The long-chain fatty acid receptors FFA1 and FFA4 are involved in food intake regulation in fish brain

Abstract

We 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 acid (LCFA) like oleate. Therefore, in a first experiment we demonstrated that intracerebroventricular (ICV) treatment of rainbow trout with FFA1 and FFA4 agonists elicited an anorectic response 2, 6, and 24h after treatment. In a second experiment, the same ICV treatment resulted after 2h 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 to 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 2h of ICV treatment with oleate (the endogenous ligand of both FFARs) alone or in the presence of FFA1 and FFA4 antagonist. Most effects of oleate disappeared in the presence of FFA1 and FFA4 antagonist. The evidence obtained support the involvement of FFA1 and FFA4 in fatty acid sensing in fish brain, and thus being involved in food intake regulation through mechanisms not exactly comparable (differential response of neuropeptides and cellular signalling) to those known in mammals.