RESUMEN
The hippocampus and the medial prefrontal cortex (mPFC) are traditionally associated with regulating memory and executive function, respectively. The contribution of these brain regions to food intake control, however, is poorly understood. The present study identifies a novel neural pathway through which monosynaptic glutamatergic ventral hippocampal field CA1 (vCA1) to mPFC connectivity inhibits food-motivated behaviors through vCA1 glucagon-like peptide-1 receptor (GLP-1R). Results demonstrate that vCA1-targeted RNA interference-mediated GLP-1R knockdown increases motivated operant responding for palatable food. Chemogenetic disconnection of monosynaptic glutamatergic vCA1 to mPFC projections using designer receptors exclusively activated by designer drugs (DREADDs)-mediated synaptic silencing ablates the food intake and body weight reduction following vCA1 GLP-1R activation. Neuropharmacological experiments further reveal that vCA1 GLP-1R activation reduces food intake and inhibits impulsive operant responding for palatable food via downstream communication to mPFC NMDA receptors. Overall these findings identify a novel neural pathway regulating higher-order cognitive aspects of feeding behavior.
Asunto(s)
Ingestión de Alimentos/fisiología , Conducta Alimentaria/fisiología , Péptido 1 Similar al Glucagón/fisiología , Animales , Región CA1 Hipocampal/fisiología , Conducta Alimentaria/efectos de los fármacos , Alimentos , Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/genética , Receptor del Péptido 1 Similar al Glucagón/fisiología , Hipocampo/fisiología , Masculino , Motivación/fisiología , Vías Nerviosas/fisiología , Corteza Prefrontal/fisiopatología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/fisiologíaRESUMEN
Changes in metabolic state, such as those induced by fasting, have profound effects on reproduction. In rats, the time-course over which fasting inhibits luteinising hormone (LH) release is reduced to 48 h by the presence of oestradiol-17beta (E(2)). Hypothalamic kisspeptin plays a key role in mediating the actions of E(2) on gonadotrophin-releasing hormone (GnRH) neurones, and thereby promotes LH release. KiSS-1-expressing neurones are found in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Extensive evidence implicates the AVPV in GnRH release and the ARC in energy balance. The latter nucleus also contains neurones that express neuropeptide Y (NPY), an orexigenic peptide implicated in GnRH control. To elucidate the involvement of kisspeptin and/or NPY in hypothalamic responses to fasting, their expression was quantified by in situ hybridisation histochemistry in ovariectomised rats, with or without E(2) replacement, before and after 48 h of fasting. In the presence of E(2), but not in its absence, the fasting suppressed plasma LH. In the AVPV, the low level of KiSS-1 expression found in the absence of E(2) was unaffected by fasting. By contrast, the elevated level found in the presence of E(2) was suppressed by fasting. Independent of E(2), fasting had no effect on KiSS-1 expression in the ARC, but increased NPY expression at that site. The present study has identified the AVPV as a site at which KiSS-1 expression can be influenced by fasting. The results suggest that inhibition of KiSS-1 expression in the AVPV may be a significant factor in restraining the gonadotrophic axis in response to negative energy balance in the presence of oestrogen. The extent to which the concurrent rise in NPY expression in the ARC may contribute to the suppression of LH release by influencing AVPV kisspeptin neurones, directly or indirectly, or by actions independent of kisspeptin, remains to be established.
