Reduced neurotrophic factor level is the early event before the functional neuronal deficiency in high-fat diet induced obese mice.
Neurodegeneration is considered one of the possible complications of high fat diet (HFD) induced obesity. Much evidence has shown the close relationship between HFD and dementia at comparatively later stage of neuronal injury. It is so far not clear that the initial events of neuronal injury resulting from HFD and obesity. In the present research, obese mouse model achieved by 3-month HFD was applied for the investigation of the possible neuronal deficiency before the obvious cognitive decline. We found that 3-month HFD has already increased the average level of body weight of mice. But almost no obvious cognitive defect was observed. At such time point, we detected the cleavage of amyloid precursor protein (APP), including the expression and maturation level of α- and β-secretase and proteolytic fragment soluble APP. Results showed similar readout between HFD and normal diet (ND) mice. Besides, neuronal inflammation and brain-blood barrier permeability were also detected. No obvious changes could be observed between HFD and ND mice. Surprisingly, the first detectable neuronal changes was showed to be the downregulation of some neurotrpic factors, like neuronal growth factor β and brain derived neurotrophic factor, together with the activity of specific receptors, like Trk receptor phosphorylation. All the data piled up indicated that the early neuronal change in HFD induced obese mice was the downregulation of some neurotrophic factors. The results may provide the potential clue to therapeutic and preventive strategy for HFD induced cognitive decline.
School of Medicine, Hangzhou Normal University, Xuelin Street 16#,, Hangzhou, 310036, China. huanval@hznu.edu.cn.
Huanhuan
H
Wang
College of Life Science, Hangzhou Normal University, Hangzhou, China.
Bing
B
Wang
School of Medicine, Hangzhou Normal University, Xuelin Street 16#,, Hangzhou, 310036, China.
Hongping
H
Yin
College of Public Health, Dalian Medical University, Dalian, China.
Guoqing
G
Zhang
Center of Laboratory Animal, Hangzhou Normal University, Hangzhou, China.
Liping
L
Yu
School of Medicine, Hangzhou Normal University, Xuelin Street 16#,, Hangzhou, 310036, China.
Xiangmin
X
Kong
Department of Clinical Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
Haiying
H
Yuan
College of Science, Hainan Medical School, Hainan, China.
Xingyue
X
Fang
College of Science, Hainan Medical School, Hainan, China.
Qibing
Q
Liu
College of Basic Medicine, Zhejiang Chinese Medical University, Zhejiang, China.
Cuiqing
C
Liu
Department of Immunology, Nanjing University of Traditional Chinese Medicine, Xianlin Street 138#,, Nanjing, 210023, China. shi_liyun@msn.com.
Liyun
L
Shi
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D020813:Receptor, trkB / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; C000621230:Ntrk2 protein, rat; D020813:Receptor, trkB
Amyloid precursor protein; High-fat diet; Neuroinflammation; Neurotrophic factor