Aguilar-Lozano Ana, Palacios-González Berenice, Guevara-Cruz Martha, Tovar Armando R, Palma-Guzman Alam, Noriega Lilia G
Department of Nutritional Physiology, National Institute of Medical and Nutritional Sciences "Salvador Zubirán", Mexico City, Mexico.
Biomedical Sciences PhD program, National Autonomous Mexican University (UNAM), Mexico City, Mexico.
PLoS One. 2025 Jan 24;20(1):e0315197. doi: 10.1371/journal.pone.0315197. eCollection 2025.
Childhood obesity increases the risk of developing metabolic diseases in adulthood, since environmental stimuli during critical windows of development can impact on adult metabolic health. Studies demonstrating the effect of prepubertal diet on adult metabolic disease risk are still limited. We hypothesized that a prepubertal control diet (CD) protects the adult metabolic phenotype from diet-induced obesity (DIO), while a high-fat diet (HFD) would predispose to adult metabolic alterations. Sprague-Dawley male rats were fed either a CD or a HFD during the prepubertal period (day 30-40 of age) and subsequently a chronic HFD or CD, respectively, until adulthood (day 220 of age). As controls, rats aged 30 days were exclusively fed a CD or a HFD until adulthood. Body weight and composition, metabolic rate, biochemical and hormonal plasma measurements, hepatic gene expression and methylation and hydroxymethylation levels were analyzed at ages 30, 40 and 220 days. The prepubertal CD prevented fat mass accumulation, lean mass loss and metabolic inflexibility, showed lower insulin, leptin and cholesterol concentrations in adulthood despite the chronic HFD. Notably, the prepubertal CD led to higher hepatic Lxrα expression, lower hepatic global DNA methylation and higher hydroxymethylation in adulthood despite a chronic HFD. Conversely, a prepubertal HFD decreased adult metabolic flexibility, increased serum cholesterol, and decreased Lxrα expression and global DNA hydroxymethylation, while also increasing DNA methylation levels despite a chronic CD. In summary, a prepubertal CD protected the adult metabolic phenotype from high cholesterol concentrations associated with increased hepatic Lxrα expression and lower hepatic global DNA methylation in adulthood, despite exposure to a chronic HFD. Conversely, a prepubertal HFD altered the adult metabolic phenotype.
儿童肥胖会增加成年后患代谢性疾病的风险，因为发育关键期的环境刺激会影响成年后的代谢健康。证明青春期前饮食对成年代谢疾病风险影响的研究仍然有限。我们假设青春期前的对照饮食（CD）可保护成年代谢表型免受饮食诱导的肥胖（DIO）影响，而高脂饮食（HFD）则会使成年后易发生代谢改变。在青春期前阶段（30 - 40日龄），将斯普拉格 - 道利雄性大鼠分别喂食CD或HFD，随后分别喂食慢性HFD或CD，直至成年（220日龄）。作为对照，30日龄的大鼠仅喂食CD或HFD直至成年。在30、40和220日龄时分析体重和组成、代谢率、血浆生化和激素指标、肝脏基因表达以及甲基化和羟甲基化水平。青春期前的CD可防止脂肪量积累、瘦体重减少和代谢灵活性降低，尽管长期喂食HFD，但成年后胰岛素、瘦素和胆固醇浓度较低。值得注意的是，尽管长期喂食HFD，但青春期前的CD导致成年后肝脏Lxrα表达升高、肝脏整体DNA甲基化降低和羟甲基化升高。相反，青春期前的HFD降低了成年后的代谢灵活性，增加了血清胆固醇，降低了Lxrα表达和整体DNA羟甲基化，同时尽管长期喂食CD，DNA甲基化水平也有所增加。总之，青春期前的CD可保护成年代谢表型免受与成年后肝脏Lxrα表达增加和肝脏整体DNA甲基化降低相关的高胆固醇浓度影响，尽管暴露于长期HFD中。相反，青春期前的HFD改变了成年代谢表型。
