Rodrigues Thyago de Oliveira, Dos Santos Júnior Osmar Henrique, Beltrão de Lemos Maria Daniele Teixeira, de Sousa Fernandes Matheus Santos, Yagin Fatma Hilal, Yagin Burak, Das Samarjit, Alghannam Abdullah F, Prieto-González Pablo, Lagranha Claudia J
Graduate Program in Nutrition, Physical Activity and Phenotypic Plasticity, Academic Center of Vitória, UFPE - CAV, Federal University of Pernambuco, Recife, Brazil.
Graduate Program in Neuropsychiatry and Behavioral Sciences, Federal University of Pernambuco, Recife, Brazil.
Front Mol Biosci. 2025 May 16;12:1564061. doi: 10.3389/fmolb.2025.1564061. eCollection 2025.
Obesity is a global epidemic identified by the World Health Organization, and its complexity involves genetic, cultural, socioeconomic, and behavioral factors.
In this study, we used female Wistar rats, with litters standardized to nine female pups, which were divided into two groups: normally nourished or overnourished. The groups were further subdivided into control and fluoxetine-treated groups, with the pharmacological treatment maintained until the 21st day of life. At 30 days of age, euthanasia was performed, and tissues from the hypothalamus and brainstem were collected.
We observed an increase in body weight and the Lee index in the overnourished group, but fluoxetine treatment reduced these indices. Additionally, overnourished rats consumed more palatable food. Biochemically, NADH content in the hypothalamus was altered by overnutrition but restored by fluoxetine treatment. Citrate synthase activity was reduced in the overnourished group in the hypothalamus but increased in the brainstem of fluoxetine-treated rats. The production of reactive oxygen species was higher in the overnourished group, and oxidative stress biomarkers showed increased levels of MDA and protein carbonylation in these rats. Overnutrition impaired the antioxidant activity of enzymes in both the hypothalamus and brainstem, whereas fluoxetine treatment improved this activity. BDNF expression was higher in the fluoxetine-treated groups compared to the overnourished group.
These results demonstrate the detrimental effects of maternal overnutrition on the development of female offspring and the therapeutic potential of serotonergic manipulation to mitigate the early effects of obesity, with tissue-specific variations.
肥胖是世界卫生组织确认的一种全球流行病，其复杂性涉及遗传、文化、社会经济和行为因素。
在本研究中，我们使用雌性Wistar大鼠，将其幼崽标准化为9只雌性幼崽，并分为两组：正常营养组或营养过剩组。这些组进一步细分为对照组和氟西汀治疗组，药物治疗持续至出生后第21天。在30日龄时实施安乐死，并收集下丘脑和脑干组织。
我们观察到营养过剩组的体重和李氏指数增加，但氟西汀治疗降低了这些指标。此外，营养过剩的大鼠食用了更多美味食物。在生物化学方面，下丘脑的NADH含量因营养过剩而改变，但经氟西汀治疗后恢复。下丘脑营养过剩组的柠檬酸合酶活性降低，但氟西汀治疗的大鼠脑干中的柠檬酸合酶活性增加。营养过剩组的活性氧产生较高，氧化应激生物标志物显示这些大鼠的丙二醛和蛋白质羰基化水平升高。营养过剩损害了下丘脑和脑干中酶的抗氧化活性，而氟西汀治疗改善了这种活性。与营养过剩组相比，氟西汀治疗组的脑源性神经营养因子表达更高。
这些结果证明了母体营养过剩对雌性后代发育产生的有害影响，以及血清素调节对减轻肥胖早期影响的治疗潜力，且存在组织特异性差异。
