Plummer Jason D, Johnson Jay E
Department of Biology, Orentreich Foundation for the Advancement of Science, Cold Spring, NY, USA.
J Inflamm (Lond). 2025 Jun 19;22(1):24. doi: 10.1186/s12950-025-00451-z.
Dietary methionine restriction (MR) produces multiple metabolic health benefits and extends the healthspan of several model organisms, including rodents. MR is feasible for humans, and studies have reported that methionine-restricted human subjects receive similar benefits to rodents. However, long-term adherence to continuous MR is likely to be challenging (if not impossible) for many individuals. Another obstacle to the successful translation of this intervention is the fact that multiple deleterious effects of continuous MR have been reported for mice and humans, including loss of musculoskeletal mass, increased bone marrow adipogenesis, and an increased incidence of fractures. To address these issues, we developed two novel interventions that produce similar health benefits to continuous MR, but without the same deleterious side effects. The first is an intermittent form of MR (IMR) that requires only 3 days of reduced methionine intake per week; the second involves supplementation of an otherwise normal diet with sodium selenite. For the current study, we considered the possibility that these interventions might also prevent and/or ameliorate diet-induced chronic inflammation, as well as pathologies that result from this condition. Accordingly, we tested whether IMR or selenium supplementation were able to protect high-fat diet-fed mice against both inflammation and the development of inflammation-induced ulcerative dermatitis. Here, we show that high-fat diet-fed mice undergoing both interventions not only have relatively low levels of inflammation, but are also protected against the development of dermatitis. We also propose a model for the mechanistic basis of such benefits, which involves reduced activation of leptin-responsive pro-inflammatory pathways.
The online version contains supplementary material available at 10.1186/s12950-025-00451-z.
饮食中蛋氨酸限制（MR）可带来多种代谢健康益处，并延长包括啮齿动物在内的多种模式生物的健康寿命。MR对人类而言是可行的，且研究报告称，接受蛋氨酸限制的人类受试者获得了与啮齿动物类似的益处。然而，长期坚持持续的MR对许多人来说可能具有挑战性（甚至不可能）。这种干预措施成功转化应用的另一个障碍是，已报道持续MR对小鼠和人类存在多种有害影响，包括肌肉骨骼质量损失、骨髓脂肪生成增加以及骨折发生率上升。为解决这些问题，我们开发了两种新型干预措施，它们能产生与持续MR类似的健康益处，但没有相同的有害副作用。第一种是间歇性MR（IMR），每周仅需3天减少蛋氨酸摄入量；第二种是在正常饮食中添加亚硒酸钠。在当前研究中，我们考虑了这些干预措施是否也能预防和/或改善饮食诱导的慢性炎症以及由此引发的病理状况。因此，我们测试了IMR或补充硒是否能够保护高脂饮食喂养的小鼠免受炎症以及炎症诱导的溃疡性皮肤病的发生。在此，我们表明接受这两种干预措施的高脂饮食喂养小鼠不仅炎症水平相对较低，而且还能预防皮炎的发生。我们还提出了一个关于此类益处的机制基础的模型，该模型涉及瘦素反应性促炎途径的激活减少。
在线版本包含可在10.1186/s12950 - 025 - 00451 - z获取的补充材料。
