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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
Keywords: Lupus eritematós
Malalties autoimmunitàries
Malalties del fetge
Síndrome metabòlica
Proteïnes quinases
Ratolins (Animals de laboratori)
Lupus erythematosus
Autoimmune diseases
Liver diseases
Metabolic syndrome
Protein kinases
Mice (Laboratory animals)
Issue Date: 4-Dec-2012
Publisher: Public Library of Science (PLoS)
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.
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It is part of: PLoS One, 2012, vol. 7, num. 12, p. e51118
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

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