{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:43:32Z","timestamp":1790675012889,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Waseda University Advanced Research Center for Human Sciences","award":["2019"],"award-info":[{"award-number":["2019"]}]},{"name":"the Waseda University Grant for Special Research Projects","award":["2019C-341"],"award-info":[{"award-number":["2019C-341"]}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["17K08621"],"award-info":[{"award-number":["17K08621"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["20H03408"],"award-info":[{"award-number":["20H03408"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["19K08060"],"award-info":[{"award-number":["19K08060"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"the Takeda Science Foundation","doi-asserted-by":"publisher","award":["2019"],"award-info":[{"award-number":["2019"]}],"id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016339","name":"Japan Society for Bioscience, Biotechnology, and Agrochemistry","doi-asserted-by":"publisher","award":["2019"],"award-info":[{"award-number":["2019"]}],"id":[{"id":"10.13039\/100016339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Obesity is characterized by massive adipose tissue accumulation and is associated with psychiatric disorders and cognitive impairment in human and animal models. However, it is unclear whether high-fat diet (HFD)-induced obesity presents a risk of psychiatric disorders and cognitive impairment. To examine this question, we conducted systematic behavioral analyses in C57BL\/6J mice (male, 8-week-old) fed an HFD for 7 weeks. C57BL\/6J mice fed an HFD showed significantly increased body weight, hyperlocomotion in the open-field test (OFT) and Y-maze test (YMZT), and impaired sucrose preference in the sucrose consumption test, compared to mice fed a normal diet. Neither body weight nor body weight gain was associated with any of the behavioral traits we examined. Working memory, as assessed by the YMZT, and anxiety-like behavior, as assessed by the elevated plus maze test (EPMT), were significantly correlated with mice fed an HFD, although these behavioral traits did not affect the entire group. These results suggest that HFD-induced obesity does not induce neuropsychiatric symptoms in C57BL\/6J mice. Rather, HFD improved working memory in C57BL\/6J mice with less anxiety, indicating that an HFD might be beneficial under limited conditions. Correlation analysis of individual traits is a useful tool to determine those conditions.<\/jats:p>","DOI":"10.3390\/nu12072036","type":"journal-article","created":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T10:45:19Z","timestamp":1594291519000},"page":"2036","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":146,"title":["High-Fat Diet Enhances Working Memory in the Y-Maze Test in Male C57BL\/6J Mice with Less Anxiety in the Elevated Plus Maze Test"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2540-332X","authenticated-orcid":false,"given":"Kaichi","family":"Yoshizaki","sequence":"first","affiliation":[{"name":"Department of Disease Model, Institute for Developmental Research, Aichi Developmental Disability Center, Aichi 480-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6397-373X","authenticated-orcid":false,"given":"Masato","family":"Asai","sequence":"additional","affiliation":[{"name":"Department of Disease Model, Institute for Developmental Research, Aichi Developmental Disability Center, Aichi 480-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4722-6336","authenticated-orcid":false,"given":"Taichi","family":"Hara","sequence":"additional","affiliation":[{"name":"Laboratory of Food and Life Science, Faculty of Human Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/obr.12089","article-title":"Genetic factors in exercise adoption, adherence and obesity","volume":"15","author":"Herring","year":"2014","journal-title":"Obes. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1467-789X.2007.00315.x","article-title":"Genetic factors in human obesity","volume":"8","author":"Farooqi","year":"2007","journal-title":"Obes. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1017\/S0007114513001116","article-title":"Genetic predisposition to obesity and lifestyle factors\u2014The combined analyses of twenty-six known BMI- and fourteen known waist:hip ratio (WHR)-associated variants in the Finnish Diabetes Prevention Study","volume":"110","author":"Paananen","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.molmet.2012.07.002","article-title":"Obesity and the gut microbiome: Striving for causality","volume":"1","author":"Harley","year":"2012","journal-title":"Mol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.molmet.2012.07.005","article-title":"An inconvenient truth about obesity","volume":"1","author":"Schwartz","year":"2012","journal-title":"Mol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/j.1463-1326.2010.01353.x","article-title":"Pharmaceutical interventions for obesity: A public health perspective","volume":"13","author":"Caveney","year":"2011","journal-title":"Diabetes Obes. