Central injection of oxytocin reduces food intake and affects hypothalamic and adipose tissue gene expression in chickens.

Oxytocin (OT) is a well-characterized neurotransmitter that participates in a wide range of physiological processes including the inhibition of food intake. The avian ortholog, mesotocin (MT), differs from OT by a single amino acid. Little is known regarding the function of OT in regulating energy balance in birds; thus, this study was designed to determine the effects of central OT injection on food intake and adipose tissue physiology in chicks. At 4-d post-hatch, broiler chicks were fasted for 3 h and injected intracerebroventricularly with 0 (vehicle), 0.63, 2.5, 5.0, or 10 nmol OT. Oxytocin decreased food and water intake during the entire 180-min observation period. The reduction in water intake was likely not prandial because chicks that were food restricted after OT injection also drank less. There was increased c-Fos immunoreactivity in several appetite-associated hypothalamic nuclei in OT-injected chicks at 1 h, including the arcuate (ARC), dorsomedial nucleus (DMN), lateral hypothalamus (LH), paraventricular nucleus (PVN), and ventromedial hypothalamus (VMH). OT treatment was associated with reduced hypothalamic corticotropin-releasing factor (CRF) mRNA and increased cloacal temperature at 1 h post-injection. We then investigated appetite- and adipose tissue-associated effects of OT in chicks from lines that have undergone long-term selection for either low (LWS) or high (HWS) juvenile body weight. Central injection of OT decreased food intake in both lines with the magnitude of response greater in the HWS than LWS chicks. Adipose tissue abundance of fatty acid-binding protein 4, monoglyceride lipase (MGLL), MT, and perilipin-1 mRNA was greater in LWS than HWS chicks. Lipoprotein lipase, MGLL, and MT mRNAs increased in response to OT injection in LWS but not HWS chicks. In conclusion, central injection of OT induced anorexia, reduced water intake, increased body temperature, and was associated with activation of the ARC, DMN, LH, PVN, and VMH in the hypothalamus. The effects on appetite and body temperature may involve CRF signaling in the hypothalamus and lipolysis in the adipose tissue, respectively. There were differences in the appetite, and adipose tissue response to OT in body weight-selected lines of chicks supports that MT plays a role in energy balance regulation in chickens.

Differential gene expression pattern in hypothalamus of chickens during fasting-induced metabolic reprogramming: functions of glucose and lipid metabolism in the feed intake of chickens.

Fasting-induced hypothalamic metabolic reprogramming is involved in regulating energy homeostasis and appetite in mammals, but this phenomenon remains unclear in poultry. In this study, the expression patterns of a panel of genes related to neuropeptides, glucose, and lipid metabolism enzymes in the hypothalamus of chickens during fasting and refeeding were characterized by microarray analysis and quantitative PCR. Results showed that 48 h of fasting upregulated (P < 0.05) the mRNA expressions of orexigenic neuropeptide Y and agouti-related protein but downregulated (P < 0.05) that of anorexigenic neuropeptide pro-opiomelanocortin; growth hormone-releasing hormone; islet amyloid polypeptide; thyroid-stimulating hormone, ß; and glycoprotein hormones, α polypeptide. After 48 h of fasting, the mRNA expression of fatty acid ß-oxidation [peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1A, and forkhead box O1], energy sensor protein [sirtuin 1 (SIRT1) and forkhead box O1], and glycolysis inhibitor (pyruvate dehydrogenase kinase, isozyme 4) were enhanced, but that of fatty acid synthesis and transport associated genes (acetyl-CoA carboxylase α, fatty acid synthase, apolipoprotein A-I, endothelial lipase, and fatty acid binding protein 7) were suppressed. Liver and muscle also demonstrated similar expression patterns of genes related to glucose and lipid metabolism with hypothalamus, except for that of acetyl-CoA carboxylase α, acyl-CoA synthetase long-chain family member 4, and apolipoprotein A-I. The results of intracerebroventricular (ICV) injection experiments confirmed that α-lipoic acid (ALA, pyruvate dehydrogenase kinase, isozyme 4 inhibitor, 0.10 µmol) and NADH (SIRT1 inhibitor, 0.80 µmol) significantly suppressed the appetite of chickens, whereas 2-deoxy-d-glucose (glycolytic inhibitor, 0.12 to 1.20 µmol) and NAD(+) (SIRT1 activator, 0.08 to 0.80 µmol) increased feed intake in chickens. The orexigenic effect of NAD(+) was also blocked by cotreatment with NADH. However, ICV injection of either GW7647 (PPARα agonist) or GW6471 (PPARα antagonist) showed no effects on feed intake. Results suggested that hypothalamic glycolysis (inhibited by ALA and promoted by 2-deoxy-d-glucose) and SIRT1 (inhibited by NADH and promoted by NAD(+)), not PPARα, were probably involved in feed intake regulation in chickens.

Central injection of exogenous IL-1ß in the control activities of hypothalamic-pituitary-gonadal axis in anestrous ewes.

