{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:22:28Z","timestamp":1790605348737,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Evidence supports the role of exercise training and probiotics on reducing obesity. Considering the relationship between obesity and high-fat diet with anxiety indices, the aim of this study was to assess the effect of probiotic supplementation and high-intensity interval training (HIIT) on anxiety-like behaviors, corticosterone and obesity indices in high-fat diet (HFD)-induced obesity mice. Thirty male adult C57BL\/6 mice were randomly divided into five groups: (1) Control with normal diet (CON), (2) High-fat diet (HFD), (3) HFD + exercise training (HT), (4) HFD + probiotics supplement (HP) and (5) HFD + exercise training +probiotics (HTP). Exercise training consisted of 8 weeks of high-intensity interval training (HIIT) programs. Probiotics supplement included 0.2 mL Lactobacillus rhamnosus GG. Anxiety-like behaviors were measured by open field (OF) and Elevated plus maze (EPM). OF and EPM tests, visceral fat mass (VFM) measurement, and blood sampling for corticosterone were performed after the intervention. Bodyweight was measured at different stages during the intervention. HFD regime in C57BL\/6 mice increased bodyweight, VFM, and serum corticosterone levels and anxiety-like behaviors (p &lt; 0.05). HIIT, probiotic and their combination, decreased bodyweight, VFM, and serum corticosterone levels and improved anxiety-like behavior in the HFD mice (p &lt; 0.05). The effect of a combination of HIIT and probiotic on most of the anxiety indices was more than each one separately (p &lt; 0.5). HIIT and probiotic supplements separately or above all in combination, may have beneficial effects in reducing obesity and anxiety indices.<\/jats:p>","DOI":"10.3390\/nu13061762","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:01:20Z","timestamp":1621814480000},"page":"1762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Probiotic Supplementation and High-Intensity Interval Training Modify Anxiety-Like Behaviors and Corticosterone in High-Fat Diet-Induced Obesity Mice"],"prefix":"10.3390","volume":"13","author":[{"given":"Parisa","family":"Foroozan","sequence":"first","affiliation":[{"name":"Department of Sport Sciences, School of Education and Psychology, Shiraz University, Shiraz 7194684334, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9563-9461","authenticated-orcid":false,"given":"Maryam","family":"Koushkie Jahromi","sequence":"additional","affiliation":[{"name":"Department of Sport Sciences, School of Education and Psychology, Shiraz University, Shiraz 7194684334, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javad","family":"Nemati","sequence":"additional","affiliation":[{"name":"Department of Sport Sciences, School of Education and Psychology, Shiraz University, Shiraz 7194684334, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hosein","family":"Sepehri","sequence":"additional","affiliation":[{"name":"Department of Sport Sciences, School of Education and Psychology, Shiraz University, Shiraz 7194684334, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Amin","family":"Safari","sequence":"additional","affiliation":[{"name":"Department of Sport Sciences, School of Education and Psychology, Shiraz University, Shiraz 7194684334, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2175-2765","authenticated-orcid":false,"given":"Serge","family":"Brand","sequence":"additional","affiliation":[{"name":"Center for Affective, Stress and Sleep Disorders (ZASS), Psychiatric University Hospital Basel, 4002 Basel, Switzerland"},{"name":"Department of Clinical Research, University of Basel, 4031 Basel, Switzerland"},{"name":"Substance Abuse Prevention Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6714869914, Iran"},{"name":"Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah 6714869914, Iran"},{"name":"Department of Sport, Exercise and Health, Division of Sport Science and Psychosocial Health, University of Basel, 4052 Basel, Switzerland"},{"name":"School of Medicine, Tehran University of Medical Sciences, Tehran 1417613151, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.physbeh.2016.11.016","article-title":"Behavioral changes in male mice fed a high-fat diet are associated with IL-1\u03b2 expression in specific brain regions","volume":"169","author":"Graham","year":"2017","journal-title":"Physiol. Behav."