title: Reciprocal influences between leptin and glucocorticoids during acute Trypanosoma cruzi infection.
abstract: Leptin and glucocorticoids (GCs) are involved in metabolic functions, thymic homeostasis and immune activity through complex interactions. We recently showed that C57BL/6 mice infected with Trypanosoma cruzi revealed a fatal disease associated with a dysregulated immune-endocrine response characterized by weight loss, deleterious synthesis of pro-inflammatory cytokines and GCs-driven thymus atrophy. Extending this study, we now explored the relationship between leptin and GCs, in terms of infection outcome, thymic and metabolic changes. T. cruzi-infected mice showed a food intake reduction, together with hypoglycemia and lipolysis-related changes. Infected animals also displayed a reduction in systemic and adipose tissue levels of leptin, paralleled by a down-regulation of their receptor (ObR) in the hypothalamus. Studies in infected mice subjected to adrenalectomy (Adx) showed a worsened course of infection accompanied by even more diminished systemic and intrathymic leptin levels, for which GCs are necessary not only to decrease inflammation but also to sustain leptin secretion. Adx also protected from thymic atrophy, independently of the reduced leptin contents. Leptin administration to infected mice aggravated inflammation, lowered parasite burden and attenuated GCs release, but did not normalize thymic atrophy or metabolic parameters. Acute T. cruzi infection in C57BL/6 mice coexists with a dysregulation of leptin/hypothalamic ObR circuitry dissociated from body weight and food intake control. Endogenous GCs production attempted to reestablish systemic leptin concentrations, but failed to improve leptin-protective activities at the thymic level, suggesting that the leptin/GCs intrathymic relationship is also altered during this infection.
authors.affiliation: Facultad de Ciencias Médicas, Instituto de Inmunología, Universidad Nacional de Rosario, Santa Fe 3100, 2000, Rosario, Argentina, romimanarin@gmail.com.
authors.forename: Romina
authors.initials: R
authors.lastname: Manarin
authors.forename: Silvina Raquel
authors.initials: SR
authors.lastname: Villar
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Fernández Bussy
authors.forename: Florencia Belén
authors.initials: FB
authors.lastname: González
authors.forename: Eva Verónica
authors.initials: EV
authors.lastname: Deschutter
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Bonantini
authors.forename: Eduardo
authors.initials: E
authors.lastname: Roggero
authors.forename: Ana Rosa
authors.initials: AR
authors.lastname: Pérez
authors.forename: Oscar
authors.initials: O
authors.lastname: Bottasso
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry; D000818:Animals; D001774:Blood Chemical Analysis; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology*; D005247:Feeding Behavior; D005938:Glucocorticoids / Q000378:metabolism*; D007003:Hypoglycemia; D007031:Hypothalamus / Q000737:chemistry; D007155:Immunologic Factors / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013950:Thymus Gland / Q000502:physiology; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D005938:Glucocorticoids; D007155:Immunologic Factors; D020738:Leptin