Effects of omega-3 fatty acids on orexigenic and anorexigenic modulators at the onset of anorexia

In cancer anorexia, a decrease in food intake (FI) occurs concomitant with changes in orexigenic peptides such as neuropeptide Y (NPY) and anorexigenic peptides such as α-melanocyte-stimulating hormone (α-MSH) and anorexigenic neurotransmitter serotonin. ω-3 Fatty acid (ω-3FA) inhibits cytokine synthesis, and delays tumor appearance, tumor growth, and onset of anorexia in tumor-bearing rats. We hypothesize that, in cancer anorexia, ω-3FA is associated with quantitative reversal of hypothalamic NPY, α-MSH, and serotonin receptor (5-HT1B-receptor) enhancing FI. Fischer rats were divided into: MCA tumor bearing fed chow (TB-Chow) or ω-3FA diet (TB-ω-3FA) and controls: non-tumor bearing fed chow (NTB-Chow) or ω-3FA diet (NTB-ω-3FA). Rats were euthanized at anorexia and brains were removed for hypothalamic immunohistochemical study, using NPY, α-MSH, and 5-HT1B-receptor-specific antibodies and slides assessed by image analysis. Immunostaining specificity was controlled by omission of primary or secondary antibodies and pre-absorption test. At anorexia, FI decreased (P < 0.05) in TB-Chow but did not change in TB-ω-3FA rats. In TB-ω-3FA vs. TB-Chow, NPY immunoreactivity increased 38% in arcuate nucleus (ARC; P < 0.05), and 50% in magnocellular paraventricular nucleus (mPVN; P < 0.05). α-MSH decreased 64% in ARC and 29% in mPVN (P < 0.05). 5-HT1B-receptor immunoreactivity decreased 13% only in supraoptic nucleus (P < 0.05). No immunoreactivity was found in the control sections. ω-3FA modified hypothalamic peptides and 5-HT-1B-receptor immunoreactivity at anorexia, concomitant with an increase in FI, were probably mediated by ω-3FA inhibition of tumor-induced cytokines.