Use this identifier to quote or link this document: http://hdl.handle.net/2072/227183

Metabolic alterations and increased liver mTOR expression precede the development of autoimmune disease in a murine model of lupus erythematosus
Vilà Prats, Laia; Roglans i Ribas, Núria; Baena, M.; Barroso Fernández, Emma; Alegret i Jordà, Marta; Merlos Roca, Manuel; Laguna Egea, Juan Carlos
Although metabolic syndrome (MS) and systemic lupus erythematosus (SLE) are often associated, a common link has not been identified. Using the BWF1 mouse, which develops MS and SLE, we sought a molecular connection to explain the prevalence of these two diseases in the same individuals. We determined SLE- markers (plasma anti-ds-DNA antibodies, splenic regulatory T cells (Tregs) and cytokines, proteinuria and renal histology) and MS-markers (plasma glucose, non-esterified fatty acids, triglycerides, insulin and leptin, liver triglycerides, visceral adipose tissue, liver and adipose tissue expression of 86 insulin signaling-related genes) in 8-, 16-, 24-, and 36-week old BWF1 and control New-Zealand-White female mice. Up to week 16, BWF1 mice showed MS-markers (hyperleptinemia, hyperinsulinemia, fatty liver and visceral adipose tissue) that disappeared at week 36, when plasma anti-dsDNA antibodies, lupus nephritis and a pro-autoimmune cytokine profile were detected. BWF1 mice had hyperleptinemia and high splenic Tregs till week 16, thereby pointing to leptin resistance, as confirmed by the lack of increased liver P-Tyr-STAT-3. Hyperinsulinemia was associated with a down-regulation of insulin related-genes only in adipose tissue, whereas expression of liver mammalian target of rapamicyn (mTOR) was increased. Although leptin resistance presented early in BWF1 mice can slow-down the progression of autoimmunity, our results suggest that sustained insulin stimulation of organs, such as liver and probably kidneys, facilitates the over-expression and activity of mTOR and the development of SLE.
2014-03-25
Lupus eritematós
Malalties autoimmunitàries
Malalties del fetge
Síndrome metabòlica
Proteïnes quinases
Citoquines
Ratolins (Animals de laboratori)
Lupus erythematosus
Autoimmune diseases
Liver diseases
Metabolic syndrome
Protein kinases
Cytokines
Mice (Laboratory animals)
cc-by (c) Vilà Prats, Laia et al., 2012
http://creativecommons.org/licenses/by/3.0/es
Article
info:eu-repo/semantics/publishedVersion
Public Library of Science (PLoS)
         

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