Sagae Sara C, Paz Edson D R, Zanardini Bárbara, Amaral Ana Claudia, Bronczek Gabriela A, Koehler-Santos Patrícia, de Oliveira Jarbas R, Franci Celso R, Donadio Márcio V F, Holman Parker J, Raineki Charlis
Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil.
Departamento de Fisiologia Geral do Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
PLoS One. 2025 Mar 3;20(3):e0313103. doi: 10.1371/journal.pone.0313103. eCollection 2025.
The increased risk for obesity and metabolic disorders following early-life adversity is aggravated by poor diet (e.g., cafeteria diet). Alternate-day fasting (ADF) is a dietary regimen shown to improve immune and metabolic dysfunction related to obesity. Here, we evaluate if ADF can ameliorate the negative effects of early-life adversity and/or cafeteria diet on biological, immune and metabolic parameters. At weaning, animals reared under normal or adverse conditions (i.e., low bedding) were fed either standard chow or cafeteria diets ad libitum or subjected to an ADF regimen. In adulthood, we measured 24-hour fasted cholesterol, triglycerides, cytokines, oxidative stress markers, and body composition parameters including perigonadal, retroperitoneal, and brown fat pad weight. Animals exposed to early-life adversity respond differently to cafeteria diet and ADF. Adverse reared animals fed chow diet in the ADF regimen showed the largest reduction in body weight and perigonadal and retroperitoneal fat pad weight, the smallest increase in corticosterone levels, and the largest increase in TNF-α levels. However, the differential effects of the ADF regimen on body, perigonadal and retroperitoneal fat weight observed in adversely reared animals fed chow diet compared to controls were not present if the adversely reared animals were fed cafeteria diet in the ADF regimen. Furthermore, adversely reared animals fed cafeteria diet in the ADF regimen showed high IL-1β and IL-6 levels. Together, the data suggest that the altered vulnerability to metabolic and immune dysfunction following early-life adversity is not just due to the type of diet but also how the diet is consumed.
早年生活逆境后肥胖和代谢紊乱风险的增加会因不良饮食（如自助餐厅饮食）而加剧。隔日禁食（ADF）是一种已被证明可改善与肥胖相关的免疫和代谢功能障碍的饮食方案。在此，我们评估ADF是否能改善早年生活逆境和/或自助餐厅饮食对生物学、免疫和代谢参数的负面影响。在断奶时，将在正常或不良条件（即低垫料）下饲养的动物随意喂食标准饲料或自助餐厅饮食，或采用ADF方案。成年后，我们测量了24小时禁食状态下的胆固醇、甘油三酯、细胞因子、氧化应激标志物以及身体成分参数，包括性腺周围、腹膜后和棕色脂肪垫重量。暴露于早年生活逆境的动物对自助餐厅饮食和ADF的反应不同。在ADF方案中喂食普通饲料的不良饲养动物体重、性腺周围和腹膜后脂肪垫重量下降幅度最大，皮质酮水平升高幅度最小，TNF-α水平升高幅度最大。然而，如果在ADF方案中给不良饲养动物喂食自助餐厅饮食，那么与对照组相比，在喂食普通饲料的不良饲养动物中观察到的ADF方案对身体、性腺周围和腹膜后脂肪重量的差异影响就不存在了。此外，在ADF方案中喂食自助餐厅饮食的不良饲养动物显示出较高的IL-1β和IL-6水平。总之，数据表明，早年生活逆境后对代谢和免疫功能障碍的易感性改变不仅取决于饮食类型，还取决于饮食的摄入方式。
