Division of Integrative Physiology, Kansai Electric Power Medical Research Institute, Kyoto 604-8436, Japan.
Department of Diabetes, Endocrinology and Metabolism/Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Nutrients. 2022 Jul 29;14(15):3117. doi: 10.3390/nu14153117.
d-allulose, a rare sugar, has sweetness with few calories. d-allulose regulates feeding and glycemia, and ameliorates hyperphagia, obesity and diabetes. All these functions involve the central nervous system. However, central mechanisms underlying these effects of d-allulose remain unknown. We recently reported that d-allulose activates the anorexigenic neurons in the hypothalamic arcuate nucleus (ARC), the neurons that respond to glucagon-like peptide-1 and that express proopiomelanocortin. However, its action on the orexigenic neurons remains unknown. This study investigated the effects of d-allulose on the ARC neurons implicated in hunger, by measuring cytosolic Ca concentration ([Ca]) in single neurons. d-allulose depressed the increases in [Ca] induced by ghrelin and by low glucose in ARC neurons and inhibited spontaneous oscillatory [Ca] increases in neuropeptide Y (NPY) neurons. d-allulose inhibited 10 of 35 (28%) ghrelin-responsive, 18 of 60 (30%) glucose-sensitive and 3 of 8 (37.5%) NPY neurons in ARC. Intracerebroventricular injection of d-allulose inhibited food intake at 20:00 and 22:00, the early dark phase when hunger is promoted. These results indicate that d-allulose suppresses hunger-associated feeding and inhibits hunger-promoting neurons in ARC. These central actions of d-allulose represent the potential of d-allulose to inhibit the hyperphagia with excessive appetite, thereby counteracting obesity and diabetes.
d-阿洛酮糖是一种稀有糖，甜度高但热量低。d-阿洛酮糖可以调节摄食和血糖水平，并改善过度摄食、肥胖和糖尿病。所有这些功能都涉及中枢神经系统。然而，d-阿洛酮糖发挥这些作用的中枢机制尚不清楚。我们最近报道，d-阿洛酮糖激活了下丘脑弓状核（ARC）中的厌食神经元，这些神经元对胰高血糖素样肽-1有反应，并表达前阿黑皮素原。然而，其对食欲神经元的作用尚不清楚。本研究通过测量单个神经元胞质钙离子浓度([Ca])，研究了 d-阿洛酮糖对参与饥饿的 ARC 神经元的影响。d-阿洛酮糖抑制了 ghrelin 和低葡萄糖诱导的 ARC 神经元[Ca]的增加，并抑制了神经肽 Y（NPY）神经元中自发振荡的[Ca]增加。d-阿洛酮糖抑制了 ARC 中 35 个（28%）ghrelin 反应性神经元中的 10 个、60 个（30%）葡萄糖敏感性神经元中的 18 个和 8 个（37.5%）NPY 神经元中的 3 个。脑室注射 d-阿洛酮糖抑制了 20:00 和 22:00 时的摄食，这是饥饿增加的早期暗期。这些结果表明，d-阿洛酮糖抑制了与饥饿相关的摄食，并抑制了 ARC 中的饥饿促进神经元。d-阿洛酮糖的这些中枢作用表明它有潜力抑制食欲过盛的过度摄食，从而对抗肥胖和糖尿病。
