IMR Press / JIN / Volume 22 / Issue 1 / DOI: 10.31083/j.jin2201016
Open Access Original Research
Effects of Prolonged High-Fat Diet Consumption Starting at Different Ages on Behavioral Parameters and Hippocampal Neuroplasticity in Male Mice
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1 Department of Physiology, Medical College, Southeast University, 210009 Nanjing, Jiangsu, China
2 School of Life Science and Technology, Southeast University, 210009 Nanjing, Jiangsu, China
3 School of Public Health, Southeast University, 210009 Nanjing, Jiangsu, China
*Correspondence: (Lijie Liu)
Academic Editor: Irene Messina
J. Integr. Neurosci. 2023, 22(1), 16;
Submitted: 12 August 2022 | Revised: 4 September 2022 | Accepted: 9 September 2022 | Published: 13 January 2023
(This article belongs to the Special Issue Neural Bases of Emotion Regulation and Emotion Processing)
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: 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. Methods: 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. Results: 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. Conclusions: These results not only provide in vivo 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.

high-fat diet
insulin resistance
hippocampal neuroplasticity
82171541/National Natural Science Foundation of China
81970893/National Natural Science Foundation of China
81670935/National Natural Science Foundation of China
JSKLCCM-2022-02-002/Jiangsu Provincial Key Lab-oratory of Critical Care Medicine
Fig. 1.
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