Involvement of cortisol and sirtuin1 during the response to stress of hypothalamic circadian system and food intake-related peptides in rainbow trout, Oncorhynchus mykiss

Abstract

ABSTRACTStress is conditioning animal welfare by negatively affecting a wide range of physiological and behavioral functions. This may be applied to circadian physiology and food intake. Cortisol, the stress-related hormone, may mediate such effect of stress, but other indirect mediators might be considered, such as sirtuin1. Then, either the independent modulatory effect or the existence of any interaction between mediators may be responsible. The circadian system is the main modulator of several integrative mechanisms at both central and peripheral levels that are rhythmically presented, thus influencing different processes such as food intake. In this way, food intake is controlled by the circadian system, as demonstrated by the persistence of such rhythms of food intake in the absence of environmental external cues. Our study aimed to evaluate the daily profile of hypothalamic mRNA abundance of circadian clock genes (clock1a, bmal1, per1 and rev-erbβ-like), and food intake regulators (crf, pomc-a1, cart, and npy) in rainbow trout (Oncorhynchus mykiss), the impact of stress on such rhythms, and the involvement of cortisol and sirtuin1 as mediators. Four cohorts of trout were subjected to 1) normal stocking density (control group), 2) high stocking density for 72 hours (stress group), 3) normal stocking density and implanted with mifepristone, a glucocorticoid receptors antagonist, and 4) mifepristone administered and stressed for 72 hours. Fish from each group were sampled every 4-h along the 24-h LD cycle, and cortisol, glucose and lactate plasma levels were evaluated. Hypothalamic mRNA abundance of clock genes, food intake regulators, glucocorticoid receptors and sirtuin1 were qPCR assayed. Our results reveal the impact of stress on most of the genes assayed, but different mechanisms appear to be involved. The rhythm of clock genes displayed decreased amplitude and averaged levels in stressed trout, with no changes of the acrophase being observed. This effect was not prevented by mifepristone. On the contrary, the effect of stress on the daily profile of crf, pomc-a1, and npy was totally prevented by mifepristone administration. Accordingly, cortisol appears to mainly mediate the effect of stress on food intake regulators through binding to specific glucocorticoid receptors within trout hypothalamus, whereas sirtuin1 is apparently mediating such effects on the circadian system in the same brain region. Further research must be performed to clarify those mechanisms through which stress influences food intake and the circadian oscillator within the same brain region, hypothalamus, in rainbow trout, and the interaction among them all.