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Godos, J., Currenti, W., Angelino, D., Mena, P., Castellano, S., Caraci, F., Galvano, F., Del Rio, D., Ferri, R., and Grosso, G. (2020). Diet and Mental Health: Review of the Recent Updates on Molecular Mechanisms. Antioxidants, 9.","DOI":"10.3390\/antiox9040346"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/ijo.2009.252","article-title":"The association between obesity and anxiety disorders in the population: A systematic review and meta-analysis","volume":"34","author":"Gariepy","year":"2010","journal-title":"Int. J. Obes."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1038\/ijo.2017.112","article-title":"HFD-induced energy states-dependent bidirectional control of anxiety levels in mice","volume":"41","author":"Sweeney","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R1001","DOI":"10.1152\/ajpregu.00523.2012","article-title":"Early effects of high-fat diet on neurovascular function and focal ischemic brain injury","volume":"304","author":"Li","year":"2013","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.bbr.2015.02.036","article-title":"Chronic high fat feeding increases anxiety-like behaviour and reduces transcript abundance of glucocorticoid signalling genes in the hippocampus of female rats","volume":"286","author":"Sivanathan","year":"2015","journal-title":"Behav. Brain. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Shen, Y., Huang, G., McCormick, B.P., Song, T., and Xu, X. (2017). Effects of high-intensity interval versus mild-intensity endurance training on metabolic phenotype and corticosterone response in rats fed a high-fat or control diet. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181684"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/09637486.2018.1462309","article-title":"Current evidence linking diet to gut microbiota and brain development and function","volume":"70","author":"Ceppa","year":"2019","journal-title":"Int. J. Food. Sci. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"555","DOI":"10.2174\/1389201021666200107113812","article-title":"The Effects of Probiotics and Prebiotics on Mental Disorders: A Review on Depression, Anxiety, Alzheimer, and Autism Spectrum Disorders","volume":"21","author":"Ansari","year":"2020","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Do, M.H., Lee, E., Oh, M.-J., Kim, Y., and Park, H.-Y. (2018). High-glucose or-fructose diet cause changes of the gut microbiota and metabolic disorders in mice without body weight change. Nutrients, 10.","DOI":"10.3390\/nu10060761"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.bbr.2018.09.010","article-title":"Probiotics modify body weight together with anxiety states via pro-inflammatory factors in HFD-treated Syrian golden hamster","volume":"356","author":"Avolio","year":"2019","journal-title":"Behav. Brain. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.nutres.2015.05.008","article-title":"Probiotics for weight loss: A systematic review and meta-analysis","volume":"35","author":"Park","year":"2015","journal-title":"Nutr. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"266","DOI":"10.3389\/fnbeh.2018.00266","article-title":"Oral probiotics ameliorate the behavioral deficits induced by chronic mild stress in mice via the gut microbiota-inflammation axis","volume":"12","author":"Li","year":"2018","journal-title":"Front. Behav. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s40199-020-00329-w","article-title":"Effect of probiotic administration on gut microbiota and depressive behaviors in mice","volume":"28","author":"Liu","year":"2020","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.gtc.2005.05.011","article-title":"Lactobacillus GG: Bacteriology and clinical applications","volume":"34","author":"Doron","year":"2005","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3920\/BM2011.0046","article-title":"Modulation of the murine microbiome with a concomitant anti-obesity effect by Lactobacillus rhamnosus GG and Lactobacillus sakei NR28","volume":"3","author":"Ji","year":"2012","journal-title":"Benef. Microbes."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.bbrc.2012.12.121","article-title":"Lactobacillus rhamnosus GG improves insulin sensitivity and reduces adiposity in high-fat diet-fed mice through enhancement of adiponectin production","volume":"431","author":"Kim","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.21315\/mjms2017.24.5.11","article-title":"Sample Size Calculation in Animal Studies Using Resource Equation Approach","volume":"24","author":"Arifin","year":"2017","journal-title":"Malays. J. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1097\/HJR.0b013e3281eacef1","article-title":"Running speed and maximal oxygen uptake in rats and mice: Practical implications for exercise training","volume":"14","author":"Kemi","year":"2007","journal-title":"Eur. J. Cardiovasc. Prev. Rehabil."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gould, T.D., Dao, D., and Kovacsics, C. (2009). Mood and Anxiety Related Phenotypes in Mice: Characterization Using Behavioral Tests, Human Press.","DOI":"10.1007\/978-1-60761-303-9"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1177\/0269881107073199","article-title":"The open field test: Reinventing the wheel","volume":"21","author":"Stanford","year":"2007","journal-title":"J. Psychopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16171","DOI":"10.1038\/srep16171","article-title":"MouseMove: An open source program for semi-automated analysis of movement and cognitive testing in rodents","volume":"5","author":"Samson","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1080\/1028415X.2018.1478653","article-title":"Apigenin reverses behavioural impairments and cognitive decline in kindled mice via CREB-BDNF upregulation in the hippocampus","volume":"23","author":"Sharma","year":"2020","journal-title":"Nutr. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0091-3057(95)00138-M","article-title":"Factor analysis of spatiotemporal and ethological measures in the murine elevated plus-maze test of anxiety","volume":"52","author":"Rodgers","year":"1995","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.lfs.2018.03.029","article-title":"Long term treadmill exercise performed to chronic social isolated rats regulate anxiety behavior without improving learning","volume":"200","author":"Cevik","year":"2018","journal-title":"Life. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.psyneuen.2016.03.007","article-title":"A diet high in fat and sugar reverses anxiety-like behaviour induced by limited nesting in male rats: Impacts on hippocampal markers","volume":"68","author":"Maniam","year":"2016","journal-title":"Psychoneuroendocrinology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1179\/1476830515Y.0000000034","article-title":"Western diet-induced anxiolytic effects in mice are associated with alterations in tryptophan metabolism","volume":"19","author":"Ohland","year":"2016","journal-title":"Nutr. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1080\/09637486.2019.1681380","article-title":"Degree of lipid saturation affects depressive-like behaviour and gut microbiota in mice","volume":"71","author":"Lee","year":"2020","journal-title":"Int. J. Food. Sci. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1038\/ijo.2010.34","article-title":"Chronic exposure to a high-fat diet affects stress axis function differentially in diet-induced obese and diet-resistant rats","volume":"34","author":"Shin","year":"2010","journal-title":"Int. J. Obes."},{"key":"ref_30","first-page":"1919","article-title":"Effects and HPA axis related mechanism of Kaixin-San and Danggui-Shaoyao-San on glucose and lipid metabolism in chronic stress rats with high-fat diet","volume":"38","author":"Wang","year":"2015","journal-title":"Zhong. Yao. Cai."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1146\/annurev-psych-010418-102936","article-title":"Stress and obesity","volume":"70","author":"Tomiyama","year":"2019","journal-title":"Annu. Rev. Psychol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1152\/japplphysiol.00467.2014","article-title":"Voluntary exercise improves metabolic profile in high-fat fed glucocorticoid-treated rats","volume":"118","author":"Beaudry","year":"2015","journal-title":"J. Appl. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.bbr.2016.05.051","article-title":"Corticosterone and dopamine D2\/D3 receptors mediate the motivation for voluntary wheel running in C57BL\/6J mice","volume":"311","author":"Ebada","year":"2016","journal-title":"Behav. Brain. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1111\/j.1365-2826.2010.02007.x","article-title":"Hypothalamic pituitary adrenal axis responses to low-intensity stressors are reduced after voluntary wheel running in rats","volume":"22","author":"Campeau","year":"2010","journal-title":"J. Neuroendocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.bbr.2008.07.036","article-title":"Voluntary exercise in C57 mice is anxiolytic across several measures of anxiety","volume":"197","author":"Salam","year":"2009","journal-title":"Behav. Brain. