Atopic dermatitis (AD) is a skin disorder that presents with itching and scratching and frequently progresses to a chronic state. AD often develops in patients with an individual or family history of allergic diseases. In addition, AD may develop in patients exposed to environmental stimuli such as air pollutants or dust. However, there can be differences in the magnitude of symptoms between patients even with the same genetic background or exposure to similar environmental conditions. NC/Nga mice have been used as a model for AD. They show AD-like symptoms in an age-dependent manner, even in the absence of AD-inducing agents. In addition, similar to humans, the magnitude of AD symptoms in this model varies between individual mice. However, the mechanisms underlying these differences are unclear. In addition, little is known about the relationship between AD skin symptoms and other organs and tissues. Here, we performed a metabolome analysis on sera from NC/ Nga mice to identify factors potentially related to the severity of AD symptoms. The analysis showed a correlation between reduced serum methionine levels and increased severity of AD. In addition, treatment with excess methionine before the onset of AD symptoms suppressed the development of AD. In contrast, administration of methionine after the onset of AD symptoms did not. Importantly, cysteine and taurine, irreversible metabolites of methionine, did not suppress AD development. These results show that methionine, but not its metabolites, is a key factor in the onset, rather than the development of AD.

Allergic contact dermatitis (ACD) is a common skin disorder caused by contact with allergens.The optimal treatment for ACD is to avoid contact with allergens. However, in some cases, avoiding exposure is not possible when the allergens are unknown. Therefore, establishing treatment methods other than allergen avoidance is important. We previously reported that the continuous administration of methionine, an essential amino acid, in a mouse model of atopic dermatitis alleviated its symptoms. In the present study, we investigated the effect of methionine on a mouse model of ACD caused by 1-fluoro-2,4-dinitrobenzene (DNFB).Differences in the effect of methionine were observed in DNFB-induced ACD model mice based on the mouse strain used. This difference was attributed to the suppression of hepatic dimethylglycine (DMG) production, which is associated with the suppression of hepatic betaine-homocysteine methyltransferase (Bhmt) expression by ACD. Although we did not reveal the mechanism underlying DMG suppression, our study suggests the presence of interactions between the liver and skin in dermatitis, such as the regulation of hepatic metabolic enzyme expression in dermatitis and the alleviation of dermatitis symptoms by the hepatic metabolism status of DMG.