Department of Physiology, Medical College, Southeast University, 210009 Nanjing, Jiangsu, China.
School of Life Science and Technology, Southeast University, 210009 Nanjing, Jiangsu, China.
J Integr Neurosci. 2023 Jan 13;22(1):16. doi: 10.31083/j.jin2201016.
The overconsumption of a high-fat diet (HFD) has been repeatedly blamed as being a possible contributor to the global prevalence of emotional problems in modern society. Our group recently demonstrated the deleterious effect of a chronic HFD throughout adulthood on both emotional behavior and neuroplasticity markers in mice. As a heightened preference for palatable HFDs from the time of the juvenile period (when the brain is particularly vulnerable to environmental insults) is universal among populations around the world, a comparison of the consequences of chronic HFDs starting from juveniles or adults will assist in obtaining better knowledge of the impact that chronic HFDs have on mental health, thus potentially leading to the discovery of more effective strategies for reducing the incidence of psychiatric disorders.
In the present study, male C57BL/6J mice with an initial age of 4 weeks (IA-4 W) or 8 weeks (IA-8 W) were separately assigned to two subgroups and fed either a control diet (CD, 10 kJ% from fat) or HFD (60 kJ% from fat) for 9 months followed by an analysis focused on metabolic, emotional behavioral, and neuroplastic profiles.
The results illustrated that, in addition to abnormal glucolipid metabolism and insulin sensitivity, mice on a chronic HFD exhibited increased levels of anxiety and depression-like behaviors and aberrant hippocampal neuroplasticity. When compared with IA-8 W mice, several changes indicating systemic metabolic disturbance and neurobehavioral disorder after chronic HFD consumption were aggravated in IA-4 W mice, accompanied by exaggerated impairments in hippocampal insulin sensitivity and neurogenesis.
These results not only provide evidence that the juvenile stage is a critical period of vulnerability to detrimental effects of HFD consumption on metabolic and neuronal function but also suggest dampened hippocampal insulin signaling as a potential link between prolonged HFD consumption and negative neurobehavioral outcomes. Considering the substantial burden posed by psychiatric disorders and the high prevalence of HFD among youth, these observations are meaningful for raising awareness of the harmful effects of excessive dietary fat intake and developing strategy for preventing mental disorders.
高脂肪饮食（HFD）的过度摄入被反复指责为现代社会全球情绪问题普遍存在的一个可能原因。我们小组最近证明，成年期慢性 HFD 对小鼠的情绪行为和神经可塑性标志物都有有害影响。由于全世界的人群在青少年时期（大脑特别容易受到环境刺激）都普遍存在对美味 HFD 的偏好增加，因此比较从青少年或成年开始的慢性 HFD 的后果将有助于更好地了解慢性 HFD 对心理健康的影响，从而有可能发现更有效的策略来降低精神疾病的发病率。
在本研究中，初始年龄为 4 周（IA-4 W）或 8 周（IA-8 W）的雄性 C57BL/6J 小鼠分别被分配到两个亚组，分别喂食对照饮食（CD，脂肪供能 10 kJ%）或 HFD（脂肪供能 60 kJ%）9 个月，然后分析重点放在代谢、情绪行为和神经可塑性方面。
结果表明，除了异常的糖脂代谢和胰岛素敏感性外，慢性 HFD 组的小鼠表现出焦虑和抑郁样行为增加以及海马神经可塑性异常。与 IA-8 W 小鼠相比，IA-4 W 小鼠在慢性 HFD 消耗后表现出更严重的全身代谢紊乱和神经行为障碍，同时伴随着海马胰岛素敏感性和神经发生的明显损伤。
这些结果不仅提供了证据，证明青少年期是易受 HFD 摄入对代谢和神经元功能产生不利影响的关键时期，而且还表明延长 HFD 摄入与负面神经行为结果之间存在海马胰岛素信号减弱的潜在联系。考虑到精神疾病的巨大负担和青少年中 HFD 的高流行率，这些观察结果对于提高对过度饮食脂肪摄入的有害影响的认识和制定预防精神障碍的策略具有重要意义。
