RESUMEN
Ghrelin, known to stimulate adipogenesis, displays an endogenous secretory rhythmicity closely related to meal patterns. Therefore, a chronic imposed feeding schedule might induce modified ghrelin levels and consequently adiposity. Growing Wistar rats were schedule-fed by imposing a particular fixed feeding schedule of 3 meals/day without caloric restriction compared with total daily control intake. After 14 days, their body composition was measured by DEXA and compared with ad libitum-fed controls and to rats daily intraperitoneal injection with ghrelin. Feeding patterns, circadian activity, and pulsatile acylated ghrelin variations were monitored. After 14 days, rats on the imposed feeding schedule displayed, despite an equal daily calorie intake, a slower growth rate compared with ad libitum-fed controls. Moreover, schedule-fed rats exhibiting a feeding pattern with intermittent fasting periods had a higher fat/lean ratio compared with ad libitum-fed controls. Interestingly, ghrelin-treated rats also showed an increase in fat mass, but the fat/lean ratio was not significantly increased compared with controls. In the schedule-fed rats, spontaneous activity and acylated ghrelin levels were increased and associated with the scheduled meals, indicating anticipatory effects. Our results suggest that scheduled feeding, associated with intermittent fasting periods, even without nutrient/calorie restriction on a daily basis, results in adipogenesis. This repartitioning effect is associated with increased endogenous acylated ghrelin levels. This schedule-fed model points out the delicate role of meal frequency in adipogenesis and provides an investigative tool to clarify any effects of endogenous ghrelin without the need for ghrelin administration.
Asunto(s)
Adipogénesis/fisiología , Ingestión de Alimentos/fisiología , Ghrelina/metabolismo , Absorciometría de Fotón , Acilación , Animales , Glucemia/metabolismo , Composición Corporal/fisiología , Peso Corporal/fisiología , Ritmo Circadiano/fisiología , Ghrelina/farmacocinética , Crecimiento/fisiología , Masculino , Actividad Motora/fisiología , Ratas , Ratas Wistar , Aumento de Peso/fisiologíaRESUMEN
The aim of this study was to investigate the influence of isoenergetic substitution between the three energy delivering macronutrients in pre-starter diets on performance and intermediary nutrient metabolism in broiler chickens. From hatch until 5 days of age, 600 chicks, collected during peak of hatch, were fed one of the three experimental pre-starter diets with isoenergetic (13 MJ metabolisable energy/kg) substitutions between fat (43 vs. 108 g/kg), protein (126 vs. 240 g/kg) and carbohydrates (391 vs. 510 g/kg). After 5 days, commercial grower and finisher diets were provided. Pre-starter composition influenced body weight until slaughter age, although not statistically verifiable. Broilers fed the low protein (LP) pre-starter had the lowest body weight in relation to chickens on the low carbohydrate or low fat pre-starter diet. After hatch, chicks on the LP pre-starter diet were able to use the residual yolk sac more rapidly to fulfil their protein requirement, which is reflected in small intestine and liver development. Also, plasma metabolite levels were influenced mostly by the LP pre-starter, indicating that the main focus for the requirements of newly hatched chicks should be on proteins. Furthermore, optimal nutrition during the first day's post-hatch should take into account the contribution of the yolk.
Asunto(s)
Alimentación Animal/análisis , Pollos/crecimiento & desarrollo , Dieta/veterinaria , Carbohidratos de la Dieta/farmacología , Grasas de la Dieta/farmacología , Proteínas en la Dieta/farmacología , Envejecimiento , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Pollos/metabolismo , Carbohidratos de la Dieta/análisis , Grasas de la Dieta/análisis , Proteínas en la Dieta/análisis , Ingestión de Energía , Metabolismo Energético , Intestino Delgado/anatomía & histología , Intestino Delgado/efectos de los fármacos , Hígado/anatomía & histología , Hígado/efectos de los fármacos , Tamaño de los Órganos , Aumento de Peso/efectos de los fármacosRESUMEN
Cholecystokinin (CCK) is known to have a short biological half-life. In order to prolong the half-life and create a new investigative tool, we previously PEGylated the peptide, yielding PEG-CCK(9), and demonstrated that it had a dose-dependent prolonged anorectic effect. The aim of this study was to investigate whether PEG-CCK(9) reduces food intake by inducing satiation or by abnormal physiological effects, such as pain, malaise, or nausea. An observational study was performed to examine the effects of different doses of PEG-CCK(9) (1, 2, 4, 8, or 16 microg kg(-1)) on feeding and other behaviors. The behavioral sequence associated with satiety (BSS), i.e. the orderly progression from eating, through grooming and activity, to resting, was analyzed. From the lowest dose tested (1 microg kg(-1)), PEG-CCK(9) caused a dose-dependent reduction in food intake due to a dose-related reduction in both the duration and frequency of eating and a dose-dependent increase in duration of rest. A dose-dependent acceleration in the temporal profile of the BSS was observed, while the normal structure of feeding behaviors was well preserved, except at the dose of 16 microg kg(-1) of PEG-CCK(9), at which a decrease in eating rate and grooming behavior was observed, together with the occurrence of a significant number of abdominal cramps. These findings suggest that the hypophagic response to PEG-CCK(9) is mainly induced by natural mechanisms of satiety, although abnormal physiological effects, such as abdominal cramps, might reinforce the food inhibitory effect, especially at high doses of PEG-CCK(9) (>8 microg kg(-1)).
