Takaoki Saneyasu

Central administration of insulin suppresses food intake in chicks

Although the orexigenic action of peptide hormones such as ghrelin and growth hormone releasing peptide is different between chickens and mammals, the anorexigenic action of peptide hormones is similar in both species. For example, central administration of peptide hormones such as leptin, cholecystokinin or glucagon has been shown to suppress food intake behavior in chickens and mammals. Central administration of insulin suppresses food intake in mammals. However, the anorexigenic action of insulin in chickens has not yet been identified. In the present study, we investigated the effects of central administration of insulin on food intake in chicks. Intracerebroventricular administration of insulin in chicks significantly suppressed food intake. Central administration of insulin significantly upregulated mRNA levels of proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART) and corticotropin-releasing factor (CRF), but did not influence mRNA levels of neuropeptide Y and agouti-related protein in the hypothalamus. These results suggest that alpha-melanocyte stimulating hormone (alpha-MSH, an anorexigenic peptide from the post-translational cleavage of POMC), CART and CRF are involved in the anorexigenic action of insulin in chicks. Furthermore, central administration of alpha-MSH or CART significantly suppressed food intake. In addition, alpha-MSH significantly upregulated CRF mRNA expression, suggesting that the anorexigenic action of alpha-MSH is mediated by CRF. Our findings demonstrate that insulin functions in chicks as an appetite-suppressive peptide in the central nervous system and suggest that this anorexigenic action is mediated by CART, alpha-MSH and CRF.

Neuropeptide Y effect on food intake in broiler and layer chicks.

Broiler chicks eat more food than layer chicks. In this study, we examined the involvement of orexigenic peptide neuropeptide Y (NPY) in the difference in food intake between broiler and layer chicks (Gallus gallus). First, we compared the hypothalamic mRNA levels of NPY and its receptors (Y1 and Y5 receptors) between these strains at 1, 2, 4, and 8 days of age. Daily food intake was significantly higher in broiler chicks than layer chicks after 2 days of age. However, the hypothalamic NPY mRNA level was significantly lower in broiler chicks than layer chicks except at 8 days of age. In addition, the mRNA levels of NPY receptors were also significantly lower in broiler chicks than layer chicks at 2 and 4 days of age (Y1 receptor) or 2 days of age (Y5 receptor). These results suggest that the differences in the expressions of hypothalamic NPY and its receptors do not cause the increase in food intake in broiler chicks. To compare the orexigenic effect of NPY between broiler and layer chicks, we next examined the effects of central administration of NPY on food intake in these strains. In both strains, central administration of NPY significantly increased food intake at 2, 4 and 8 days of age. All our findings demonstrated that the increase in food intake in broiler chicks is not accompanied with the over-expression of NPY or its receptor.

Central administration of neuromedin U suppresses food intake in chicks

The appetite-suppressive action of brain-gut peptides is similar in both chickens and mammals. In mammals, the brain-gut peptide neuromedin U (NMU) suppresses food intake via hypothalamic neuropeptides, corticotropin-releasing factor (CRF), oxytocin, and arginine-vasopressin. In chickens, central administration of CRF, oxytocin, or arginine-vasotocin (AVT, a nonmammalian equivalent of arginine-vasopressin) suppresses food intake. However, the anorexigenic action of NMU in chickens has not yet been identified. In the present study, we analyzed the effects of the central administration of NMU on food intake and hypothalamic mRNA levels of CRF, AVT and mesotocin (a nonmammalian equivalent of oxytocin) in chicks. Intracerebroventricular administration of NMU in chicks significantly suppressed food intake and induced wing-flapping behavior. NMU also significantly upregulated mRNA expression of CRF and AVT, but did not influence mRNA expression of mesotocin in the hypothalamus. These results suggest that NMU functions as an appetite-suppressive peptide via CRF and AVT in the central nervous system in chicks.

