scholarly journals Hypothalamic mechanisms linking fatty acid sensing and food intake regulation in rainbow trout

2017 ◽  
Vol 59 (4) ◽  
pp. 377-390 ◽  
Author(s):  
Cristina Velasco ◽  
Cristina Otero-Rodiño ◽  
Sara Comesaña ◽  
Jesús M Míguez ◽  
José L Soengas

We assessed in rainbow trout hypothalamus the effects of oleate and octanoate on levels and phosphorylation status of two transcription factors, FoxO1 and CREB, possibly involved in linking activation of fatty acid sensing with modulation of food intake through the expression of brain neuropeptides. Moreover, we assessed changes in the phosphorylation status of three proteins possibly involved in modulation of these transcription factors such as Akt, AMPK and mTOR. In a first experiment, we evaluated, in pools of hypothalamus incubated for 3 h and 6 h at 15°C in a modified Hanks’ medium containing 100 or 500 µM oleate or octanoate, the response of fatty acid sensing, neuropeptide expression and phosphorylation status of proteins of interest. The activation of fatty acid sensing and enhanced anorectic potential occurred in parallel with the activation of Akt and mTOR, and the inhibition of AMPK. The changes in these proteins would relate to a neuropeptide expression through changes in the phosphorylation status of transcription factors under their control, such as CREB and FoxO1, which displayed inhibitory (CREB) or activatory (FoxO1) responses when tissues were incubated with oleate or octanoate. In a second experiment, we incubated hypothalamus for 6 h with 500 µM oleate or octanoate alone or in the presence of specific inhibitors of Akt, AMPK, mTOR, CREB or FoxO1. The presence of inhibitors counteracted the effects of oleate or octanoate on the phosphorylation status of the proteins of interest. The results support, for the first time in fish, the involvement of these proteins in the regulation of food intake by fatty acids.

2019 ◽  
Vol 62 (3) ◽  
pp. 101-116
Author(s):  
Cristina Velasco ◽  
Sara Comesaña ◽  
Marta Conde-Sieira ◽  
Jesús M Míguez ◽  
José L Soengas

We hypothesize that cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) are involved in the modulation of metabolic regulation of food intake by fatty acids in fish. Therefore, we assessed in rainbow trout (Oncorhynchus mykiss) the effects of intracerebroventricular treatment with 1 ng/g of CCK-8 and with 2 ng/g of GLP-1 on food intake, expression of neuropeptides involved in food intake control and the activity of fatty acid-sensing systems in hypothalamus and hindbrain. Food intake decreased up to 24 h post-treatment to 49.8–72.3% and 3.1–17.8% for CCK-8 and GLP-1, respectively. These anorectic responses are associated with changes in fatty acid metabolism and an activation of fatty acid-sensing mechanisms in the hypothalamus and hindbrain. These changes occurred in parallel with those in the expression of anorexigenic and orexigenic peptides. Moreover, we observed that the activation of fatty acid sensing and the enhanced anorectic potential elicited by CCK-8 and GLP-1 treatments occurred in parallel with the activation of mTOR and FoxO1 and the inhibition of AMPKα, BSX and CREB. The results are discussed in the context of metabolic regulation of food intake in fish.


2020 ◽  
Vol 223 (17) ◽  
pp. jeb227330
Author(s):  
Cristina Velasco ◽  
Marta Conde-Sieira ◽  
Sara Comesaña ◽  
Mauro Chivite ◽  
Adrián Díaz-Rúa ◽  
...  

ABSTRACTWe hypothesized that the free fatty acid receptors FFA1 and FFA4 might be involved in the anorectic response observed in fish after rising levels of long-chain fatty acids (LCFAs) such as oleate. In one experiment we demonstrated that intracerebroventricular (i.c.v.) treatment of rainbow trout with FFA1 and FFA4 agonists elicited an anorectic response 2, 6 and 24 h after treatment. In a second experiment, the same i.c.v. treatment resulted after 2 h in an enhancement in the mRNA abundance of anorexigenic neuropeptides pomca1 and cartpt and a decrease in the values of orexigenic peptides npy and agrp1. These changes occurred in parallel with those observed in the mRNA abundance and/or protein levels of the transcription factors Creb, Bsx and FoxO1, protein levels and phosphorylation status of Ampkα and Akt, and mRNA abundance of plcb1 and itrp3. Finally, we assessed in a third experiment the response of all these parameters after 2 h of i.c.v. treatment with oleate (the endogenous ligand of both free fatty acid receptors) alone or in the presence of FFA1 and FFA4 antagonists. Most effects of oleate disappeared in the presence of FFA1 and FFA4 antagonists. The evidence obtained supports the involvement of FFA1 and FFA4 in fatty acid sensing in fish brain, and thus involvement in food intake regulation through mechanisms not exactly comparable (differential response of neuropeptides and cellular signalling) to those known in mammals.


2014 ◽  
Vol 129 ◽  
pp. 272-279 ◽  
Author(s):  
Marta Librán-Pérez ◽  
Cristina Otero-Rodiño ◽  
Marcos A. López-Patiño ◽  
Jesús M. Míguez ◽  
José L. Soengas

Author(s):  
Cristina Velasco ◽  
Marta Conde-Sieira ◽  
Sara Comesaña ◽  
Mauro Chivite ◽  
Jesús M. Míguez ◽  
...  