Asunto(s)
Núcleos Talámicos Anteriores/metabolismo , Núcleo Arqueado del Hipotálamo/metabolismo , Ayuno/fisiología , Neuropéptido Y/genética , Proteínas/genética , Animales , Peso Corporal/fisiología , Regulación hacia Abajo/genética , Ayuno/sangre , Ayuno/metabolismo , Femenino , Kisspeptinas , Hormona Luteinizante/sangre , Neuronas Aferentes/metabolismo , Neuropéptido Y/metabolismo , Proteínas/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas WistarRESUMEN
The present series of studies aimed to further our understanding of the role of melanin-concentrating hormone (MCH) neurones in the central regulation of luteinising hormone (LH) release in the female rat. LH release was stimulated when MCH was injected bilaterally into the rostral preoptic area (rPOA) or medial preoptic area (mPOA), but not when injected into the zona incerta (ZI), of oestrogen-primed ovariectomised rats. In rats that were steroid-primed to generate a surge-like release of LH, MCH administration into the ZI blocked this rise in LH release: no such effect occurred when MCH was injected into the rPOA or mPOA. In vitro, MCH stimulated gonadotrophin-releasing hormone (GnRH) release from hypothalamic explants. Double-label immunohistochemistry showed GnRH-immunoreactive neurones in the vicinity of and intermingled with immunoreactive MCH processes. MCH is the endogenous ligand of the MCH type 1 receptor (MCH1-R). Previously, we have shown a role for melanocortin-5 receptors (MC5-R) in the stimulatory action of MCH, so we next investigated the involvement of both MCH1-R and/or MC5-R in mediating the actions of MCH on GnRH and hence LH release. The stimulatory action of MCH in the rPOA was inhibited by administration of antagonists for either MCH1-R or MC5-R. However, in the mPOA, the action of MCH was blocked only by the MC5-R antagonist. LH release was stimulated by an agonist for MC5-R injected into the rPOA or mPOA; this was blocked by the MC5-R antagonist but not the MCH1-R antagonist. These results indicate that both MCH1-R and MC5-R are involved in the central control of LH release by MCH.
Asunto(s)
Hormonas Hipotalámicas/farmacología , Hormona Luteinizante/metabolismo , Melaninas/farmacología , Hormonas Hipofisarias/farmacología , Receptores de Corticotropina/fisiología , Receptores de Somatostatina/fisiología , Animales , Femenino , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Inmunohistoquímica , Ovariectomía , Ratas , Ratas Wistar , Receptores de MelanocortinaRESUMEN
Various studies implicate corticotropin-releasing hormone (CRH) as a mediator for the inhibitory effects of stress on reproduction. This study was designed to elucidate the underlying neuroanatomy. The retrograde tracer cholera toxin was picospritzed into the vicinity of the luteinizing hormone-releasing hormone (LHRH) perikarya. CRH neurones were examined for the tracer in the medial preoptic nucleus (MPO), bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN), central amygdaloid nucleus (CeM), parabrachial nucleus (PB) and additional locations. Retrograde label was not detected in CRH neurones at any of these sites; nevertheless, in the MPO and PB, abundant retrogradely-labelled perikarya intermingled with CRH neurones. In the BST, CeM and PVN, sites containing major CRH cell populations, retrogradely-labelled cells were scarce or absent; however, retrograde labelling was found in adjacent regions: lateral septum, medial amygdaloid nucleus and areas bordering the PVN. Double-label in situ hybridization for the mRNAs for LHRH and the CRH type-1 receptor (CRH-R1) identified the receptor transcript at sites rostral and lateral to the LHRH neurones (in the vertical and horizontal limbs of the diagonal band) but not in the LHRH neurones. Given the ability of oestrogen to potentiate stress-induced suppression of LH release, the identification of CRH neurones immunoreactive for oestrogen receptor (ER) alpha in the MPO and for ER beta in the caudal PVN may be significant. In this context, it is also noteworthy that CRH neurones within the MPO and PB which are, respectively, immunopositive and immunonegative for ER alpha, lie within the vicinity of retrogradely-labelled cells. The present findings suggest that the means by which CRH may mediate inhibitory effects of stressors on LH release do not involve direct CRH projections to LHRH neurones; the indirect means for such regulation, and the sites at which oestrogen may potentiate the inhibitory response, remain to be established.
