Recombinant human leptin attenuates stress axis activity in common carp (Cyprinus carpio L.)

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SUMMARYAppetite suppression is a common response to hypoxia in fish that confers significant energy savings. Yet little is known about the endocrine signals involved in the regulation of food intake during chronic hypoxia. Thus, we assessed the impact of chronic hypoxia on food intake, the expression of the potent anorexigenic signal leptin and its receptor (lepr), the mRNA levels of key hypothalamic appetite-regulating genes, and the activity of the hypothalamic-pituitary-interrenal (HPI) axis in common carp, Cyprinus carpio. Fish exposed to 10% O 2 saturation for 8days were chronically anorexic and consumed on average 79% less food than normoxic controls. Hypoxia also elicited gradual and parallel increases in the expression of liver leptin-a-I, leptin-a-II, lepr and erythropoietin, a known hypoxia-responsive gene. In contrast, the liver mRNA levels of all four genes remained unchanged in normoxic fish pair-fed to the hypoxia treatment. In the hypothalamus, expression of the appetite-regulating genes were consistent with an inhibition and stimulation of hunger in the hypoxic and pair-fed fish, respectively, and reduced feed intake led to a decrease in lepr. Although both treatments elicited similar delayed increases in plasma cortisol, they were characterized by distinct HPI axis effector transcript levels and a marked differential increase in pituitary lepr expression. Together, these results show that a reduction in O 2 availability, and not feed intake, stimulates liver leptin-a expression in common carp and suggest that this pleiotropic cytokine is involved in the regulation of appetite and the endocrine stress response during chronic hypoxia.

Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 96%

Differential effects of chronic hypoxia and feed restriction on the expression of leptin and its receptor, food intake regulation and the endocrine stress response in common carp

Bernier

Gorissen

Flik

2012

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“…Undiluted plasma (in duplicate) was assayed using a radioimmunoassay (RIA) following the procedure described by Gorissen et al (2012). Intra-and inter-assay variations were 3.5% and 12.5%, respectively, and cross-reactivity of the cortisol antibody (antibody xm210; Abcam, Cambridge, UK) was as follows: cortisol 100%, 11-deoxycortisol 0.9%, prednisolone 5.6%, corticosterone 0.6%, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, testosterone, oestradiol and oestriol all <0.01%.…”

Section: Cortisol Radioimmunoassaymentioning

confidence: 99%

How do individuals cope with stress? Behavioural, physiological and neuronal differences between proactive and reactive coping styles in fish

Vindas

Gorissen

Höglund

et al. 2017

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Despite the use of fish models to study human mental disorders and dysfunctions, knowledge of regional telencephalic responses in nonmammalian vertebrates expressing alternative stress coping styles is poor. As perception of salient stimuli associated with stress coping in mammals is mainly under forebrain limbic control, we tested regionspecific forebrain neural (i.e. mRNA abundance and monoamine neurochemistry) and endocrine responses under basal and acute stress conditions for previously characterised proactive and reactive Atlantic salmon. Reactive fish showed a higher degree of the neurogenesis marker proliferating cell nuclear antigen ( pcna) and dopamine activity under basal conditions in the proposed hippocampus homologue (Dl) and higher post-stress plasma cortisol levels. Proactive fish displayed higher post-stress serotonergic signalling (i.e. higher serotonergic activity and expression of the 5-HT 1A receptor) in the proposed amygdala homologue (Dm), increased expression of the neuroplasticity marker brain-derived neurotropic factor (bdnf ) in both Dl and the lateral septum homologue (Vv), as well as increased expression of the corticotropin releasing factor 1 (crf 1 ) receptor in the Dl, in line with active coping neuro-profiles reported in the mammalian literature. We present novel evidence of proposed functional equivalences in the fish forebrain with mammalian limbic structures.

“…Plasma cortisol concentrations were quantified by radioimmunoassay (Gorissen et al, 2012) using a highly specific and sensitive commercially available antibody (xm210 cortisol antibody, Abcam, Cambridge, UK) and 3 H-cortisol (Perkin Elmer, Groningen, The Netherlands). The primary antibody shows a 100% cross-reactivity with cortisol, 0.9% with 11-deoxycortisol, 0.6% with corticosterone and <0.01% with 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, testosterone and oestradiol.…”

Section: Blood Analysesmentioning

confidence: 99%

“…Examples include suboptimal/poor water quality, repeated handling, transport and crowding. The effects of many of these challenges have been studied, albeit mostly as a single stressor (Barton and Peter, 1982;Gorissen et al, 2012;Di Marco et al, 2008;Pottinger, 2010;Remen et al, 2012). Studies on mammals (Aguilera and Rabadan-Diehl, 2000;Dhabhar and McEwen, 1997;Grissom and Bhatnagar, 2009;Thorsell et al, 1999), as well as fish (Schreck, 2000), show they have great resilience to a single stressor given repeatedly over long periods of time; however, knowledge on how ectotherms respond to multiple persistent stressors is very scant.…”

Section: Introductionmentioning

confidence: 99%

Stress in Atlantic salmon: response to unpredictable chronic stress

Madaro

Olsen

Kristiansen

et al. 2015

Combinations of stressors occur regularly throughout an animal's life, especially in agriculture and aquaculture settings. If an animal fails to acclimate to these stressors, stress becomes chronic, and a condition of allostatic overload arises with negative results for animal welfare. In the current study, we describe effects of exposing Atlantic salmon parr to an unpredictable chronic stressor (UCS) paradigm for 3 weeks. The paradigm involves exposure of fish to seven unpredictable stressors three times a day. At the end of the trial, experimental and control fish were challenged with yet another novel stressor and sampled before and 1 h after that challenge. Plasma cortisol decreased steadily over time in stressed fish, indicative of exhaustion of the endocrine stress axis. This was confirmed by a lower cortisol response to the novel stressor at the end of the stress period in chronically stressed fish compared with the control group. In the preoptic area (POA) and pituitary gland, chronic stress resulted in decreased gene expression of 11βhsd2, gr1 and gr2 in the POA and increased expression of those genes in the pituitary gland. POA crf expression and pituitary expression of pomcs and mr increased, whereas interrenal gene expression was unaffected. Exposure to the novel stressor had no effect on POA and interrenal gene expression. In the pituitary, crfr1, pomcs, 11βhsd2, grs and mr were downregulated. In summary, our results provide a novel overview of the dynamic changes that occur at every level of the hypothalamicpituitary gland-interrenal gland (HPI) axis as a result of chronic stress in Atlantic salmon.