Sex differences in high-fat diet-induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice.
Obesity is a potential risk factor for cognitive deficits in the elder humans. Using a high-fat diet (HFD)-induced obese mouse model, we investigated the impacts of HFD on obesity, metabolic and stress hormones, learning performance, and hippocampal synaptic plasticity. Both male and female C57BL/6J mice fed with HFD (3 weeks to 9-12 months) gained significantly more weights than the sex-specific control groups. Compared with the obese female mice, the obese males had similar energy intake but developed more weight gains. The obese male mice developed hyperglycemia, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia, but not hypertriglyceridemia. The obese females had less hyperinsulinemia and hypercholesterolemia than the obese males, and no hyperglycemia and hypertriglyceridemia. In the contextual fear conditioning and step-down passive avoidance tasks, the obese male, but not female, mice showed poorer learning performance than their normal counterparts. These learning deficits were not due to sensorimotor impairment as verified by the open-field and hot-plate tests. Although, basal synaptic transmission characteristics (input-output transfer and paired-pulse facilitation (PPF) ratio) were not significantly different between normal and HFD groups, the magnitudes of synaptic plasticity (long-term potentiation (LTP) and long-term depression (LTD)) were lower at the Schaffer collateral-CA1 synapses of the hippocampal slices isolated from the obese male, but not female, mice, as compared with their sex-specific controls. Our results suggest that male mice are more vulnerable than the females to the impacts of HFD on weight gains, metabolic alterations and deficits of learning, and hippocampal synaptic plasticity.
Hwang
Ling-Ling
LL
Department of Physiology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Wang
Chien-Hua
CH
Li
Tzu-Ling
TL
Chang
Shih-Dar
SD
Lin
Li-Chun
LC
Chen
Ching-Ping
CP
Chen
Chiung-Tong
CT
Liang
Keng-Chen
KC
Ho
Ing-Kang
IK
Yang
Wei-Shiung
WS
Chiou
Lih-Chu
LC
D000818:Animals; D001362:Avoidance Learning; D003072:Cognition Disorders / Q000209:etiology*; D003214:Conditioning, Classical; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D002149:Energy Intake; D005239:Fear; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D006943:Hyperglycemia / Q000209:etiology; D006946:Hyperinsulinism / Q000209:etiology; D006949:Hyperlipidemias / Q000209:etiology; D007858:Learning; D036881:Long-Term Synaptic Depression; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D011897:Random Allocation; D012737:Sex Factors; D009435:Synaptic Transmission; D015430:Weight Gain
D004041:Dietary Fats