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Currently, no pharmacological treatments are available to treat NAFLD, and lifestyle modification, including dietary interventions, is the only remedy. Therefore, we conducted a study to determine whether supplementation with medium\u2010chain triglycerides (MCTs), containing a mixture of C8 and C10 (60\/40), attenuates NAFLD in obese and insulin\u2010resistant mice. To achieve that, we fed C57BL\/6 male mice a high\u2010fat diet (HFD) for 12 weeks to induce obesity and hepatic steatosis, after which obese mice were assigned randomly either to remain on the HFD or to transition to an HFD supplemented with MCTs (HFD + MCTs) or a low\u2010fat diet (LFD) for 6 weeks as another dietary intervention model. Another group of mice was kept on an LFD throughout the study and used as a lean control group. Obese mice that transitioned to HFD + MCTs exhibited improvement in glucose and insulin tolerance tests, and the latter improvement was independent of changes in adiposity when compared with HFD\u2010fed mice. Additionally, supplementation with MCTs significantly reduced hepatic steatosis, improved liver enzymes and decreased hepatic expression of inflammation\u2010related genes to levels similar to those observed in obese mice transitioned to an LFD. Importantly, HFD + MCTs markedly lowered hepatic ceramide and diacylglycerol content and prevented protein kinase\u00a0C\u2010\u03b5 translocation to the plasma membrane. Our study demonstrated that supplementation with MCTs formulated mainly from C8 and C10 effectively ameliorated NAFLD in obese mice.<\/jats:p>","DOI":"10.1113\/ep091545","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T08:08:53Z","timestamp":1704787733000},"page":"350-364","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A high\u2010fat diet supplemented with medium\u2010chain triglycerides ameliorates hepatic steatosis by reducing ceramide and diacylglycerol accumulation in mice"],"prefix":"10.1113","volume":"109","author":[{"given":"Stephanie","family":"Mourad","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Quebec Canada"},{"name":"Montreal Diabetes Research Center  Montr\u00e9al Quebec Canada"},{"name":"Cardiometabolic Health, Diabetes and Obesity Research Network  Montr\u00e9al Quebec 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