Abstract
We hypothesize that a decrease in circulating levels of fatty acid (FA) in rainbow trout Oncorhynchus mykiss would result in the inhibition of putative hypothalamic FA sensing systems with concomitant changes in the expression of orexigenic and anorexigenic factors ultimately leading to a stimulation of food intake. To assess this hypothesis, we lowered circulating FA levels treating fish with SDZ WAG 994 (SDZ), a selective A1 adenosine receptor agonist that inhibits lipolysis. In additional groups, we also evaluated if the presence of intralipid was able to counteract changes induced by SDZ treatment, and the possible involvement of the hypothalamus-pituitary-interrenal (HPI) axis by treating fish with SDZ in the presence of metyrapone, which decreases cortisol synthesis in fish. The decrease in circulating levels of FA in rainbow trout induced a clear increase in food intake that was associated with the decrease of the anorexigenic potential in hypothalamus (decreased POMC-A1 and CART mRNA abundance), and with changes in several parameters related to putative FA-sensing mechanisms in hypothalamus. Intralipid treatment counteracted these changes. SDZ treatment also induced increased cortisol levels and the activation of different components of the HPI axis whereas these changes disappeared in the presence of intralipid or metyrapone. These results suggest that the HPI axis is involved in a counter-regulatory response in rainbow trout to restore FA levels in plasma.
Highlights
Specialized neurons within mammalian hypothalamus have been suggested to detect increases in plasma levels of long-chain fatty acid (LCFA), but not short-chain (SCFA) or medium-chain (MCFA) FA through several mechanisms [1,2,3], such as i) FA metabolism through inhibition of carnitine palmitoyltransferase 1 (CPT-1) to import FA-CoA into the mitochondria for oxidation; ii) binding to FA translocase (FAT/CD36), and further modulation of transcription factors like peroxisome proliferator-activated receptor type a (PPARa), and sterol regulatory element-binding protein type 1c (SREBP1c); iii) activation of protein kinase C-h; and iv) mitochondrial production of reactive oxygen species (ROS) by electron leakage resulting in an inhibition of ATP-dependent inward rectifier potassium channel (KATP) activity
FA (Fig. 2A) and triglyceride (Fig. 2B) levels decreased after SDZ treatment compared with all other groups
Glucose levels increased after treatment with SDZ +M compared with control and SDZ groups (Fig. 2D)
Summary
Specialized neurons within mammalian hypothalamus have been suggested to detect increases in plasma levels of long-chain fatty acid (LCFA), but not short-chain (SCFA) or medium-chain (MCFA) FA through several mechanisms [1,2,3], such as i) FA metabolism through inhibition of carnitine palmitoyltransferase 1 (CPT-1) to import FA-CoA into the mitochondria for oxidation; ii) binding to FA translocase (FAT/CD36), and further modulation of transcription factors like peroxisome proliferator-activated receptor type a (PPARa), and sterol regulatory element-binding protein type 1c (SREBP1c); iii) activation of protein kinase C-h; and iv) mitochondrial production of reactive oxygen species (ROS) by electron leakage resulting in an inhibition of ATP-dependent inward rectifier potassium channel (KATP) activity Changes in these systems have been associated [4] with the modulation of hypothalamic homeobox domain transcription factor (BSX), forkhead box 01 (Fox01), and phosphorylated cAMP responseelement binding protein (pCREB). In the hypothalamus of another fish species, the orange-spotted grouper (Epinephelus coioides), the involvement of FA metabolism and mitochondrial activity in the orexigenic effects of NPY has been suggested [17]
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