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Title:	Metabolic alterations and increased liver mTOR expression precede the development of autoimmune disease in a murine model of lupus erythematosus
Author:	Vilà Prats, Laia; Roglans i Ribas, Núria; Baena Muñoz, Miguel; Barroso Fernández, Emma; Alegret i Jordà, Marta; Merlos Roca, Manuel; Laguna Egea, Juan Carlos
Other authors:	Universitat de Barcelona
Abstract:	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.
Subject(s):	-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)
Rights:	cc-by (c) Vilà Prats, Laia et al., 2012 http://creativecommons.org/licenses/by/3.0/es
Document type:	Article Article - Published version
Published by:	Public Library of Science (PLoS)
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