Autoimmune-mediated glucose intolerance in a mouse model of systemic lupus erythematosus.

Gabriel CL, Smith PB, Mendez-Fernandez YV, Wilhelm AJ, Ye AM, Major AS
Am J Physiol Endocrinol Metab. 2012 303 (11): E1313-24

PMID: 23032686 · PMCID: PMC3774080 · DOI:10.1152/ajpendo.00665.2011

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies against self-antigens such as double-stranded DNA and phospholipids. Classical comorbidities of SLE include glomerulonephritis, infection, cardiovascular disease, arthritis, skin disorders, and neurological disease. In addition to these classical comorbidities, there is emerging evidence that SLE patients are at higher risk of developing insulin resistance and other components of the metabolic syndrome. Visceral adipose tissue inflammation is a central mediator of insulin resistance in the obese setting, but the mechanism behind the pathogenesis of metabolic disease in the SLE patient population is unclear. We hypothesize that lupus-associated changes in the adaptive immune system are associated with disruption in glucose homeostasis in the context of SLE. To test this hypothesis, we assessed the metabolic and immunological phenotype of SLE-prone B6.SLE mice. B6.SLE mice fed a low-fat diet had significantly worsened glucose tolerance, increased adipose tissue insulin resistance, increased β-cell insulin secretion, and increased adipocyte size compared with their respective B6 controls. Independently of diet, B cells isolated from the white adipose tissue of B6.SLE mice were skewed toward IgG production, and the level of IgG1 was elevated in the serum of SLE-prone mice. These data show that B6.SLE mice develop defects in glucose homeostasis even when fed a low-fat diet and suggest that B cells may play a role in this metabolic dysfunction.

MeSH Terms (15)

Adaptive Immunity Adipocytes Adipose Tissue Analysis of Variance Animals B-Lymphocytes Disease Models, Animal Glucose Tolerance Test Homeostasis Insulin Insulin Resistance Lupus Erythematosus, Systemic Metabolic Syndrome Mice Mice, Inbred C57BL

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