title: Tissue-specific regulation of inflammation by macrophage migration inhibitory factor and glucocorticoids in fructose-fed Wistar rats.
abstract: High fructose consumption is commonly associated with insulin resistance, disturbed glucose homeostasis and low-grade inflammation. Increased glucocorticoid production within adipose tissue has been implicated in the pathogenesis of fructose-induced metabolic syndrome. Immunosuppressive actions of glucocorticoids can be counter-regulated by macrophage migration inhibitory factor (MIF), which is recognised as a key molecule in metabolic inflammation. In the present study, we hypothesised that coordinated action of glucocorticoids and MIF can mediate the effects of a high-fructose diet on adipose tissue and liver inflammation. We examined the effects of long-term consumption of a 10% fructose solution on corticosterone (CORT) and MIF levels in rat blood plasma, liver and adipose tissue, as well as MIF and TNF-a mRNA expression and NF-kB activation in the same tissues. The high-fructose diet led to an increase in both CORT and MIF in the adipose tissue, and a highly significant positive correlation between their levels was observed. The attenuated NF-kB activation and unaltered TNF-a mRNA expression noticed in the adipose tissue could be interpreted as an outcome of the opposing actions of CORT and MIF. In contrast to adipose tissue, inflammation in the liver was characterised by NF-kB activation, an increased TNF-a mRNA level and unchanged levels of MIF protein, MIF mRNA and CORT. Overall, these findings suggest that a high-fructose diet differently affects the levels of glucocorticoids and MIF in the adipose tissue and liver, implicating that fructose over-consumption has tissue-specific effects on regulation of metabolic inflammation.
authors.affiliation: Department of Biochemistry, Institute for Biological Research Siniša Stanković, University of Belgrade, 142 Despot Stefan Boulevard, 11000 Belgrade, Serbia. nvelickovic@ibiss.bg.ac.rs
authors.forename: Nataša
authors.initials: N
authors.lastname: Veličković
authors.forename: Ana
authors.initials: A
authors.lastname: Djordjevic
authors.forename: Ana
authors.initials: A
authors.lastname: Vasiljević
authors.forename: Biljana
authors.initials: B
authors.lastname: Bursać
authors.forename: Danijela Vojnović
authors.initials: DV
authors.lastname: Milutinović
authors.forename: Gordana
authors.initials: G
authors.lastname: Matić
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D004032:Diet / Q000009:adverse effects*; D019422:Dietary Sucrose / Q000009:adverse effects; D005632:Fructose / Q000009:adverse effects*; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D039841:Leukocyte L1 Antigen Complex / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D019422:Dietary Sucrose; D039841:Leukocyte L1 Antigen Complex; D008263:Macrophage Migration-Inhibitory Factors; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005632:Fructose; D003345:Corticosterone