Jantsch Jeferson, da Silva Rodrigues Fernanda, Silva Dias Victor, de Farias Fraga Gabriel, Eller Sarah, Giovenardi Márcia, Guedes Renata Padilha
Graduate Program in Biosciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, 90050-170, Brazil.
Biomedical Science Undergraduate Program, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, 90050-170, Brazil.
Mol Neurobiol. 2025 Feb;62(2):1788-1799. doi: 10.1007/s12035-024-04360-9. Epub 2024 Jul 22.
Obesity and aging collectively potentiate inflammatory responses, particularly within the central nervous system. Managing obesity presents a significant challenge, even more so considering the context of aging. Caloric restriction (CR) has been extensively documented in the literature for its multiple health benefits. Motivated by these findings, we hypothesized that CR could serve as a valuable intervention to address the brain alterations and cognitive decline associated with obesity in aged rats. Our investigation revealed that cafeteria diet increased hippocampal and hypothalamic transcripts related to neuroinflammation, along with cognitive deficits determined in the object recognition test in 18-month-old male rats. Western blot data indicate that the obesogenic diet may disrupt the blood-brain barrier and lead to an increase in Toll-like receptor 4 in the hippocampus, events that could contribute to the cognitive deficits observed. Implementing CR after the onset of obesity mitigated neuroinflammatory changes and cognitive impairments. We found that CR increases GABA levels in the hippocampus of aged animals, as demonstrated by liquid chromatography coupled with mass spectrometry analysis. These findings underscore the potential of CR as a therapeutic opportunity to ameliorate the neuroinflammatory and cognitive alterations of obesity, especially in the context of aging.
肥胖和衰老共同加剧炎症反应，尤其是在中枢神经系统内。控制肥胖是一项重大挑战，考虑到衰老的背景，情况更是如此。热量限制（CR）因其多种健康益处已在文献中得到广泛记载。受这些发现的启发，我们假设CR可作为一种有价值的干预措施，以解决老年大鼠中与肥胖相关的大脑改变和认知衰退问题。我们的研究表明，在18个月大的雄性大鼠中，自助餐式饮食增加了与神经炎症相关的海马体和下丘脑转录本，同时在物体识别测试中也出现了认知缺陷。蛋白质印迹数据表明，致肥胖饮食可能会破坏血脑屏障，并导致海马体中Toll样受体4增加，这些事件可能导致观察到的认知缺陷。肥胖发生后实施CR可减轻神经炎症变化和认知障碍。我们发现，通过液相色谱-质谱联用分析表明，CR可增加老年动物海马体中的γ-氨基丁酸（GABA）水平。这些发现强调了CR作为一种治疗手段的潜力，可改善肥胖引起的神经炎症和认知改变，尤其是在衰老的背景下。