This study was performed to determine the effect of intracerebroventricular (icv) injection of interleukin (IL)-1ß on the gene expression, translation and release of gonadotropin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) gene expression in the hypothalamus of anestrous ewes. In the anterior pituitary gland (AP), the expression of genes encoding: GnRHR, ß subunits of luteinizing hormone (LH) and folliculotropic hormone (FSH) was determined as well as the effect of IL-1ß on pituitary gonadotropins release. The relative mRNA level was determined by real-time PCR, GnRH concentration in the cerebrospinal fluid (CSF) was assayed by ELISA and the plasma concentration of LH and FSH were determined by radioimmunoassay. Our results showed that icv injection of IL-1ß (10 or 50 µg/animal) decreased the GnRH mRNA level in the pre-optic area (POA) (35% and 40% respectively; p ≤ 0.01) and median eminence (ME) (75% and 70% respectively; p ≤ 0.01) and GnRHR gene expression in ME (55% and 50% respectively; p ≤ 0.01). A significant decrease in GnRHR mRNA level in the AP in the group treated with the 50 µg (60%; p ≤ 0.01) but not with the 10 µg dose was observed. The centrally administrated IL-1ß lowered also GnRH concentration in the CSF (60%; p ≤ 0.01) and reduced the intensity of GnRH translation in the POA (p ≤ 0.01). It was not found any effect of icv IL-1ß injection upon the release of LH and FSH. However, the central injection of IL-1ß strongly decreased the LHß mRNA level (41% and 50%; p ≤ 0.01; respectively) and FSHß mRNA in the case of the 50 µg dose (49%; p ≤ 0.01) in the pituitary of anestrous ewes. These results demonstrate that the central IL-1ß is an important modulator of the GnRH biosynthesis and release during immune/inflammatory challenge.

Intracerebroventricular melanin-concentrating hormone stimulates food intake in sheep.

Melanin-concentrating hormone (MCH) stimulates feeding when injected intracerebroventricularly (ICV) in rats. At present it is not clear whether the function of MCH is similar in ruminants, which are species with a continuous delivery of nutrients. Therefore the current investigation sought to determine the role of MCH in sheep. In the first experiment, six, castrate male sheep were satiated and received one of four treatments [saline, 0.1, or 1.0 nmol/kg MCH, and NPY (0.1 nmol/kg)] injected ICV over 30s, then infused ICV for 6 h ( approximately 500 microl/h). Food intake was measured for 2 h before and at 2, 4, 6, 8, 12 and 24 h. In this experiment, feed intake was increased (P

Brain interleukin-1 is involved in blood interleukin-6 response to immobilization stress in rats.

Interleukin (IL)-6, a cytokine for host defense responses to infection and inflammation, is known to be induced by non-invasive physical or psychological stress, too. To test possible involvement of brain IL-1 in the stress-induced IL-6 production, IL-1 mRNA expression in the hypothalamus, in parallel with blood IL-6 level, was examined in rats subjected to restriction of their movement (immobilization stress). When rats were immobilized, the hypothalamic IL-1 beta mRNA level was increased in 1 hr, followed by progressive rises in the serum IL-6 level. The immobilization-induced rise in serum IL-6 was mimicked by intracerebroventricular (icv) administration of IL-1 beta under normal conditions, whereas it was attenuated by icv injection of an IL-1 receptor antagonist. These results indicate that IL-1 in the hypothalamus plays a pivotal mediating role in the stress-induced peripheral IL-6 production.

Serum prolactin and growth hormone responses to naloxone and intracerebral ventricle morphine administration in heifers.

These studies examined responses of serum prolactin (PRL) and growth hormone (GH) to opioid agonist and antagonist administration in heifers. To minimize nonspecific and behavioral effects and to facilitate future studies with specific opioid receptor agonists, a cannula was placed within the third cerebral ventricle of the brain of 4- to 10-mo-old heifers to directly access hypothalamic regions involved in the regulation of PRL and GH secretion. Increasing doses of morphine (M) from 2 to 1,500 micrograms injected into the third cerebral ventricle increased (P less than .001) serum PRL concentrations in a dose-related manner. Growth hormone responses were variable, resulting in elevated (P less than .05) serum concentrations following morphine, but no dose-related effects were apparent. Both PRL and GH responses to 700 micrograms M were absent when an intracerebral ventricle injection of an equimolar dose of naloxone, an opioid receptor antagonist, was administered prior to M. In a replicated 4 x 4 latin square, the effects of intravenous naloxone on PRL and GH responses was tested in young (86 +/- 11 d) and older (234 +/- 6 d) heifers. Naloxone at doses of 1, 2 and 4 mg/kg reduced (P less than .05) serum concentrations of PRL for 45 to 60 min. Mean concentrations of GH tended to be higher (P less than .07) in older heifers All doses of naloxone decreased (P less than .05) serum GH concentrations in older heifers but proved ineffective in younger heifers. There were no differences between doses of naloxone on either PRL or GH. These data suggest that endogenous opioids are involved in the regulation of PRL and GH secretion in heifers.