Asunto(s)
Hormona Liberadora de Corticotropina/metabolismo , Estrógenos/fisiología , Hormona Luteinizante/metabolismo , Reproducción/fisiología , Estrés Fisiológico/fisiopatología , Animales , Núcleo Celular/metabolismo , Femenino , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/citología , Núcleo Hipotalámico Paraventricular/fisiología , Área Preóptica/citología , Área Preóptica/fisiología , ARN Mensajero/análisis , Ratas , Ratas Wistar , Receptores de Hormona Liberadora de Corticotropina/genética , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Receptores de Estrógenos/metabolismoRESUMEN
Two hundred sixteen crossbred (PIC line 26 x Camborough 15) pigs were used in three trials to determine optimal digestible lysine levels during early (EF = 50 to 95 kg) and late (LF = 90 to 110 kg) finishing periods. Pigs were self-fed in sex groups of two in all trials. The assay diets for EF and LF periods were 11 and 10% CP corn-soybean meal diets, respectively, supplemented with threonine, methionine, tryptophan, valine, and isoleucine. Corn-soybean meal positive-control diets were included in each trial (14.5% CP for EF and 13.5% CP for LF). This dietary CP regimen was shown to give the same performance and carcass quality as a 17% CP corn-soybean meal diet fed during both EF and LF. Plateau portions of the lysine response curves resulted in performance levels that were equal to or greater than those achieved with pigs fed the 14.5/13.5% CP positive-control diets. Early-finishing pigs responded (P < .05) to graded doses of digestible lysine (.41 to .71%) for daily weight gain, gain:feed, longissimus muscle area, 10th-rib fat depth, lean gain, and plasma urea N. Digestible lysine requirement estimates based on average plateau points were .58% for EF barrows and .64% for EF gilts. Late-finishing pigs responded (P < .05) to digestible lysine doses (.35 to .65%) for daily weight gain, gain:feed, lean gain, and plasma urea N. Digestible lysine requirement estimates based on average plateau points were .49% for LF barrows and .52% for LF gilts.
Asunto(s)
Envejecimiento/metabolismo , Alimentación Animal/normas , Lisina/metabolismo , Porcinos/crecimiento & desarrollo , Aminoácidos/análisis , Animales , Nitrógeno de la Urea Sanguínea , Composición Corporal/fisiología , Femenino , Alimentos Fortificados , Lisina/análisis , Masculino , Necesidades Nutricionales , Distribución Aleatoria , Caracteres Sexuales , Glycine max/química , Glycine max/normas , Porcinos/metabolismo , Aumento de Peso/fisiología , Zea mays/química , Zea mays/normasRESUMEN
Forty-eight crossbred (PIC line 26 x Camborough 15) pigs were used in two finishing trials to compare the ideal ratios of threonine (Thr), tryptophan (Trp), and sulfur amino acids (SAA) to lysine (Lys) determined for young pigs to a proposed ratio of these amino acids for finishing pigs. Trial 1 involved 20 barrows and 20 gilts that were self-fed in sex groups of two. Trial 2 was a Latin square design that used four barrows and four gilts that were individually fed in metabolism cages. Separate diets were used for the early (EF = 56 to 90 kg) and late (LF = 90 to 112 kg) finishing periods. Diets were formulated from a corn-soybean meal mixture and contained 11% CP and .55% digestible lysine for EF pigs and 10% CP and .50% digestible lysine for LF pigs. Negative-control diets in both the EF and LF periods were designed to be slightly deficient in lysine and to contain digestible Thr (65%), Trp (18%), and SAA (60%) at the ideal ratio to digestible Lys determined for 10- to 20-kg pigs. The experimental diet in both the EF and LF periods was formulated to contain digestible Thr (70%), Trp (20%), and SAA (65%) at the proposed ideal ratio to digestible Lys for finishing pigs. In Trial 1, increased ratios of Thr, Trp, and SAA improved gain:feed ratio, whole-body and carcass protein concentration, and whole-body and carcass protein accretion. In Trial 2, LF pigs responded to the increased ratios of Thr, Trp, and SAA with decreased urinary nitrogen excretion and increased N retention.