Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA; Department of Pediatrics, Keck School of Medicine of USC, Los Angeles, California, USA; Division of Research on Children, Youth & Families, Children's Hospital Los Angeles, Los Angeles, California, USA; Developmental Neuroscience and Neurogenetics Program, The Saban Research Institute, Los Angeles, California, USA.
J Nutr Biochem. 2023 Apr;114:109220. doi: 10.1016/j.jnutbio.2022.109220. Epub 2022 Nov 23.
The incidence of adolescent mental health disorders is on the rise. Epidemiological studies suggest that poor nutrition is a significant contributor to this public health crisis, specifically through exposure to high level of dietary sugar, including fructose, during critical periods of development. Previous studies have shown that elevated fructose exposure during adolescence disrupts mental health. Despite these data, it is currently unknown how fructose exposure, specifically during infancy, may impact adolescent mental health. We developed a rat experimental protocol to investigate the effects of fructose exposure during infancy on behavioral, cognitive and metabolic endpoints in adolescence. We found that exposing rats to high fructose from birth to weaning resulted in higher circulating glucose, insulin and leptin levels in adolescence. High fructose during infancy also increased bodyweight, disrupted metabolic homeostasis in the basolateral amygdala (BLA) as indicated by decreased activity of the cellular energy sensor AMPK, and impaired attention and impulsivity in a male-specific manner. This impaired attention observed in adolescent male rats following neonatal fructose exposure was partially rescued by viral-mediated, in vivo expression of a constitutively active form of AMPK in principal neurons of the BLA. Our results suggest that exposure to high level of fructose during infancy may impact adolescent mental health in a male-specific manner and that manipulation of AMPK activity may mitigate this impact.
青少年心理健康障碍的发病率正在上升。流行病学研究表明，不良营养是这一公共卫生危机的一个重要促成因素，特别是在发育的关键时期接触高水平的膳食糖，包括果糖。先前的研究表明，青春期果糖暴露水平升高会破坏心理健康。尽管有这些数据，但目前尚不清楚果糖暴露，特别是在婴儿期，如何影响青少年的心理健康。我们开发了一种大鼠实验方案，以研究婴儿期果糖暴露对青春期行为、认知和代谢终点的影响。我们发现，从出生到断奶期间暴露于高果糖会导致青春期循环葡萄糖、胰岛素和瘦素水平升高。婴儿期的高果糖还会增加体重，如细胞能量传感器 AMPK 的活性降低所表明的那样，破坏基底外侧杏仁核 (BLA) 的代谢稳态，并以雄性特异性的方式损害注意力和冲动性。在青春期雄性大鼠中，新生儿果糖暴露后观察到的注意力受损部分可以通过在 BLA 的主神经元中表达病毒介导的 AMPK 的组成激活形式来挽救。我们的研究结果表明，婴儿期暴露于高水平的果糖可能以雄性特异性的方式影响青少年的心理健康，而操纵 AMPK 活性可能会减轻这种影响。