Alpha-melanocyte stimulating hormone plays an important role in the regulation of food intake by the central melanocortin system in chicks

Proopiomelanocortin (POMC, a precursor of melanocortin peptides) neurons in the hypothalamus play an important role in the central regulation of food intake in mammals. There is evidence that human melanocortin peptides alpha-, beta- and gamma2-melanocyte-stimulating hormone (α-, β- and γ2-MSH) significantly decreased food intake in chickens. However, the amino acid sequences of β- and γ2-MSH of chickens are different from those of humans whereas the amino acid sequence of α-MSH is conserved between these species. In the present study, we examined the effects of the central administration of α-, chicken β-, and chicken γ2-MSH on food intake in chicks. Central administration of α-MSH significantly suppressed food intake in chicks. In contrast, β- and γ2-MSH did not influence food intake in chicks. Central administration of HS014, a melanocortin 4 receptor antagonist, significantly reversed the anorexigenic action of α-MSH, suggesting that this action is mediated by the melanocortin 4 receptor in chicks as well as in mammals. These results suggest that α-MSH may play an important role in the regulation of food intake by the central melanocortin system in chicks.

Corticotropin-releasing factor is a downstream mediator of the beta-melanocyte-stimulating hormone-induced anorexigenic pathway in chicks.

Proopiomelanocortin (POMC, a precursor of anorexigenic neuropeptides) neurons in hypothalamus suppresses food intake in both mammals and chickens. In mammals, several lines of evidence suggest that POMC-derived anorexigenic peptides upregulate mRNA levels of anorexigenic peptides such as corticotropin-releasing factor (CRF) and thyrotropin-releasing factor and downregulate mRNA levels of orexigenic peptides such as orexin and melanin-concentrating hormone. However, the POMC-induced anorexigenic pathway in chickens has not been well characterized. In the present study, we investigated how POMC neurons regulate mechanisms of food intake using an anorexigenic peptide, beta-melanocyte-stimulating hormone (beta-MSH), derived from the post-transcriptional cleavage of POMC. Central administration of beta-MSH in chicks significantly suppressed food intake, and importantly, this suppression was accompanied by a significant upregulation of CRF mRNA levels. Furthermore, the CRF type 2 receptor antagonist alpha-helical CRF significantly reversed the anorexigenic action of beta-MSH. These findings indicate that CRF and its receptor, CRF type 2 receptor, act as the major mediators in beta-MSH-induced anorexigenic action in chicks. beta-MSH significantly increased orexin mRNA levels and did not alter mRNA levels of thyrotropin-releasing factor and melanin-concentrating hormone in chicks, suggesting that the beta-MSH-induced anorexigenic pathway in chicks is different from that in mammals. Increases in orexin mRNA levels were accompanied by significant decreases in plasma glucose concentration, suggesting that orexin mRNA might be stimulated by beta-MSH-induced hypoglycemia. Thus, this study demonstrates the direct evidence that CRF is a critical downstream target in the beta-MSH-induced anorexigenic pathway in chicks.

Effects of short term fasting on the expression of genes involved in lipid metabolism in chicks.

The aim of this study was to analyze the expression patterns of key genes involved in lipid metabolism in response to short term fasting in chicks (Gallus gallus). The mRNA level of the genes was analyzed after 0, 2, and 4 h of fasting in the liver and white adipose tissue. In the liver, the mRNA level of peroxisome proliferator-activated receptor α was significantly increased after 2 h of fasting. The mRNA levels of carnitine palmitoyltransferase 1a and acyl-CoA oxidase were significantly increased after 4 h of fasting. In contrast, the mRNA levels of sterol regulatory element-binding protein 1, acetyl-CoA carboxylase α, and fatty acid synthase were significantly decreased after 4 h of fasting. The mRNA levels of cholesterol metabolism-related genes such as 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7α-hydroxylase were significantly decreased after 4 h of fasting. In the white adipose tissue, the mRNA level of adipose triglyceride lipase was significantly increased after 4 h of fasting. In contrast, the mRNA levels of peroxisome proliferator-activated receptor γ and lipoprotein lipase were significantly decreased after 4 h of fasting. These results demonstrated that the gene expression of lipid metabolism-related genes is regulated by short term fasting in both the liver and WAT in chicks.

Intracerebroventricular administration of novel glucagon-like peptide suppresses food intake in chicks.