Asunto(s)
Colecistoquinina/farmacología , Conducta Alimentaria/efectos de los fármacos , Respuesta de Saciedad/efectos de los fármacos , Animales , Colecistoquinina/administración & dosificación , Relación Dosis-Respuesta a Droga , Aseo Animal/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , Polietilenglicoles/química , Ratas , Ratas WistarRESUMEN
BACKGROUND AND PURPOSE: The physiological involvement of endogenous cholecystokinin (CCK) in the termination of feeding has been challenged by evidence of aversive effects of exogenous CCK8. We previously prolonged the anorectic effect of CCK by conjugation to polyethylene glycol (PEGylation) to produce PEG-CCK9. In this study, we investigated the ability of different doses of PEG-CCK9 to induce conditioned taste aversion (CTA) and satiety and identified the receptors involved in CTA induction. EXPERIMENTAL APPROACH: Induction of CTA, measured by the saccharin preference ratio determined in a two-bottle CTA procedure, and of satiety in adult male Wistar rats after intraperitoneal (i.p.) injection of different doses of PEG-CCK9 (1, 2, 4, 8, 16 or 32 microg kg(-1)) was compared. Devazepide (100 microg kg(-1)) and 2-NAP (3 mg kg(-1)), two selective CCK1-receptor antagonists, were co-administered i.p. with PEG-CCK9 (8 microg kg(-1)) and the CTA effects monitored. KEY RESULTS: PEG-CCK9 dose-dependently induced CTA, with a minimal effective dose of 8 microg kg(-1), whereas the minimal effective dose to induce satiety was 1 microg kg(-1). The CTA effects of PEG-CCK9 were completely abolished by i.p. administration of devazepide prior to PEG-CCK9 treatment and only partially abolished by administration of 2-NAP. CONCLUSIONS AND IMPLICATIONS: Although PEG-CCK9-induced satiety and PEG-CCK9-induced CTA both increased with dose, the conjugate was more potent in inducing satiety, suggesting that the anorexia could not be completely attributed to the aversiveness of the drug. As observed with induction of satiety, PEG-CCK9-induced CTA was mediated by CCK1-receptors.
Asunto(s)
Anorexia/inducido químicamente , Colecistoquinina/farmacología , Fragmentos de Péptidos/farmacología , Receptor de Colecistoquinina A/efectos de los fármacos , Respuesta de Saciedad/efectos de los fármacos , Animales , Ácido Aspártico/análogos & derivados , Ácido Aspártico/farmacología , Reacción de Prevención/efectos de los fármacos , Colecistoquinina/administración & dosificación , Colecistoquinina/química , Devazepida/farmacología , Relación Dosis-Respuesta a Droga , Inyecciones Intraperitoneales , Masculino , Naftalenosulfonatos/farmacología , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/química , Polietilenglicoles/química , Ratas , Ratas Wistar , Receptor de Colecistoquinina A/metabolismo , Sacarina , GustoRESUMEN
BACKGROUND AND PURPOSE: Acute intraperitoneal (i.p.) administration of cholecystokinin (CCK) is known to induce a significant, but short-lasting, reduction in food intake, followed by recovery within hours. Therefore, we had covalently coupled CCK to a 10 kDa polyethylene glycol and showed that this conjugate, PEG-CCK(9), produced a significantly longer anorectic effect than unmodified CCK(9). The present study assessed the dose-dependency of this response and the effect of two selective CCK(1) receptor antagonists, with different abilities to cross the blood-brain barrier (BBB), on PEG-CCK(9)-induced anorexia. EXPERIMENTAL APPROACH: Food intake was measured, for up to 23 h, after i.p. administration of different doses (2, 4, 8, 16 and 32 microg kg(-1)) of CCK(9) or PEG-CCK(9) in male Wistar rats. Devazepide (100 microg kg(-1)), which penetrates the BBB or 2-NAP (3 mg kg(-1)), which does not cross the BBB, were coadministered i.p. with PEG-CCK(9) (6 microg kg(-1)) and food intake was monitored. KEY RESULTS: In PEG-CCK(9)-treated rats, a clear dose-dependency was seen for both the duration and initial intensity of the anorexia whereas, for CCK(9), only the initial intensity was dose-dependent. Intraperitoneal administration of devazepide or 2-NAP, injected immediately prior to PEG-CCK(9), completely abolished the anorectic effect of PEG-CCK(9). CONCLUSIONS AND IMPLICATIONS: The duration of the anorexia for PEG-CCK(9) was dose-dependent, suggesting that PEGylation of CCK(9) increases its circulation time. Both devazepide and 2-NAP completely abolished the anorectic effect of i.p. PEG-CCK(9) indicating that its anorectic effect was solely due to stimulation of peripheral CCK(1) receptors.