May 2024
08 May 2024
Historique:
received:
05
12
2023
accepted:
17
04
2024
medline:
9
5
2024
pubmed:
9
5
2024
entrez:
9
5
2024
Statut:
aheadofprint
Résumé
Our newly developed menthyl esters of valine and isoleucine exhibit anti-inflammatory properties beyond those of the well-known menthol in macrophages stimulated by lipopolysaccharide (LPS) and in a mouse model of colitis induced by sodium dextran sulfate. Unlike menthol, which acts primarily through the cold-sensitive TRPM8 channel, these menthyl esters displayed unique mechanisms that operate independently of this receptor. They readily penetrated target cells and efficiently suppressed LPS-stimulated tumour necrosis factor-alpha (Tnf) expression mediated by liver X receptor (LXR), a key nuclear receptor that regulates intracellular cholesterol and lipid balance. The menthyl esters showed affinity for LXR and enhanced the transcriptional activity through their non-competitive and potentially synergistic agonistic effect. This effect can be attributed to the crucial involvement of SCD1, an enzyme regulated by LXR, which is central to lipid metabolism and plays a key role in the anti-inflammatory response. In addition, we discovered that the menthyl esters showed remarkable efficacy in suppressing adipogenesis in 3T3-L1 adipocytes at the mitotic clonal expansion stage in an LXR-independent manner as well as in mice subjected to diet-induced obesity. These multiple capabilities of our compounds establish them as formidable allies in the fight against inflammation and obesity, paving the way for a range of potential therapeutic applications.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Tokyo University of Science Research Grants
Organisme : Japan Society for the Promotion of Science
ID : 20H02951
Organisme : Japan Society for the Promotion of Science
ID : 24K01723
Informations de copyright
© 2024 John Wiley & Sons Ltd.
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