Details

Autor(en) / Beteiligte

• Takasawa, Seidai
• Kimura, Kosuke
• Miyanaga, Masato
• Uemura, Takuya
• Hachisu, Masakazu
• Miyagawa, Shinichi
• Ramadan, Abdelaziz
• Sukegawa, Satoru
• Kobayashi, Masaki
• Kimura, Seisuke
• Matsui, Kenji
• Shiroishi, Mitsunori
• Terashita, Kaori
• Nishiyama, Chiharu
• Yashiro, Takuya
• Nagata, Kazuki
• Higami, Yoshikazu
• Arimura, Gen-Ichiro

Titel

The powerful potential of amino acid menthyl esters for anti-inflammatory and anti-obesity therapies

Ist Teil von

• Immunology, 2024-05

Ort / Verlag

England

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.