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Behavior, Psychology and Sociology

Saturated fatty acid is a principal cause of anxiety-like behavior in diet-induced obese rats in relation to serum lysophosphatidyl choline level



Obesity is considered to be a risk factor for neurodegenerative- and psychiatric- diseases including Alzheimer’s disease, schizophrenia, and depression. A high-lard diet is widely used to induce obesity in model animal experiments, which also leads to anxiety-like and depression-like behaviors. However, the contribution of dietary fat source to these abnormal behaviors in obesity is largely unknown.


Sprague-Dawley rats were treated with different types of high-fat (lard and olive oil) diet with high sucrose for more than 8 weeks. Anxiety-like behavior (open-field and social interaction tests) and cognitive function (Y-maze test) after the treatment were analyzed. The expression of mRNA related to neurotransmitter and nutrient transporters in the prefrontal cortex were determined using real-time PCR. Serum lipid species were determined using liquid chromatography with tandem mass spectrometry.


Both high-fat/high-sucrose diets increased body weight (BW), adipose tissue, and serum leptin level. However, the high-lard/high-sucrose (HL/HS), but not high-olive oil/HS, diet induced anxiety-like behavior in open field and social interaction tests. BW and endocrine hormones such as leptin and insulin were not correlated to anxiety-like behavior. HL/HS diet induced an increase in glutamate transporter and a decrease of glutamate receptor mRNA expressions in the prefrontal cortex. Further, serum lysophosphatidyl choline conjugated with several fatty acids was decreased by HL/HS diet. LPC conjugated with eicosapentaenoic acid (EPA) was strongly correlated with anxiety-like behavior.


These results suggest that lipid composition, rather than obesity per se, is a major cause of anxiety-like behavior in high-fat diet-induced obesity. Decreased levels of peripheral LPC conjugated with EPA and altered glutamate system in the prefrontal cortex might be involve in the pathophysiology of the behavioral change.

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This research was supported by JSPS KAKENHI Grant numbers 16K16589 (SN), 26860144 (MG), and the Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and development, AMED Grant number 17dm0107100h0002 (HK).

Author contributions

SN designed research; SN, and KF, conducted research and analyzed data; SN wrote the paper; MG, KM-M, and HK reviewed and edited the paper. SN had primary responsibility for final content. All authors read and approved the final paper.

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Correspondence to Shingo Nakajima.

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Nakajima, S., Fukasawa, K., Gotoh, M. et al. Saturated fatty acid is a principal cause of anxiety-like behavior in diet-induced obese rats in relation to serum lysophosphatidyl choline level. Int J Obes 44, 727–738 (2020).

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