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Effect of feed restriction and supplemental dietary fat on gut peptide and hypothalamic neuropeptide mRNA concentrations in growing wethers

A. E. Relling^*,, J. L. Pate, C. K. Reynolds and S. C. Loerch

^* Ohio State University Interdisciplinary Nutrition Program (OSUN) , Department of Animal Sciences, The Ohio State University, Ohio Agric. Res. and Dev. Center, Wooster 44691-4096 , Department of Dairy and Animal Science, The Pennsylvania State University, University Park 16802 School of Agriculture, Policy and Development, University of Reading, Earley Gate, Reading RG6 6AR, United Kingdom

loerch.1{at}osu.edu

Abstract

The objectives of the present study were: 1) to evaluate the effect of supplemental fat and ME intake (MEI) on plasma concentrations of glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP), ghrelin and oxyntomodulin (OXM); and 2) to determine the association of these peptides with DMI and the hypothalamic concentration of messenger (m) RNA for the neuropeptides:neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC). Using a completely randomized block design with a 2 x 2 factorial arrangement of treatments, 32 pens with 2 wethers each were restricted-fed (2.45 Mcal•lamb^-1•d^-1) or offered feed ad libitum (n = 16) diets with or without 6% supplemental fat (n = 16) for a period of 30 d. Dry matter intake was measured daily. On d 8, 15, 22, and 29, BW was measured before feeding and 6 h after feeding blood samples were collected for plasma measurement of insulin, GLP-1, CCK, ghrelin, GIP, OXM, glucose and NEFA concentrations. On d 29, blood was collected 30 min before feeding for the same hormone and metabolite analyses. At the end of the experiment, wethers were slaughtered and the hypothalami were collected to measure concentration of NPY, AgRP, and POMC mRNA. Offering feed ad libitum (resulting in greater MEI) , increased plasma insulin and NEFA concentration (P = 0.02 and 0.02, respectively) and decreased hypothalamic mRNA expression of NPY and AgRP (P = 0.07 and 0.02, respectively) compared with the restricted-fed wethers. There was a trend for the addition of dietary fat to decrease DMI (P = 0.12). Addition of dietary fat decreased insulin and glucose concentration (P < 0.05 and 0.01, respectively) and tended to increase hypothalamic mRNA concentration for NPY and AgRP (P = 0.07 and 0.11, respectively). Plasma GLP-1 and CCK concentration increased in wethers offered feed ad libitum compared with those restricted-fed, but the response was greater when wethers were offered feed ad libitum and had supplemental fat in the diet (fat x intake interaction, P = 0.04). Pre-feeding plasma ghrelin concentration was higher in the restricted-fed wethers compared with those offered feed ad libitum, but the concentration was similar 6 h after feeding (Intake x Time interaction, P < 0.01). Supplemental dietary fat did not affect (P = 0.22) plasma ghrelin concentration. We conclude that insulin, ghrelin, CCK and GLP-1 may regulate DMI in sheep by regulating the hypothalamic gene expression of NPY, AgRP, and POMC.

Key Words: agouti-related peptide • gut peptides • insulin • intake • neuropeptide Y • sheep