Interplay Between Galanin and Leptin in the Hypothalamic Control of Feeding via Corticotropin-Releasing Hormone and Neuropeptide Y

• Published in: Diabetes (New York, N.Y.) Vol. 50; no. 12; pp. 2666 - 2672
• Main Authors: BERGONZELLI, Gabriela E, PRALONG, Francois P, GLAUSER, Micheline, CAVADAS, Claudia, GROUZMANN, Eric, GAILLARD, Rolf C
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.12.2001
• Subjects: Animals; Axons - ultrastructure; Biological and medical sciences; Blotting, Northern; Cells, Cultured; Corticotropin-Releasing Hormone - genetics; Corticotropin-Releasing Hormone - metabolism; Corticotropin-Releasing Hormone - physiology; Drug Interactions; Eating - physiology; Embryo, Mammalian; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Galanin - administration & dosage; Galanin - pharmacology; Gene Expression - drug effects; Health aspects; Hypothalamus - drug effects; Hypothalamus - physiology; Immunohistochemistry; Leptin; Leptin - administration & dosage; Leptin - pharmacology; Microtubule-Associated Proteins - analysis; Neurites - ultrastructure; Neurons; Neurons - drug effects; Neurons - physiology; Neurons - ultrastructure; Neuropeptide Y; Neuropeptide Y - genetics; Neuropeptide Y - metabolism; Neuropeptide Y - physiology; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Neuropeptide Y; Feeding behavior; Galanin; Leptin; Central nervous system; Corticotropin releasing factor; Hypothalamus; Hormone releasing factor; Brain (vertebrata)
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.50.12.2666

Interplay Between Galanin and Leptin in the Hypothalamic Control of Feeding via Corticotropin-Releasing Hormone and Neuropeptide Y Gabriela E. Bergonzelli 1 , François P. Pralong 1 , Micheline Glauser 1 , Claudia Cavadas 2 3 , Eric Grouzmann 2 and Rolf C. Gaillard 1 1 Division of Endocrinology, University Hospital, Lausanne, Switzerland 2 Division of Hypertension, University Hospital, Lausanne, Switzerland 3 Laboratory of Pharmacology, Faculty of Pharmacy, Coimbra, Portugal Abstract Over long periods, feeding and metabolism are tightly regulated at the central level. The total amount of nutrients ingested is thought to result from a delicate balance between orexigenic and anorexigenic factors expressed and secreted by specialized hypothalamic neuronal populations. We have developed a system of perifused hypothalamic neurons to characterize the relationships existing between the orexigenic peptide galanin and two other physiological modulators of feeding: neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH). We demonstrated that galanin stimulates CRH and NPY secretion from hypothalamic neurons in a dose-dependent manner. Exposure to leptin for 24 h before galanin stimulation decreased NPY secretion by 30%, leaving the responsiveness of CRH neurons intact. These results suggest that CRH and NPY neurons participate to the intrahypothalamic signaling pathway of galanin, an observation that can explain the lower potency of galanin to stimulate food intake in vivo compared with NPY. The differential effects exerted by leptin on CRH and NPY suggest that there exists a subset of NPY neurons that are exquisitely sensitive to marked variations in leptin levels, and that the CRH neurons are less responsive to increases in leptin concentrations. Footnotes Address correspondence and reprint requests to François Pralong, Division of Endocrinology, CHUV BH-19-707, CH-1011 Lausanne, Switzerland. E-mail: francois.pralong{at}chuv.hospvd.ch . G.E.B. is currently affiliated with the Nutrition Department, Nestle Research Center, Lausanne, Switzerland. G.E.B. and F.P.P. contributed equally to this work. Received for publication 4 July 2001 and accepted in revised form 18 September 2001. araC, cytosine β- d -arabinofuranoside; AUC, area under the secretory curve; CRH, corticotropin-releasing hormone; GDH, glyceraldehyde phosphate dehydrogenase; GFAP, glial fibrillary acid protein; IRMA, immunoradiometric assay; MAP2, mitogen-activated protein 2; MCH, melanin-concentrating hormone; NPY, neuropeptide Y; POMC, pro-opio-melanocortin; PVN, paraventricular nucleus; RT-PCR, reverse transcriptase–polymerase chain reaction.