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1001\/archgenpsychiatry.2010.2","article-title":"Overweight, obesity, and depression: A systematic review and meta-analysis of longitudinal studies","volume":"67","author":"Luppino","year":"2010","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.biopsych.2015.10.023","article-title":"Leptin dysregulation is specifically associated with major depression with atypical features: Evidence for a mechanism connecting obesity and depression","volume":"81","author":"Milaneschi","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/oby.21441","article-title":"High-fat diet feeding alters olfactory-, social-, and reward-related behaviors of mice independent of obesity","volume":"24","author":"Takase","year":"2016","journal-title":"Obesity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e1428","DOI":"10.4088\/JCP.14m09009","article-title":"Inflammation, obesity, and metabolic syndrome in depression: Analysis of the 2009\u20132010 National Health and Nutrition Examination Survey (NHANES)","volume":"75","author":"Rethorst","year":"2014","journal-title":"J. Clin. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1001\/jamapsychiatry.2014.411","article-title":"Depression with atypical features and increase in obesity, body mass index, waist circumference, and fat mass: A prospective, population-based study","volume":"71","author":"Lasserre","year":"2014","journal-title":"JAMA Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s11011-013-9412-4","article-title":"Neurodegenerative disease and obesity: What is the role of weight loss and bariatric interventions?","volume":"28","author":"Ashrafian","year":"2013","journal-title":"Metab. Brain Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0896-6273(03)00840-7","article-title":"Cholesterol and the biology of Alzheimer\u2019s disease","volume":"41","author":"Wolozin","year":"2004","journal-title":"Neuron"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e426","DOI":"10.1111\/j.1467-789X.2010.00825.x","article-title":"Body mass index in midlife and late-life as a risk factor for dementia: A meta-analysis of prospective studies","volume":"12","author":"Anstey","year":"2011","journal-title":"Obes. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"637","DOI":"10.3390\/nu5030637","article-title":"Naringin improves diet-induced cardiovascular dysfunction and obesity in high carbohydrate, high fat diet-fed rats","volume":"5","author":"Alam","year":"2013","journal-title":"Nutrients"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"301","DOI":"10.2147\/IJN.S52414","article-title":"Anti-obesity efficacy of nanoemulsion oleoresin capsicum in obese rats fed a high-fat diet","volume":"9","author":"Kim","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"35239","DOI":"10.1038\/srep35239","article-title":"The effects of high-fat-diet combined with chronic unpredictable mild stress on depression-like behavior and leptin\/LepRb in male rats","volume":"6","author":"Yang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ynstr.2018.05.005","article-title":"Effects of high fat or high sucrose diet on behavioral-response to social defeat stress in mice","volume":"9","author":"Eudave","year":"2018","journal-title":"Neurobiol. Stress"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.neuroscience.2018.01.001","article-title":"High-fat diet mediates anxiolytic-like behaviors in a time-dependent manner through the regulation of SIRT1 in the rain","volume":"372","author":"Xu","year":"2018","journal-title":"Neuroscience"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"277","DOI":"10.5607\/en.2018.27.4.277","article-title":"Assessment of cognitive impairment in a mouse model of high-fat diet-induced metabolic stress with touchscreen-based automated battery system","volume":"27","author":"Lee","year":"2018","journal-title":"Exp. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1093\/gerona\/glu080","article-title":"Aging exacerbates obesity-induced cerebromicrovascular rarefaction, neurovascular uncoupling, and cognitive decline in mice","volume":"69","author":"Tucsek","year":"2014","journal-title":"J. Gerontol A Biol. Sci. Med. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1111\/j.1471-4159.2010.06865.x","article-title":"High fat diet increases hippocampal oxidative stress and cognitive impairment in aged mice: Implications for decreased Nrf2 signaling","volume":"114","author":"Morrison","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1080\/09168451.2017.1401912","article-title":"Food-derived regulatory factors against obesity and metabolic syndrome","volume":"82","author":"Kawada","year":"2018","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1093\/jn\/116.7.1272","article-title":"Effects of capsaicin on lipid metabolism in rats fed a high fat diet","volume":"116","author":"Kawada","year":"1986","journal-title":"J. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3181\/00379727-183-42414","article-title":"Capsaicin-induced beta-adrenergic action on energy metabolism in rats: Influence of capsaicin on oxygen consumption, the respiratory quotient, and substrate utilization","volume":"183","author":"Kawada","year":"1986","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3181\/00379727-188-2-RC1","article-title":"Some pungent principles of spices cause the adrenal medulla to secrete catecholamine in anesthetized rats","volume":"188","author":"Kawada","year":"1988","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kim, Y.I., Hirai, S., Goto, T., Ohyane, C., Takahashi, H., Tsugane, T., Konishi, C., Fujii, T., Inai, S., and Iijima, Y. (2012). Potent PPAR\u03b1 activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031317"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1002\/mnfr.201100401","article-title":"Auraptene regulates gene expression involved in lipid metabolism through PPAR\u03b1 activation in diabetic obese mice","volume":"55","author":"Takahashi","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E1022","DOI":"10.1152\/ajpendo.00061.2011","article-title":"Farnesol, an isoprenoid, improves metabolic abnormalities in mice via both PPAR\u03b1-dependent and -independent pathways","volume":"301","author":"Goto","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yoshizaki, K., Furuse, T., Kimura, R., Tucci, V., Kaneda, H., Wakana, S., and Osumi, N. (2016). Paternal aging affects behavior in Pax6 mutant mice: A gene\/environment nteraction in understanding neurodevelopmental disorders. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166665"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6390","DOI":"10.1093\/hmg\/ddv350","article-title":"De novo inbred heterozygous Zeb2\/Sip1 mutant mice uniquely generated by germ-line conditional knockout exhibit craniofacial, callosal and behavioral defects associated with Mowat-Wilson syndrome","volume":"24","author":"Takagi","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1038\/npp.2013.38","article-title":"Deficiency of schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia","volume":"38","author":"Takao","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.neubiorev.2005.03.007","article-title":"Stress, depression, and anhedonia: Caveats concerning animal models","volume":"29","author":"Anisman","year":"2005","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.neuron.2010.12.023","article-title":"Epigenetic status of Gdnf in the ventral striatum determines susceptibility and adaptation to daily stressful events","volume":"69","author":"Uchida","year":"2011","journal-title":"Neuron"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Yoshizaki, K., Koike, K., Kimura, R., and Osumi, N. (2017). Early postnatal vocalizations predict sociability and spatial memory in C57BL\/6J mice: Individual differences in behavioral traits emerge early in development. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186798"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.bbr.2012.12.011","article-title":"Prepulse inhibition predicts working memory performance whilst startle habituation predicts spatial reference memory retention in C57BL\/6 mice","volume":"242","author":"Singer","year":"2013","journal-title":"Behav. Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s002130050327","article-title":"Behavioral phenotypes of inbred mouse strains: Implications and recommendations for molecular studies","volume":"132","author":"Crawley","year":"1997","journal-title":"Psychopharmacology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1007\/s002130050038","article-title":"Differences in anxiety-related behaviours and in sensitivity to diazepam in inbred and outbred strains of mice","volume":"148","author":"Griebel","year":"2000","journal-title":"Psychopharmacology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0166-4328(99)00072-8","article-title":"Use of SHIRPA and discriminant analysis to characterise marked differences in the behavioural phenotype of six inbred mouse strains","volume":"105","author":"Rogers","year":"1999","journal-title":"Behav. Brain Res."},{"key":"ref_40","first-page":"505","article-title":"Characteristics of open field behavior of Wistar and Sprague-Dawley rats","volume":"35","author":"Asano","year":"1986","journal-title":"Jikken Dobutsu."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00504983","article-title":"Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of \u2019fear\u2019-motivated behaviour","volume":"327","author":"Handley","year":"1984","journal-title":"Naunyn Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/BF00177912","article-title":"The use of a plus-maze to measure anxiety in the mouse","volume":"92","author":"Lister","year":"1987","journal-title":"Psychopharmacology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0165-0270(85)90031-7","article-title":"Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat","volume":"14","author":"Pellow","year":"1985","journal-title":"J. Neurosci. Methods"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0166-4328(93)90045-R","article-title":"Anxiolytic effects of serotonergic interventions in the shock-probe burying test and the elevated plus-maze test","volume":"54","author":"Treit","year":"1993","journal-title":"Behav. Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1242\/dmm.003467","article-title":"Mouse model of the metabolic syndrome","volume":"3","author":"Kennedy","year":"2010","journal-title":"Dis. Model. Mech."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/7\/2036\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:49:17Z","timestamp":1760176157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/7\/2036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,9]]},"references-count":45,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["nu12072036"],"URL":"https:\/\/doi.org\/10.3390\/nu12072036","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,9]]}}}