title: Systemic lupus erythematosus onset in lupus-prone B6.MRL/lpr mice Is influenced by weight gain and Is preceded by an increase in neutrophil oxidative burst activity.
abstract: In this study, we assessed whether weight gain influenced the systemic lupus erythematosus (SLE) onset and/or outcome, and examined the role that reactive oxygen species (ROS) production by neutrophils played in the SLE onset and/or outcome. Female control (C57BL/6) and lupus-prone B6.MRL/lpr mice (CM and LPM, respectively) at 4 weeks old were fed standard diet or standard diet plus cafeteria diet during 12 weeks. SLE diagnosis relied on the presence of both antinuclear antibodies (ANA) and renal abnormalities. We found that the percentage of weight gain in CM and LPM increased as a function of the length of cafeteria diet feeding period, but it was not associated with energy intake. Cafeteria diet-fed CM and LPM at 8 and 12 weeks old were overweight, while CM and LPM at 16 weeks old were obese. Compared with standard diet-fed CM and LPM, cafeteria diet-fed CM and LPM exhibited elevated glucose and total cholesterol levels, and diminished triglycerides levels. Standard diet-fed 16-week-old LPM and cafeteria diet-fed 12-week-old LPM had nephritis, characterized by the increased interstitial infiltration of leukocytes. Cafeteria diet-induced weight gain rose the frequency of homogeneous and speckled ANA staining patterns in the 12- and 16-week-old LPM groups. Together, these results indicated that weight gain anticipated the SLE onset. In addition, neutrophils from cafeteria diet-fed 8-week-old LPM exhibited augmented ROS production capacity; in standard diet-fed LPM, such rise occurred only in the 16-week-old group. Thus, the neutrophil ROS production capacity was increased before the SLE onset and during its outcome. Overweight and obese CM and LPM displayed elevated levels of kidney, liver, heart, and spleen lipid peroxidation. In conclusion, cafeteria diet-induced weight gain is associated with the increased production of ANA and neutrophil-derived ROS, which may contribute to accelerate the SLE onset.
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, Ribeirão Preto, SP 14049-900, Brazil.
authors.forename: Juliana Escher
authors.initials: JE
authors.lastname: Toller-Kawahisa
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, Ribeirão Preto, SP 14040-903, Brazil.
authors.forename: Nathália Cristina
authors.initials: NC
authors.lastname: Canicoba
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, Ribeirão Preto, SP 14040-903, Brazil.
authors.forename: Vinicius Paula
authors.initials: VP
authors.lastname: Venancio
authors.affiliation: Graduação em Fisioterapia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, Ribeirão Preto, SP 14049-900, Brazil.
authors.forename: Rogério
authors.initials: R
authors.lastname: Kawahisa
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, Ribeirão Preto, SP 14040-903, Brazil.
authors.forename: Lusânia Maria Greggi
authors.initials: LM
authors.lastname: Antunes
authors.affiliation: Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, Ribeirão Preto, SP 14049-900, Brazil.
authors.forename: Thiago Mattar
authors.initials: TM
authors.lastname: Cunha
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, Ribeirão Preto, SP 14040-903, Brazil. Electronic address: clenimar@usp.br.
authors.forename: Cleni Mara
authors.initials: CM
authors.lastname: Marzocchi-Machado
mesh_terms: D017668:Age of Onset; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D066273:Diet, Western / Q000009:adverse effects; D005260:Female; D007668:Kidney / Q000473:pathology; D015227:Lipid Peroxidation; D008099:Liver / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D009504:Neutrophils / Q000378:metabolism*; D018384:Oxidative Stress; D016897:Respiratory Burst; D015430:Weight Gain
chemical_list: D000974:Antibodies, Antinuclear
keywords: Antinuclear antibody; Neutrophil; Obesity; Oxidative stress; Reactive oxygen species; Systemic lupus erythematosus