TY - JOUR
T1 - Pancreatic polypeptide controls energy homeostasis via Npy6r signaling in the suprachiasmatic nucleus in mice
AU - Yulyaningsih, Ernie
AU - Loh, Kim
AU - Lin, Shu
AU - Lau, Jackie
AU - Zhang, Lei
AU - Shi, Yanchuan
AU - Berning, Britt A.
AU - Enriquez, Ronaldo
AU - Driessler, Frank
AU - Macia, Laurence
AU - Khor, Ee Cheng
AU - Qi, Yue
AU - Baldock, Paul
AU - Sainsbury, Amanda
AU - Herzog, Herbert
N1 - Funding Information:
This work was supported by the National Health and Medical Research Council (NHMRC) of Australia in the form of a Postgraduate Scholarship to E.Y., a Fellowship to H.H., a Senior Research Fellowship to A.S., and project grant #427661 to H.H. and A.S. We thank Dr. Hal Gainer from the National Institute of Neurological Disorders and Stroke for his gifts of antibodies. We are grateful to Dr Robert Dallmann, Nguyen Dinh Nguyen, and Andrea Abdipranoto for their helpful discussions. We thank Felicity Forsyth for secretarial assistance.
PY - 2014/1/7
Y1 - 2014/1/7
N2 - Y-receptors control energy homeostasis, but the role of Npy6 receptors (Npy6r) is largely unknown. Young Npy6r-deficient (Npy6r-/-) mice have reduced body weight, lean mass, and adiposity, while older and high-fat-fed Npy6r-/- mice have low lean mass with increased adiposity. Npy6r-/- mice showed reduced hypothalamic growth hormone releasing hormone (Ghrh) expression and serum insulin-like growth factor-1 (IGF-1) levels relative to WT. This is likely due to impaired vasoactive intestinal peptide (VIP) signaling in the suprachiasmatic nucleus (SCN), where we found Npy6r coexpressed in VIP neurons. Peripheral administration of pancreatic polypeptide (PP) increased Fos expression in the SCN, increased energy expenditure, and reduced food intake in WT, but not Npy6r-/-, mice. Moreover, intraperitoneal (i.p.) PP injection increased hypothalamic Ghrh mRNA expression and serum IGF-1 levels in WT, but not Npy6r-/-, mice, an effect blocked by intracerebroventricular (i.c.v.) Vasoactive Intestinal Peptide (VPAC) receptors antagonism. Thus, PP-initiated signaling through Npy6r in VIP neurons regulates the growth hormone axis and body composition.
AB - Y-receptors control energy homeostasis, but the role of Npy6 receptors (Npy6r) is largely unknown. Young Npy6r-deficient (Npy6r-/-) mice have reduced body weight, lean mass, and adiposity, while older and high-fat-fed Npy6r-/- mice have low lean mass with increased adiposity. Npy6r-/- mice showed reduced hypothalamic growth hormone releasing hormone (Ghrh) expression and serum insulin-like growth factor-1 (IGF-1) levels relative to WT. This is likely due to impaired vasoactive intestinal peptide (VIP) signaling in the suprachiasmatic nucleus (SCN), where we found Npy6r coexpressed in VIP neurons. Peripheral administration of pancreatic polypeptide (PP) increased Fos expression in the SCN, increased energy expenditure, and reduced food intake in WT, but not Npy6r-/-, mice. Moreover, intraperitoneal (i.p.) PP injection increased hypothalamic Ghrh mRNA expression and serum IGF-1 levels in WT, but not Npy6r-/-, mice, an effect blocked by intracerebroventricular (i.c.v.) Vasoactive Intestinal Peptide (VPAC) receptors antagonism. Thus, PP-initiated signaling through Npy6r in VIP neurons regulates the growth hormone axis and body composition.
UR - http://www.scopus.com/inward/record.url?scp=84891879915&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2013.11.019
DO - 10.1016/j.cmet.2013.11.019
M3 - Article
C2 - 24411939
AN - SCOPUS:84891879915
SN - 1550-4131
VL - 19
SP - 58
EP - 72
JO - Cell Metabolism
JF - Cell Metabolism
IS - 1
ER -