We evaluated the role of GPR84 and GPR119 in food intake regulation in fish using rainbow trout (Oncorhynchus mykiss) as a model. In a first experiment, we assessed the effects on food intake of intracerebroventricular treatment with agonists of these receptors. In a second experiment, we assessed in hypothalamus and hindbrain the impact of the same treatments on mRNA abundance of neuropeptides involved in the metabolic control of food intake (npy, agrp1, pomca1, and cartpt) as well as in changes in parameters related to signalling pathways and transcription factors involved in the integrative response leading to neuropeptide production. Treatment with both agonists elicited an anorectic response in rainbow trout attributable to changes observed in the mRNA abundance of the four neuropeptides. Changes in neuropeptides relate to changes observed in mRNA abundance and phosphorylation status of the transcription factor Foxo1. These changes occurred in parallel with changes in phosphorylation status of Ampkα and Akt, mRNA abundance of mTOR as well as in signalling pathways related to PLCβ and IP3. These results allow us to suggest that 1) at least part of the capacity of fish brain to sense MCFA like octanoate depends on the function of GPR84, and 2) the capacity of fish brain to sense NAE or triglyceride-derived molecules through binding of these ligands to GPR119.


2012 ◽  
Vol 302 (11) ◽  
pp. R1340-R1350 ◽  
Author(s):  
Marta Librán-Pérez ◽  
Sergio Polakof ◽  
Marcos A. López-Patiño ◽  
Jesús M. Míguez ◽  
José L. Soengas

Enhanced lipid levels inhibit food intake in fish but no studies have characterized the possible mechanisms involved. We hypothesize that the presence of fatty acid (FA)-sensing mechanisms could be related to the control of food intake. Accordingly, we evaluated in the hypothalamus, hindbrain, and Brockmann bodies (BB) of rainbow trout changes in parameters related to fatty acid metabolism, transport of FA, nuclear receptors, and transcription factors involved in lipid metabolism, and components of the KATP channel after intraperitoneal administration of different doses of oleic acid (long-chain fatty acid, LCFA) or octanoic acid (medium-chain fatty acid, MCFA). The increase in circulating LCFA or MCFA levels elicited an inhibition in food intake and induced in the hypothalamus a response compatible with fatty acid sensing in which fatty acid metabolism, binding to cluster of differentiation 36 (CD36), and mitochondrial activity are apparently involved, which is similar to that suggested in mammals except for the apparent capacity of rainbow trout to detect changes in MCFA levels. Changes in those hypothalamic pathways can be related to the control of food intake, since food intake was inhibited when FA metabolism was perturbed (using fatty acid synthase or acetyl-CoA carboxylase inhibitors) and changes in mRNA levels of specific neuropeptides such as neuropeptide Y and proopiomelancortin were also noticed. This response seems to be exclusive for the hypothalamus, since the other center controlling food intake (hindbrain) was unaffected by treatments. The results obtained in BB suggest that at least two of the components of a putative fatty acid-sensing system (based on fatty acid metabolism and binding to CD36) could be present. Therefore, the present study provides, for the first time in fish, evidence for a specific role for FA (MCFA and LCFA) as metabolic signals in hypothalamus and BB, where the detection of those FA can be associated with the control of food intake and hormone release.


2015 ◽  
Vol 53 ◽  
pp. 124-135 ◽  
Author(s):  
M. Librán-Pérez ◽  
C. Velasco ◽  
C. Otero-Rodiño ◽  
M.A. López-Patiño ◽  
J.M. Míguez ◽  
...  

Peptides ◽  
2011 ◽  
Vol 32 (2) ◽  
pp. 232-240 ◽  
Author(s):  
Ariel J. Aguilar ◽  
Marta Conde-Sieira ◽  
Marcos A. López-Patiño ◽  
Jesús M. Míguez ◽  
José L. Soengas

2015 ◽  
Vol 228 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Cristina Velasco ◽  
Marta Librán-Pérez ◽  
Cristina Otero-Rodiño ◽  
Marcos A López-Patiño ◽  
Jesús M Míguez ◽  
...  

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.


2016 ◽  
Vol 311 (4) ◽  
pp. R658-R668 ◽  
Author(s):  
Cristina Velasco ◽  
Marta Librán-Pérez ◽  
Cristina Otero-Rodiño ◽  
Marcos A. López-Patiño ◽  
Jesús M. Míguez ◽  
...  

We hypothesize that ceramides are involved in the regulation of food intake in fish. Therefore, we assessed in rainbow trout ( Oncorhynchus mykiss) the effects of intracerebroventricular treatment with C6:0 ceramide on food intake. In a second experiment, we assessed the effects in brain areas of ceramide treatment on neuropeptide expression, fatty acid-sensing systems, and cellular signaling pathways. Ceramide treatment induced a decrease in food intake, a response opposed to the orexigenic effect described in mammals, which can be related to enhanced mRNA abundance of cocaine and amphetamine-related transcript and proopiomelanocortin and decreased mRNA abundance of Agouti-related protein and neuropeptide Y. Fatty acid-sensing systems appear to be inactivated by ceramide treatment. The mRNA abundance of integrative sensors AMPK and sirtuin 1, and the phosphorylation status of cellular signaling pathways dependent on protein kinase B, AMPK, mammalian target of rapamycin (mTOR), and forkhead box protein O1 (FoxO1) are generally activated by ceramide treatment. However, there are differences between hypothalamus and hindbrain in the phosphorylation status of AMPK (decreased in hypothalamus and increased in hindbrain), mTOR (decreased in hypothalamus and increased in hindbrain), and FoxO1 (increased in hypothalamus and decreased in hindbrain) to ceramide treatment. The results suggest that ceramides are involved in the regulation of food intake in rainbow trout through mechanisms comparable to those characterized previously in mammals in some cases.


2015 ◽  
Vol 218 (16) ◽  
pp. 2610-2619 ◽  
Author(s):  
M. Libran-Perez ◽  
I. Geurden ◽  
K. Dias ◽  
G. Corraze ◽  
S. Panserat ◽  
...  

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