Research Article: Neurocalcin-delta: a potential memory-related factor in hippocampus of obese rats induced by high-fat diet

Date Published: December , 2017

Publisher: Makerere Medical School

Author(s): Wei-Wei Ma, Bing-Jie Ding, Lin-Hong Yuan, Lei Zhao, Huan-Ling Yu, Yuan-di Xi, Rong Xiao.


Aberrant protein expression within the hippocampus has recently been implicated in the pathogenesis of obesity-induced memory impairment.

The objective of the current study was to search for specific memory-related factors in the hippocampus in obese rats.

Sprague-Dawley (SD) rats were fed either a high-fat (HF) diet or normal-fat (NF) diet for 10 weeks to obtain the control (CON), diet-induced obese rats (DIO) and diet-resistant (DR) rats. D-galactose was injected subcutaneously for 10 weeks to establish model (MOD) rats with learning and memory impairment. After the hippocampus of the rats sampling, the proteome analysis was conducted using two-dimensional get electrophoresis (2-DE) combined with peptide mass fingerprinting (PMF).

We found 15 differential proteins that expressed in the hippocampus in rats induced by HF diet from the 2-DE map. In addition, Neurocalcin-delta (NCALD) was nearly down-regulated in the DR rats compared with CON rats and MOD rats, which was further confirmed by Western blot, real-time PCR and ELISA results.

Our data demonstrates that the differential memory-related proteins were a reflection of the HF diet, but not potential factors in obesity proneness or obesity resistance. Furthermore, NCALD is proved to be a potential hippocampus-memory related factor related to obesity.

Partial Text

Obesity, a chronic metabolic disease, represents one of the most serious public health and societal problems for the coming decades1, which affects greater than 35% of the population of U.S and an estimated 670 million people worldwide2. Obesity has been associated with a multitude of diseases, including cardiovascular disease, diabetes, hypertension, and certain cancers3–5. In addition, recent evidence has also highlighted that obesity is associated with cognitive impairments and with an increased risk of developing dementia and alzheimer’s disease (AD) later in life6–8. Epidemiological studies suggest that presence of obesity increases the incidence of numerous neuro-degenerative conditions including AD8,9. The rate of cognitive dysfunction happened in obese people was significantly higher than that of normal-weighted people10–13. Such results are essential in understanding the mechanisms for the role of obesity in modulating neuro-degenerative processes14. Rodent studies indicate that Sprague-Dawley (SD) rats showed impaired learning and cognitive functions after being fed with the high-fat (HF) diets15, complicated with damaged neurons in the hippocampus. This result is consistent with our previous studies16,17.

Data were presented as mean ± standard error (S.E) and analyzed with the software SPSS 13.0. The means among groups were compared with one-way ANOVA followed by LSD post-hoc test. A two-tailed p<0.05 was considered to be significantly different. In our previous study, rats showed high distinct susceptibility to develop obesity when the rats were fed with a HF diet. In the present study, SD rats were fed with either a HF diet or a NF diet for 10 weeks to generate the CON, DIO and DR rats. The availability of DIO and DR rats are crucial in exploring the mechanisms for development of obesity. D-galactose was injected sub-cutaneously for 10 weeks to establish model (MOD) rats with learning and memory impairments. The final body weight, the perirenal fat, the testicular fat, omental fat and body fat mass of DIO rats were higher than that of DR rats17. MOD rats showed impaired learning and memory ability compared with the CON rats16. Alerted protein expression within the hippocampus has recently been implicated in the pathogenesis of obesity-induced memory impairments. Thus, in the present study, we aimed to investigate the differential protein expression in the DIO and DR rats by using 2-D gel electrophoresis and PMF. In summary, proteomic analysis of rat hippocampus has provided a useful method to detect differentially expressed proteins in obesity-induced memory impairments. We found the potential memory-related factors as a reflection of HF diet and obesity. Further studies are required to determine the biochemical and physiological functions of these proteins and their relationship with the development of obesity.   Source:


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