Exposure to Artificial Sweetener in Juvenile Mice Intensifies Addictionto High-Fat Diet and Exaggerates Leptin Resistance in Adulthood

幼年期的人工甜味剂可能通过增加下丘脑的内质网应激而增加成年后饮食诱导的肥胖的易感性。这一点得到了化学伴侣和人工甜味剂联合给药的证实，这种甜味剂可以减轻成年后下丘脑ER应激和HFD偏好。在小鼠原代神经细胞中，人工甜味剂显著增强了内质网应激相关基因的表达，表明人工甜味剂对下丘脑内质网应激有直接贡献。

Artificial sweeteners during the juvenile period may increase susceptibility to diet-induced obesity in adulthood through the augmentation of ER stress in the hypothalamus. This was confirmed by co-administration of a chemical chaperone with artificial sweeteners, which attenuated hypothalamic ER stress and HFD preference in adulthood. In murine primary neuronal cells, artificial sweeteners substantially augmented the expression of ER stress-related genes, suggesting direct contribution of artificial sweeteners to hypothalamic ER stress.