Wang Lei, Han Wanxin, Iwasaki Yusaku, Yermek Rakhat, Sharp Geoffrey W G, Seino Yutaka, Yada Toshihiko
Center for Integrative Physiology, Division of Integrative Physiology, Kansai Electric Power Medical Research Institute, 1-5-6 Minatojimaminamimachi, Chuou-ku, Kobe 650-0047, Japan; Division of Diabetes, Metabolism and Endocrinology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-Cho, Chuo-Ku, Kobe 650-0017, Japan.
Laboratory of Animal Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Hangi-cho, Shimogamo, Sakyo-ku, Kyoto 606-8522, Japan.
Neuropeptides. 2021 Oct;89:102180. doi: 10.1016/j.npep.2021.102180. Epub 2021 Jul 10.
Appetite loss or anorexia substantially decreases the quality of life in patients with cancer, depression and gastrointestinal disorders, and can lead to sarcopenia and frailty. Foods that restore appetite have been sought-for but are not currently available. Historically, onion intake was adopted to treat a variety of diseases with reduced appetite including cancer and gastrointestinal disturbances. While isoalliin is a core component of onion, the effects of isoalliin on feeding behavior and feeding centers remain unknown. Neuropeptide Y (NPY) and ghrelin are the most potent central and peripheral inducers of appetite. A Japanese kampo medicine Ninjin'yoeito activates ghrelin-responsive NPY neurons in the hypothalamic arcuate nucleus (ARC) and counteracts anorexia induced by an anti-cancer drug cisplatin. This study explored the effects of isoalliin on feeding behavior and activities of ARC neurons in mice. Isoalliin, injected intraperitoneally, dose-dependently increased food intake during dark phase (DP) and daily without altering light phase (LP) food intake. We measured cytosolic Ca concentration ([Ca]) in single ARC neurons including NPY neurons identified by GFP fluorescence. Isoalliin increased [Ca] in 10 of 18 (55.6%) NPY neurons, a majority of which also responded to ghrelin with [Ca] increases, indicating that the ARC ghrelin-responsive NPY neuron is the major target of isoalliin. Isoalliin also increased [Ca] in the ARC neurons that responded to Ninjin'yoeito. These results indicate that isoalliin enhances feeding at the active period and activates ARC ghrelin-responsive NPY neurons and Ninjin'yoeito-responsive neurons. These abilities of isoalliin to stimulate DP feeding and activate ARC orexigenic neurons provide scientific evidence for the health beneficial effects of onion experienced historically and globally.
食欲减退或厌食会显著降低癌症、抑郁症和胃肠道疾病患者的生活质量，并可能导致肌肉减少症和身体虚弱。人们一直在寻找能恢复食欲的食物，但目前尚未找到。从历史上看，食用洋葱被用于治疗包括癌症和胃肠道紊乱在内的多种食欲减退疾病。虽然异蒜氨酸是洋葱的核心成分，但其对进食行为和进食中枢的影响尚不清楚。神经肽Y（NPY）和胃饥饿素是最有效的中枢和外周食欲诱导剂。一种日本汉方药物人参养荣汤可激活下丘脑弓状核（ARC）中对胃饥饿素敏感的NPY神经元，并抵消抗癌药物顺铂诱导的厌食。本研究探讨了异蒜氨酸对小鼠进食行为和ARC神经元活动的影响。腹腔注射异蒜氨酸，在暗期（DP）和全天均剂量依赖性地增加食物摄入量，而不改变明期（LP）的食物摄入量。我们测量了单个ARC神经元中的细胞溶质钙浓度（[Ca]），其中包括通过绿色荧光蛋白（GFP）荧光鉴定的NPY神经元。异蒜氨酸使18个NPY神经元中的10个（55.6%）[Ca]升高，其中大多数对胃饥饿素也有[Ca]升高反应，表明ARC中对胃饥饿素敏感的NPY神经元是异蒜氨酸的主要作用靶点。异蒜氨酸还使对人参养荣汤有反应的ARC神经元中的[Ca]升高。这些结果表明，异蒜氨酸在活跃期增强进食，并激活ARC中对胃饥饿素敏感的NPY神经元和对人参养荣汤有反应的神经元。异蒜氨酸刺激DP进食和激活ARC促食欲神经元的这些能力为洋葱在历史上和全球范围内所具有的有益健康作用提供了科学证据。
