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Additionally, the administration of a KD prior to alcohol exposure (i.e., a history of KD) reduced alcohol consumption in alcohol-dependent rats that were no longer on the diet. In the present study, we investigated the mechanisms by which a KD alters alcohol metabolism and tested whether ongoing KD exposure reduces alcohol consumption in rats. We hypothesized that chronic KD exposure alters hepatic alcohol-metabolizing enzymes, slows alcohol metabolism, and reduces alcohol self-administration in alcohol-dependent rats. We found that male and female rats maintained on a KD had higher blood alcohol levels, lower hepatic alcohol dehydrogenase 1 protein levels, and a higher nicotinamide adenine dinucleotide [NAD+]\/[NADH] ratio in the liver cytoplasm compared with chow-fed control rats. Furthermore, KD-fed rats demonstrated lower brain glucose uptake relative to chow-fed control rats. In a model of alcohol dependence, the KD reduced alcohol consumption in male, but not female, rats compared with chow-fed rats. These findings suggest that a KD alters brain energetics and alcohol metabolism, which may contribute to reduced alcohol consumption in male rats.<\/jats:p>","DOI":"10.1038\/s41386-026-02383-5","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T15:07:35Z","timestamp":1774019255000},"page":"1568-1576","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A ketogenic diet reduces hepatic alcohol metabolism and alcohol consumption in rats"],"prefix":"10.1038","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1049-1523","authenticated-orcid":false,"given":"Sophie K.","family":"Elvig","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne","family":"McGinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3136-4811","authenticated-orcid":false,"given":"Xinyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janaina C. 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