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Aminoácidos Sulfúricos/normas , Dieta/veterinaria , Lisina/normas , Porcinos/crecimiento & desarrollo , Treonina/normas , Triptófano/normas , Aminoácidos Sulfúricos/análisis , Alimentación Animal/análisis , Alimentación Animal/normas , Animales , Nitrógeno de la Urea Sanguínea , Femenino , Lisina/análisis , Masculino , Distribución Aleatoria , Glycine max/química , Glycine max/normas , Treonina/análisis , Triptófano/análisis , Zea mays/química , Zea mays/normasRESUMEN
Three trials were conducted to evaluate high levels of Zn addition from various Zn sources on growth performance and plasma Zn responses of 8-kg pigs. Zinc supplements were added to 20% CP starting diets (125 mg of Zn/kg) containing antibiotics. Trial 1 was done to evaluate plasma Zn responses of pigs fed three different feed-grade Zn sources: ZnO where supplemental Zn levels were 0, 250, 500, 1,000, 3,000, and 5,000 mg/kg; ZnSO4 at 1,500 or 2,500 mg of Zn/kg; and a zinc-lysine complex (Zn-Lys) at 1,500 or 2,500 mg of Zn/kg. Plasma Zn concentration as a function of supplemental Zn intake was fitted to a broken-line for ZnO data and to simple linear models for ZnSO4 and Zn-Lys data. For ZnO, plasma Zn did not increase until concentrations > 1,000 mg Zn/kg were fed. Above this level, plasma Zn increased linearly (P < .01) for all three sources of Zn, although slopes of the ZnO and Zn-Lys response curves were 56% (P < .05) and 110%, respectively, of the ZnSO4 slopes. In Trial 2, five diets were fed: basal, 3,000 and 5,000 mg of Zn/kg from ZnO, and 3,000 and 5,000 mg of Zn/kg from ZnSO4. Daily gain and daily feed intake were increased (P < .05) by ZnO addition, regardless of level, whereas ZnSO4 addition increased these performance indices only at the 3,000 mg of Zn/kg level of supplementation. Plasma Zn responses to ZnSO4 addition were almost double those of ZnO addition.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Porcinos/crecimiento & desarrollo , Zinc/administración & dosificación , Alimentación Animal , Animales , Femenino , Alimentos Fortificados , Masculino , Sulfatos/administración & dosificación , Porcinos/sangre , Aumento de Peso/efectos de los fármacos , Zinc/sangre , Compuestos de Zinc/administración & dosificación , Óxido de Zinc/administración & dosificación , Sulfato de ZincRESUMEN
Oat flour, the by-product resulting from commercial production of oat bran, was analyzed to contain 7.7% moisture, 11% CP, 6% crude fat, 8.8% NDF, 1.56% ash (.10% Ca, .23% P), 4,265 kcal/kg GE, .41% lysine, .36% threonine, .17% tryptophan, .21% methionine and .34% cystine. Chick bioassays revealed that lysine and threonine were the first- and second-limiting amino acids in oat flour. Slope-ratio protein quality assessment indicated that the protein quality of oat flour was similar to that of dehulled soybean meal. True ME (corrected for N retention, i.e., TMEn) of oat flour for adult cockerels was 3,726 kcal/kg. A P bioavailability assay with chicks indicated that the P in oat flour was 59.7% bioavailable relative to a KH2PO4 standard. Oat bran was analyzed to contain 9.7% moisture, 15% CP, 6.2% crude fat, 19.2% NDF, 2.33% ash (.12% Ca, .41% P), 4,316 kcal/kg GE, .59% lysine, .47% threonine, .18% tryptophan, .24% methionine and .44% cystine. Protein quality assessment in chicks indicated that the protein quality of oat bran was similar to that of dehulled soybean meal. True MEn of oat bran was found to be 3,449 kcal/kg. Of the .41% total phosphorus in oat bran, 42.2% was bioavailable, relative to the KH2PO4 standard.