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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Elucidating the role of leptin in systemic inflammation: a study targeting physiological leptin levels in rats and their macrophages

Texto completo
Flatow, Elizabeth A. [1] ; Komegae, Evilin N. [1] ; Fonseca, Monique T. [1] ; Brito, Camila F. [1] ; Musteata, Florin M. [2] ; Antunes-Rodrigues, Jose [3] ; Steiner, Alexandre A. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil
[2] Albany Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Albany, NY - USA
[3] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Physiol, Ribeirao Preto - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Citações Web of Science: 5

To elucidate the role of leptin in acute systemic inflammation, we investigated how its infusion at low, physiologically relevant doses affects the responses to bacterial lipopolysaccharide (LPS) in rats subjected to 24 h of food deprivation. Leptin was infused subcutaneously (0-20 mu g.kg(-1).h(-1)) or intracere-broventricularly (0-1 mu g.kg(-1).h(-1)). Using hypothermia and hypotension as biomarkers of systemic inflammation, we identified the phase extending from 90 to 240 min post-LPS as the most susceptible to modulation by leptin. In this phase, leptin suppressed the rise in plasma TNF-alpha and accelerated the recoveries from hypothermia and hypotension. Suppression of TNF-alpha was not accompanied by changes in other cytokines or prostaglandins. Leptin suppressed TNF-alpha when infused peripherally but not when infused into the brain. Importantly, the leptin dose that suppressed TNF-alpha corresponded to the lowest dose that limited food consumption; this dose elevated plasma leptin within the physiological range (to 5.9 ng/ml). We then conducted in vitro experiments to investigate whether an action of leptin on macrophages could parallel our in vivo observations. The results revealed that, when sensitized by food deprivation, LPS-stimulated peritoneal macrophages can be inhibited by leptin at concentrations that are lower than those reported to promote cytokine release. It is concluded that physiological levels of leptin do not exert a proinflammatory effect but rather an anti-inflammatory effect involving selective suppression of TNF-alpha via an action outside the brain. The mechanism of this effect might involve a previously unrecognized, suppressive action of leptin on macrophage subpopulations sensitized by food deprivation, but future studies are warranted. (AU)

Processo FAPESP: 12/03831-8 - Elo entre balanço energético e inflamação sistêmica: papel da leptina
Beneficiário:Alexandre Alarcon Steiner
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 13/09799-1 - Regulação da homeostase energética e do balanço hidromineral: das células aos sistemas fisiológicos
Beneficiário:José Antunes Rodrigues
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 16/04921-1 - Tônus arterial no choque séptico: uma nova vertente para um velho problema.
Beneficiário:Alexandre Alarcon Steiner
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 14/03719-9 - Papel da leptina na regulação da inflamação sistêmica
Beneficiário:Evilin Naname Komegae
Linha de fomento: Bolsas no Brasil - Pós-Doutorado