{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:23:43Z","timestamp":1788920623114,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Antipsychotic (AP) medications, such as olanzapine (OLZ), are used in the treatment of schizophrenia and a growing number of \u2018off\u2010label\u2019 conditions. A single dose of OLZ causes robust increases in blood glucose within minutes of treatment. The purpose of the current study was to investigate whether interventions that increase circulating ketone bodies (fasting, \u03b2\u2010hydroxybutyrate (\u03b2HB), ketone esters or a ketogenic diet (KD)) would be sufficient to protect against the acute metabolic side effects of OLZ. We demonstrate that fasting or the short\u2010term consumption of a KD protects against OLZ\u2010induced hyperglycaemia, independent of alterations in whole\u2010body insulin action, and in parallel with a blunted rise in serum glucagon. Interestingly, the effects of fasting and KDs were not recapitulated by acutely increasing circulating concentrations of ketone bodies through treatment with \u03b2HB or oral ketone esters, approaches which increase ketone bodies to physiological or supra\u2010physiological levels, respectively. Collectively, our findings demonstrate that fasting and the short\u2010term consumption of a KD can protect against acute AP\u2010induced perturbations in glucose homeostasis, whereas manipulations which acutely increase circulating ketone bodies do not elicit the same beneficial effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Antipsychotic medications cause rapid and robust increases in blood glucose.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Co\u2010treatment approaches to offset these harmful metabolic side effects have not been identified.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We demonstrate that fasting or the consumption of a short\u2010term ketogenic diet, but not treatment with \u03b2\u2010hydroxybutyrate or oral ketone esters, protects against acute antipsychotic\u2010induced hyperglycaemia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The protective effects of fasting and ketogenic diets were paralleled by reductions in serum glucagon, but not improvements in whole\u2010body insulin action.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp282922","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T18:08:17Z","timestamp":1651687697000},"page":"2713-2728","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Fasting or the short\u2010term consumption of a ketogenic diet protects against antipsychotic\u2010induced hyperglycaemia in mice"],"prefix":"10.1113","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6518-3800","authenticated-orcid":false,"given":"Hesham","family":"Shamshoum","sequence":"first","affiliation":[{"name":"Department of Human Health and Nutritional Sciences University of Guelph  Guelph Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5176-3524","authenticated-orcid":false,"given":"Kyle D.","family":"Medak","sequence":"additional","affiliation":[{"name":"Department of Human Health and Nutritional Sciences University of Guelph  Guelph Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6469-0747","authenticated-orcid":false,"given":"Greg L.","family":"McKie","sequence":"additional","affiliation":[{"name":"Department of Human Health and Nutritional Sciences University of Guelph  Guelph Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret K.","family":"Hahn","sequence":"additional","affiliation":[{"name":"Centre for Addiction and Mental Health  Toronto Ontario Canada"},{"name":"Department of Psychiatry University of Toronto  Toronto Ontario Canada"},{"name":"Banting and Best Diabetes Centre University of Toronto  Ontario Canada"},{"name":"Department of Pharmacology and Toxicology University of Toronto  Toronto Ontario Canada"},{"name":"Institute of Medical Science University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3867-8901","authenticated-orcid":false,"given":"David C.","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Human Health and Nutritional Sciences University of Guelph  Guelph Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbq053"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2008.05.003"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.05.002"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2020.1713091"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1139\/y59-099"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.110140"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.05.035"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.118.248393"},{"key":"e_1_2_5_10_1","first-page":"e190013","article-title":"Preclinical and clinical sex differences in antipsychotic\u2010induced metabolic disturbances: A narrative review of adiposity and glucose metabolism","volume":"4","author":"Castellani L. 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