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. 2015 Oct 15;309(8):E759-66.
doi: 10.1152/ajpendo.00346.2015. Epub 2015 Sep 1.

Peptide YY signaling in the lateral parabrachial nucleus increases food intake through the Y1 receptor

Amber L Alhadeff  1 , Danielle Golub  2 , Matthew R Hayes  3 , Harvey J Grill  2
Affiliations

Peptide YY signaling in the lateral parabrachial nucleus increases food intake through the Y1 receptor

Amber L Alhadeff et al. Am J Physiol Endocrinol Metab. .

Abstract

Although central PYY delivery potently increases food intake, the sites of action and mechanisms mediating these hyperphagic effects are not fully understood. The present studies investigate the contribution of lateral parabrachial nucleus (lPBN) PYY-Y receptor signaling to food intake control, as lPBN neurons express Y receptors and receive PYY fibers and are known to integrate circulating and visceral sensory signals to regulate energy balance. Immunohistochemical results identified a subpopulation of gigantocellular reticular nucleus PYY-producing neurons that project monosynaptically to the lPBN, providing an endogenous source of PYY to the lPBN. lPBN microinjection of PYY-(1-36) or PYY-(3-36) markedly increased food intake by increasing meal size. To determine which receptors mediate these behavioral results, we first performed quantitative real-time PCR to examine the relative levels of Y receptor expression in lPBN tissue. Gene expression analyses revealed that, while Y1, Y2, and Y5 receptors are each expressed in lPBN tissue, Y1 receptor mRNA is expressed at fivefold higher levels than the others. Furthermore, behavioral/pharmacological results demonstrated that the hyperphagic effects of PYY-(3-36) were eliminated by lPBN pretreatment with a selective Y1 receptor antagonist. Together, these results highlight the lPBN as a novel site of action for the intake-stimulatory effects of central PYY-Y1 receptor signaling.

Keywords: Y1 receptor; food intake; gigantocellular reticular nucleus; obesity; parabrachial nucleus; peptide YY.

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Figures

Fig. 1.
Fig. 1.
A: representative image of lateral parabrachial nucleus (lPBN) injection site (black arrow). B: diagram of injection sites in a cohort of rats in this study; numbers represent position (mm) relative to bregma; • represents hits; x represents misses.
Fig. 2.
Fig. 2.
A: omission of peptide YY (PYY) primary antibody (negative control) resulted in no PYY fiber immunofluorescence in the lPBN. B: PYY immunohistochemistry confirmed the presence of PYY fibers (white arrow) in the lPBN. C–E: representative ×20 magnification image of a Gi section: (C) green immunofluorescence represents PYY, (D) red immunofluorescence represents lPBN-injected Fluorogold(FG), (E) merged image shows colocalization of FG and PYY (white arrow). F: representative image of lPBN FG injection.
Fig. 3.
Fig. 3.
Intra-lPBN PYY-(1–36) microinjection (A) significantly increased cumulative chow intake but (B) had no effect on 24-h change in body weight. Likewise, intra-lPBN PYY-(3–36) microinjection (C) significantly increased cumulative chow intake but (D) had no effect on 24-h change in body weight (means ± SE; *P < 0.05, **P < 0.01).
Fig. 4.
Fig. 4.
Intra-lPBN PYY-(1–36) microinjection (A) significantly increased meal size and (B) had little effect on meal number (means ± SE; *+P < 0.10, *P < 0.05).
Fig. 5.
Fig. 5.
Intra-lPBN PYY-(3–36) microinjection (A) significantly increased meal size and (B) had no effect on meal number (means ± SE; +P < 0.10, *P < 0.05, **P < 0.01).
Fig. 6.
Fig. 6.
A: qPCR in lPBN tissue revealed that Y1 receptor (Y1R) mRNA was expressed ∼5 times higher than Y2R and Y5R mRNA. B: lPBN pretreatment with the selective Y1R antagonist LY-1229U91 attenuated the orexigenic effects of lPBN PYY-(3–36). Within a time bin, bars with different letters are significantly different from each other (means ± SE; P < 0.05).
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