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The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with important role not only in the regulation of inflammation, but also in the modulation of energy metabolism in the liver. Thus, the aim of this study was to investigate the role of <jats:italic>Mif<\/jats:italic> deficiency in fructose\u2010induced disturbances of hepatic lipid metabolism and ectopic lipid accumulation. Wild type (WT) and <jats:italic>Mif<\/jats:italic> deficient (MIF<jats:sup>\u2212\/\u2212<\/jats:sup>) C57Bl\/6J mice were used to analyze the effects of 9\u2010week 20% fructose\u2010enriched diet on hepatic lipid metabolism (both lipogenesis and \u03b2\u2010oxidation) and histology, inflammatory status and glucocorticoid receptor (GR) signaling. The results showed fructose\u2010induced elevation of lipogenic genes (fatty acid synthase (Fas) and stearoyl\u2010CoA desaturase\u20101 (Scd1) and transcriptional lipogenic regulators (liver X receptor (LXR), sterol regulatory element binding protein 1c (SREBP1c), and carbohydrate response element\u2010binding protein (ChREBP)). However, microvesicular fatty changes, accompanied with enhanced inflammation, were observable only in fructose\u2010fed <jats:italic>Mif<\/jats:italic> deficient animals, and were most likely result of GR activation and facilitated uptake and decreased \u03b2\u2010oxidation of FFA, as evidenced by elevated protein level of fatty acid translocase (FAT\/CD36) and decreased carnitine palmitoyl transferase 1 (CPT1) level. In conclusion, the results show that <jats:italic>Mif<\/jats:italic> deficiency aggravates the effects of energy\u2010rich fructose diet on hepatic lipid accumulation, most likely through enhanced inflammation and activation of GR signaling pathway.<\/jats:p>","DOI":"10.1002\/biof.1711","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T06:39:42Z","timestamp":1612161582000},"page":"363-375","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Macrophage migration inhibitory factor deficiency aggravates effects of fructose\u2010enriched diet on lipid metabolism in the mouse liver"],"prefix":"10.1002","volume":"47","author":[{"given":"Ljupka","family":"Gligorovska","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d \u2014 National Institute of Republic of Serbia University of Belgrade  Belgrade 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