{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:42:57Z","timestamp":1791474177811,"version":"4.3.4"},"reference-count":205,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T00:00:00Z","timestamp":1720828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases","award":["R21 DK128678"],"award-info":[{"award-number":["R21 DK128678"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Elevations in fructose consumption have been reported to contribute significantly to an increased incidence of obesity and metabolic diseases in industrial countries. Mechanistically, a high fructose intake leads to the dysregulation of glucose, triglyceride, and cholesterol metabolism in the liver, and causes elevations in inflammation and drives the progression of nonalcoholic fatty liver disease (NAFLD). A high fructose consumption is considered to be toxic to the body, and there are ongoing measures to develop pharmaceutical therapies targeting fructose metabolism. Although a large amount of work has summarized the effects fructose exposure within the intestine, liver, and kidney, there remains a gap in our knowledge regarding how fructose both indirectly and directly influences immune cell recruitment, activation, and function in metabolic tissues, which are essential to tissue and systemic inflammation. The most recent literature demonstrates that direct fructose exposure regulates oxidative metabolism in macrophages, leading to inflammation. The present review highlights (1) the mechanisms by which fructose metabolism impacts crosstalk between tissues, nonparenchymal cells, microbes, and immune cells; (2) the direct impact of fructose on immune cell metabolism and function; and (3) therapeutic targets of fructose metabolism to treat NAFLD. In addition, the review highlights how fructose disrupts liver tissue homeostasis and identifies new therapeutic targets for treating NAFLD and obesity.<\/jats:p>","DOI":"10.3390\/biom14070845","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T18:17:32Z","timestamp":1721067452000},"page":"845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Regulation of Fructose Metabolism in Nonalcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Mareca","family":"Lodge","sequence":"first","affiliation":[{"name":"Department of Molecular and Structural Biochemistry, North Carolina State University, 128 Polk Hall Campus, Box 7622, Raleigh, NC 27695, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Dykes","sequence":"additional","affiliation":[{"name":"Department of Molecular and Structural Biochemistry, North Carolina State University, 128 Polk Hall Campus, Box 7622, Raleigh, NC 27695, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arion","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Molecular and Structural Biochemistry, North Carolina State University, 128 Polk Hall Campus, Box 7622, Raleigh, NC 27695, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","article-title":"The prevalence and incidence of NAFLD worldwide: A systematic review and meta-analysis","volume":"7","author":"Riazi","year":"2022","journal-title":"Lancet Gastroenterol. 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