RESUMO
AIM: Dietary restriction (DR) and fasting (FA) induce robust protection against the detrimental effects of renal ischemia-reperfusion injury (I/RI). Several mechanisms of protection have been proposed, such as hormesis. Hormesis is defined as a life-supporting beneficial effect resulting from the cellular responses to single or multiple rounds of (mild) stress. The cold exposure (CE) model is a stress model similar to DR, and has been shown to have hormetic effects and has proved to increase longevity. CE is considered to be the most robust method to increase metabolism through activation of brown adipocytes. BAT has been considered important in etiology of obesity and its metabolic consequences. MATERIALS AND METHODS: Since DR, FA, and CE models are proposed to work through hormesis, we investigated physiology of adipose tissue and effect on BAT in these models and compared them to ad libitum (AL) fed mice. We also studied the differential effect of these stress models on immunological changes, and effect of CE on renal I/RI. KEY FINDINGS: We show similar physiological changes in adiposity in male C57Bl/6 mice due to DR, FA and CE, but the CE mice were not protected against renal I/RI. The immunophenotypic changes observed in the CE mice were similar to the AL animals, in contrast to FA mice, that showed major immunophenotypic changes in the B and T cell development stages in primary and secondary lymphoid organs. SIGNIFICANCE: Our findings thus demonstrate that DR, FA and CE are hormetic stress models. DR and FA protect against renal I/IR, whereas CE could not.
Assuntos
Temperatura Baixa , Dieta , Hormese , Nefropatias/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Adipócitos Marrons/fisiologia , Animais , Restrição Calórica , Corticosterona/sangue , Jejum , Expressão Gênica , Canais Iônicos/biossíntese , Canais Iônicos/genética , Nefropatias/fisiopatologia , Longevidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/biossíntese , Proteínas Mitocondriais/genética , Estresse Oxidativo , Traumatismo por Reperfusão/fisiopatologia , Estresse Fisiológico , Linfócitos T/fisiologia , Proteína Desacopladora 1RESUMO
Preoperative fasting and dietary restriction offer robust protection against renal ischemia/reperfusion injury (I/RI) in mice. We recently showed that Mannan-binding lectin (MBL), the initiator of the lectin pathway of complement activation, plays a pivotal role in renal I/RI. Based on these findings, we investigated the effect of short-term DR (30% reduction of total food intake) or three days of water only fasting on MBL in 10-12 weeks old male C57/Bl6 mice. Both dietary regimens significantly reduce the circulating levels of MBL as well as its mRNA expression in liver, the sole production site of MBL. Reconstitution of MBL abolished the protection afforded by dietary restriction, whereas in the fasting group the protection persisted. These data show that modulation of MBL is involved in the protection against renal I/RI induced by dietary restriction, and suggest that the mechanisms of protection induced by dietary restriction and fasting may be different.
Assuntos
Restrição Calórica , Regulação da Expressão Gênica , Nefropatias/prevenção & controle , Fígado/metabolismo , Lectina de Ligação a Manose/biossíntese , Traumatismo por Reperfusão/prevenção & controle , Animais , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Fígado/patologia , Masculino , Camundongos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
Dietary restriction (DR) delays ageing and extends life span. Both long- and short-term DR, as well as short-term fasting provide robust protection against many "neuronal and surgery related damaging phenomena" such as Parkinson's disease and ischemia-reperfusion injury. The exact mechanism behind this phenomenon has not yet been elucidated. Its anti-inflammatory actions prompted us to thoroughly investigate the consequences of DR and fasting on B and T cell compartments in primary and secondary lymphoid organs of male C57Bl/6 mice. In BM we found that DR and fasting cause a decrease in the total B cell population and arrest early B cell development, while increasing the number of recirculating mature B cells. In the fasting group, a significant reduction in peripheral B cell counts was observed in both spleen and mesenteric lymph nodes (mLN). Thymopoiesis was arrested significantly at double negative DN2 stage due to fasting, whereas DR resulted in a partial arrest of thymocyte development at the DN4 stage. Mature CD3(+) T cell populations were increased in BM and decreased in both spleen and mLN. Thus, DR arrests B cell development in the BM but increases the number of recirculating mature B cells. DR also arrests maturation of T cells in thymus, resulting in depletion of mature T cells from spleen and mLN while recruiting them to the BM. The functional relevance in relation to protection against organ damage needs to be determined.