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

• Published in: International Journal of Obesity Vol. 44; no. 3; pp. 727 - 738
• Main Authors: Nakajima, Shingo, Fukasawa, Keiko, Gotoh, Mari, Murakami-Murofushi, Kimiko, Kunugi, Hiroshi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2020; Nature Publishing Group
• Subjects: 101/58; 631/378; 631/443/319/1642/393; 631/45/608; 82/16; Adipose tissue; Alzheimer's disease; Animals; Anxiety; Anxiety - chemically induced; Behavior; Behavior, Animal - drug effects; Body weight; Choline; Cognitive ability; Complications and side effects; Diet; Diet, High-Fat; Dietary fat; Disease Models, Animal; Eicosapentaenoic acid; Epidemiology; Fatty acids; Fatty Acids - pharmacology; Gene expression; Glutamate receptors; Glutamic acid transporter; Health aspects; Health Promotion and Disease Prevention; High fat diet; Hormones; Insulin; Internal Medicine; Lecithin; Leptin; Lipid composition; Lipids; Liquid chromatography; Lysophosphatidylcholines - blood; Male; Mass spectrometry; Mass spectroscopy; Medicine; Medicine & Public Health; Mental depression; Mental disorders; Metabolic Diseases; mRNA; Neurodegenerative diseases; Neurotransmitters; Obesity; Obesity - physiopathology; Oils & fats; Olive oil; Open-field behavior; Prefrontal cortex; Psychological aspects; Public Health; Rats; Rats, Sprague-Dawley; Risk analysis; Risk factors; Schizophrenia; Social behavior; Social factors; Social interaction; Sucrose; Sucrose - pharmacology; Sugar; Japan
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/s41366-019-0468-z

Background 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. Methods 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. Results 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. Conclusions 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.