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.brainres.2004.05.086","article-title":"The effects of chronic treadmill and wheel running on behavior in rats","volume":"1019","author":"Burghardt","year":"2004","journal-title":"Brain. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1037\/0735-7044.120.4.787","article-title":"The role of voluntary exercise in enriched rearing: A behavioral analysis","volume":"120","author":"Pietropaolo","year":"2006","journal-title":"Behav. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbr.2016.04.051","article-title":"Voluntary wheel-running attenuates insulin and weight gain and affects anxiety-like behaviors in C57BL6\/J mice exposed to a high-fat diet","volume":"310","author":"Hicks","year":"2016","journal-title":"Behav. Brain. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.neubiorev.2014.12.017","article-title":"Is there a \u201cmetabolic-mood syndrome\u201d? A review of the relationship between obesity and mood disorders","volume":"52","author":"Mansur","year":"2015","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1053\/j.gastro.2014.01.058","article-title":"Diet and the intestinal microbiome: Associations, functions, and implications for health and disease","volume":"146","author":"Albenberg","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_41","unstructured":"Myles, E.M. (2019). Probiotic Effects on Adult Anxiety and Systemic Inflammation after Exposure to Western Diet, Dalhouse University."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1136\/gut.2006.117176","article-title":"Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation","volume":"56","author":"Gareau","year":"2007","journal-title":"Gut"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"138","DOI":"10.5056\/jnm16167","article-title":"Bifidobacterium longum and Lactobacillus helveticus synergistically suppress stress-related visceral hypersensitivity through hypothalamic-pituitary-adrenal axis modulation","volume":"24","author":"Payard","year":"2018","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"67","DOI":"10.12938\/bmfh.18-001","article-title":"Effects of Bifidobacterium breve B-3 on body fat reductions in pre-obese adults: A randomized, double-blind, placebo-controlled trial","volume":"37","author":"Minami","year":"2018","journal-title":"Biosci. Microbiota. Food Health"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Szuli\u0144ska, M., \u0141oniewski, I., Van Hemert, S., Sobieska, M., and Bogda\u0144ski, P. (2018). Dose-dependent effects of multispecies probiotic supplementation on the lipopolysaccharide (LPS) level and cardiometabolic profile in obese postmenopausal women: A 12-week randomized clinical trial. Nutrients, 10.","DOI":"10.3390\/nu10060773"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1097\/MPG.0b013e318263066c","article-title":"Probiotics to Adolescents With Obesity: Effects on Inflammation and Metabolic Syndrome","volume":"55","author":"Larsen","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1111\/ijpo.12273","article-title":"Probiotic supplementation increases obesity with no detectable effects on liver fat or gut microbiota in obese Hispanic adolescents: A 16-week, randomized, placebo-controlled trial","volume":"13","author":"Jones","year":"2018","journal-title":"Pediatr. Obes."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.micpath.2012.05.007","article-title":"Comparative meta-analysis of the effect of Lactobacillus species on weight gain in humans and animals","volume":"53","author":"Million","year":"2012","journal-title":"Microb. Pathog."},{"key":"ref_49","first-page":"8645","article-title":"Effect of probiotics on the occurrence of nutrition absorption capacities in healthy children: A randomized double-blinded placebo-controlled pilot study","volume":"23","author":"Ballini","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.exger.2018.12.005","article-title":"Exercise and probiotics attenuate the development of Alzheimer\u2019s disease in transgenic mice: Role of microbiome","volume":"115","author":"Abraham","year":"2019","journal-title":"Exp. Gerontol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/6\/1762\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:05:46Z","timestamp":1760162746000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/6\/1762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,21]]},"references-count":50,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["nu13061762"],"URL":"https:\/\/doi.org\/10.3390\/nu13061762","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,21]]}}}