Ghrelin modulates hypothalamic fatty acid-sensing and control of food intake in rainbow trout

Abstract

There is no information available on fish as far as the possible effects of ghrelin on hypothalamic fatty acid metabolism and the response of fatty acid-sensing systems, which are involved in the control of food intake. Therefore, we assessed in rainbow trout the response of food intake, hypothalamic fatty acid-sensing mechanisms and expression of neuropeptides involved in the control of food intake to the central treatment of ghrelin in the presence or absence of a long-chain fatty acid such as oleate. We observed that the orexigenic actions of ghrelin in rainbow trout are associated with changes in fatty acid metabolism in the hypothalamus and an inhibition of fatty acid-sensing mechanisms, which ultimately lead to changes in the expression of anorexigenic and orexigenic peptides resulting in increased orexigenic potential and food intake. Moreover, the response to increased levels of oleate of hypothalamic fatty acid-sensing systems (activation), expression of neuropeptides (enhanced anorexigenic potential) and food intake (decrease) were counteracted by the simultaneous treatment with ghrelin. These changes provide evidence for the first time in fish of a possible modulatory role of ghrelin on the metabolic regulation by fatty acid of food intake occurring in the hypothalamus.

Ceramide counteracts the effects of ghrelin on the metabolic control of food intake in rainbow trout

“…These changes support the activation of fatty acid-sensing systems by GHRL treatment, and most of them are in agreement with a previous study carried out in the same species under similar experimental conditions (Velasco et al, 2016a). The activation of these systems is also in agreement with the increased orexigenic potential observed simultaneously, as supported by decreased mRNA abundance of POMC and CART and increased mRNA abundance of NPY and AgRP, in a way comparable to that reported in mammals (Ramírez et al, 2013).…”

“…Moreover, GHRL is also involved in the control of glucose and lipid metabolism in fish (Kaiya et al, 2009;Salmerón et al, 2015). In a previous study in rainbow trout, we demonstrated that intracerebroventricular (ICV) GHRL treatment counteracts the effects in hypothalamus of raised levels of a LCFA-like oleate on the activity of fatty acid-sensing systems, the expression of neuropeptides and food intake (Velasco et al, 2016a).…”

“…In previous studies in fish, we demonstrated that in rainbow trout (Librán-Pérez et al, 2012, 2013, 2014Velasco et al, 2016a) and Senegalese sole (Conde-Sieira et al, 2015) the hypothalamus detects changes in the levels of specific long-chain fatty acids (LCFAs) through fatty acid-sensing mechanisms. A schematic drawing summarizing five main fatty acid-sensing systems in fish including the enzymes involved (Soengas, 2014;Conde-Sieira and Soengas, 2017) and their effects on food intake is shown in Fig.…”

“…This response is mediated by changes in fatty acid-sensing systems and neuropeptide expression, reversing changes elicited by raised LCFA levels (Sangiao-Alvarellos et al, 2010;Velásquez et al, 2011;Stark et al, 2015). In fish, GHRL is clearly involved in the control of food intake as an orexigenic factor, as demonstrated in several fish species (Unniappan et al, 2002;Kang et al, 2011;Jönsson, 2013) including rainbow trout (Velasco et al, 2016a). However, other studies suggested an anorexigenic effect of GHRL in rainbow trout (Jönsson et al, 2007(Jönsson et al, , 2010, which could relate to the different time period assessed (1 versus 6-24 h) as well as the increased mRNA abundance of corticotropin-releasing factor observed by Jönsson et al (2010).…”

“…These mechanisms are, in general, comparable to those described in mammals (Blouet and Schwartz, 2010;Lipina et al, 2014;Morton et al, 2014;Magnan et al, 2015) with the notable exception of the ability of fish systems to detect changes in the levels of not only LCFAs but also mediumchain fatty acids like octanoate (rainbow trout) and polyunsaturated fatty acids like α-linolenate (Senegalese sole). The activation of these systems results in an increase in the anorexigenic potential (balance between mRNA abundance of anorexigenic and orexigenic neuropeptides) through increased production of the anorexigenic peptides pro-opio melanocortin (POMC) and cocaine-and amphetamine-related transcript (CART) and decreased production of the orexigenic peptides neuropeptide Y (NPY) and agouti-related peptide (AgRP), ultimately leading to decreased food intake (Librán-Pérez et al, 2012, 2014Velasco et al, 2016a).…”