Glucagon-related peptides such as glucagon, glucagon-like peptide-1, and oxyntomodulin suppress food intake in mammals and birds. Recently, novel glucagon-like peptide (GCGL) was identified from chicken brain, and a comparatively high mRNA expression level of GCGL was detected in the hypothalamus. A number of studies suggest that the hypothalamus plays a critical role in the regulation of food intake in mammals and birds. In the present study, we investigated whether GCGL is involved in the central regulation of food intake in chicks. Male 8-day-old chicks (Gallus gallus) were used in all experiments. Intracerebroventricular administration of GCGL in chicks significantly suppressed food intake. Plasma glucose level was significantly decreased by GCGL, whereas plasma corticosterone level was not affected. Central administration of a corticotrophin-releasing factor (CRF) receptor antagonist, α-helical CRF, attenuated GCGL-suppressed food intake. It seems likely that CRF receptor is involved in the GCGL-induced anorexigenic pathway. All our findings suggest that GCGL functions as an anorexigenic peptide in the central nervous system of chicks.

A comparative study of the central effects of melanocortin peptides on food intake in broiler and layer chicks

Broiler chicks eat more food than layer chicks. However, the causes of the difference in food intake in the neonatal period between these strains are not clear. In this study, we examined the involvement of proopiomelanocortin (POMC)-derived melanocortin peptides α-, β- and γ-melanocyte-stimulating hormones (MSHs) in the difference in food intake between broiler and layer chicks. First, we compared the hypothalamic mRNA levels of POMC between these strains and found that there was no significant difference in these levels between broiler and layer chicks. Next, we examined the effects of central administration of MSHs on food intake in these strains. Central administration of α-MSH significantly suppressed food intake in both strains. Central administration of β-MSH significantly suppressed food intake in layer chicks, but not in broiler chicks, while central administration of γ-MSH did not influence food intake in either strain. It is therefore likely that the absence of the anorexigenic effect of β-MSH might be related to the increased food intake in broiler chicks.

Molecular Cues Guiding Matrix Stiffness in Liver Fibrosis

Tissue and matrix stiffness affect cell properties during morphogenesis, cell growth, differentiation, and migration and are altered in the tissue remodeling following injury and the pathological progression. However, detailed molecular mechanisms underlying alterations of stiffness in vivo are still poorly understood. Recent engineering technologies have developed powerful techniques to characterize the mechanical properties of cell and matrix at nanoscale levels. Extracellular matrix (ECM) influences mechanical tension and activation of pathogenic signaling during the development of chronic fibrotic diseases. In this short review, we will focus on the present knowledge of the mechanisms of how ECM stiffness is regulated during the development of liver fibrosis and the molecules involved in ECM stiffness as a potential therapeutic target for liver fibrosis.

Intracerebroventricular administration of chicken glucagon-like peptide-2 potently suppresses food intake in chicks.

Glucagon-related peptides, such as glucagon-like peptide (GLP)-1, GLP-2 and oxyntomodulin (OXM), are processed from an identical precursor proglucagon. In mammals, all of these peptides are suggested to be involved in the central regulation of food intake. We previously showed that intracerebroventricular administration of chicken OXM and GLP-1 significantly suppressed food intake in chicks. Here, we show that central administration of chicken GLP-2 potently suppresses food intake in chicks. Male 8-day-old chicks (Gallus gallus domesticus) were used in all experiments. Intracerebroventricular administration of chicken GLP-2 significantly suppressed food intake in chicks. Plasma glucose concentration was significantly decreased by chicken GLP-2, whereas plasma nonesterified fatty acid concentration was significantly increased. Intracerebroventricular administration of chicken GLP-2 did not affect plasma corticosterone concentration. In addition, the anorexigenic effect of GLP-2 was not reversed by the corticotropin-releasing factor (CRF) receptor antagonist α-helical CRF, suggesting that CRF is not a downstream mediator of the anorexigenic pathway of GLP-2 in chicks. Intracerebroventricular administration of an equimolar amount of GLP-1 and GLP-2, but not OXM, significantly suppressed food intake in both broiler and layer chicks. All our findings suggest that GLP-2 functions as a potent anorexigenic peptide in the brain, as well as GLP-1, in chicks.