Effect of gut peptides on hypothalamic mRNA concentration and dry matter intake in ruminants.

摘要

A series of six experiments was conducted to gain a better understanding of mechanisms involved in feed intake regulation by ruminants. Specifically, this dissertation investigated the effect of changes in concentrations of metabolites (i.e., glucose and non-esterified fatty acids (NEFA)), and hormones (i.e., insulin, glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), ghrelin, cholecystokinin (CCK) and oxyntomodulin (OXM)), on dry matter intake (DMI) and Hypothalamic mRNA concentration of neuropeptide Y (NPY), agouti-related peptide (AgRP) and proopiomelanocortin (POMC) in ruminants.;In Chapter 3, in vitro experiments were performed to determine the effect of metabolites (glucose and propionate), and the splanchnic hormones insulin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and polypeptide YY (PYY), on sheep Hypothalamic mRNA concentration for neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC). The incubation of sheep hypothalamus in glucose, propionate, insulin, CCK, GLP-1, or PYY did not affect the mRNA concentration for NPY, AgRP, or POMC compared with incubation of hypothalamus in the control media. Hypothalamus incubated in media containing glucose plus insulin did not result in changes in mRNA for NPY or AgRP, but increased POMC mRNA concentration compared with hypothalamus incubated in the control media. This implies that an interaction of factors, i.e. hormones and/or metabolites is needed to change the mRNA concentration of neuropeptides that regulate DMI.;In Chapter 4, the effect of feeding fat and restricting DMI on plasma concentrations of insulin, GLP-1, GIP, CCK, ghrelin and oxyntomodulin (OXM) and the hypothalamic concentration of the neuro-peptides NPY, AgRP and POMC in growing lambs were reported. Feeding wethers ad libitum increased plasma insulin, GIP and NEFA concentration and decreased hypothalamic mRNA expression of NPY and AgRP compared with feeding wethers at a restricted intake. The addition of dietary fat decreased DMI, insulin and glucose concentration and increased plasma GIP and hypothalamic mRNA concentration for NPY and AgRP. Plasma GLP-1 and CCK concentration increased for wethers fed ad libitum compared with those restricted-fed, but for those fed ad libitum, the response was greater when they had supplemental fat in the diet. Pre-feeding plasma ghrelin concentration was higher in the restricted compared with the ad libitum-fed wethers, but the concentration was similar after feeding.;In Chapters 5 and 6, the effects of infusion of physiological doses of GLP-1 and CCK on DMI are described. In Chapter 5, infusion of GLP-1, but not CCK, had effects on DMI and initial meal size similar to effects of feeding fat. However, in Chapter 6 the results of GLP-1 infusion do not support the results of Chapter 5. Based on these and other results from these studies, it is apparent that there are many other factors, independent of GLP-1, that regulate DMI. Moreover, it is likely that effects of feeding fat on DMI are due to additive effects of multiple hormones and metabolic signals, not solely to changes in plasma GLP-1 or CCK concentration.;Chapter 7 described the validation of an OXM assay for bovine plasma, and acute (hours) and chronic (1 week) effects of increased abomasal supply of protein (casein), carbohydrate (starch), or fat (soybean oil) to the small intestine on plasma concentrations of ghrelin and OXM on days 1 and 7 of infusion. Oil and casein infusion decreased prefeeding plasma ghrelin concentration on both days. The infusion of oil, starch or casein did not change plasma OXM concentration. The present data indicate that the decrease in plasma ghrelin concentration due to oil infusion could be associated with a decrease in DMI; however, the decrease in ghrelin concentration due to casein infusion was not associated with a decrease in DMI, and that plasma OXM concentration is not associated with DMI.;From the results in the current dissertation, it can be concluded that GLP-1 has a role in regulating DMI, but GLP-1 is not the sole factor that determines appetite. Results of these experiments suggest that the interaction among metabolic hormones and metabolites, and their combined effects, are more important for the regulation of DMI in ruminants than a single factor such as GLP1.