Effect of glucagon-like peptide-1 and ghrelin on liver metabolites in steers
M. El-Sabagh A B , D. Taniguchi A , T. Sugino A C , T. Obitsu A and K. Taniguchi AA Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8528, Japan.
B Permanent address: Faculty of Veterinary Medicine, Kafrelsheikh University, 33516, Kafr El-Sheikh, Egypt.
C Corresponding author. Email: sugino@hiroshima-u.ac.jp
Animal Production Science 54(10) 1732-1736 https://doi.org/10.1071/AN14363
Submitted: 13 March 2014 Accepted: 23 June 2014 Published: 19 August 2014
Abstract
Glucagon-like peptide 1 (GLP-1) and ghrelin have opposite regulatory effects on glucose metabolism in non-ruminants. However, mechanisms by which GLP-1 and ghrelin regulate nutrient partitioning, particularly in the liver, have been much less demonstrated in ruminants. A novel metabolomic method based on capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) combined with multivariate statistical analysis was applied to address the GLP-1 and ghrelin-induced metabolic changes in the liver of steers. Three Holstein steers (400 ± 5.0 kg LW) fed a maintenance diet according to Japanese feeding standards were randomly assigned to three treatments (GLP-1, ghrelin and saline) in a 3 × 3 Latin square design with one week apart. Liver biopsies were taken 30 min after a single injection (1.0 μg/kg LW) of GLP-1 or ghrelin, and analysed for metabolites by Agilent CE-TOFMS system. Also, blood samples were collected for plasma hormones analysis. Results indicated that 20 and 10 liver metabolites were altered (P < 0.05) by GLP-1 and ghrelin, respectively. Pathway analysis showed that GLP-1 is involved in biochemical pathways related to glycolysis/gluconeogenesis, lipogenesis and lipid export from the liver, oxidative stress defence and protein turnover. Ghrelin was shown to be involved in pathways related to glycolysis, protein anabolism and phospholipid biosynthesis. However, plasma concentrations of insulin, growth hormone and glucagon did not differ between treatments. These results imply that GLP-1 and ghrelin are involved in multibiochemical pathways that go beyond simply regulating glucose metabolism. In addition, the effects of GLP-1 and ghrelin may potentially be independent of insulin and growth hormone, respectively.
Additional keywords: bioinformatics, biomarkers, metabolomics, nutrient partitioning.
References
Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132, 2131–2157.| Biology of incretins: GLP-1 and GIP.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXmsVynsrY%3D&md5=85f093b9f61a757f6601fb52ef050162CAS | 17498508PubMed |
Circu ML, Aw TY (2012) Glutathione and modulation of cell apoptosis. Biochimica et Biophysica Acta 1823, 1767–1777.
| Glutathione and modulation of cell apoptosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtlSnsrvP&md5=494fa9274cb5e4f97131f8d870b325d2CAS | 22732297PubMed |
Deutsch JC (1998) Spontaneous hydrolysis and dehydration of dehydroascorbic acid in aqueous solution. Analytical Biochemistry 260, 223–229.
| Spontaneous hydrolysis and dehydration of dehydroascorbic acid in aqueous solution.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXks1yltro%3D&md5=e9bfc46c9c568e1ec352dd0ce1bc2f84CAS | 9657882PubMed |
Dezaki K (2013) Ghrelin function in insulin release and glucose metabolism. Endocrine Development 25, 135–143.
| Ghrelin function in insulin release and glucose metabolism.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtlWksL3P&md5=84bd323c6f6dcb66aec28bea9534a4dfCAS | 23652399PubMed |
Forbes JM (2007) Metabolites and hormones. In ‘Voluntary food intake and diet selection in farm animals’. 2nd edn. (Ed. JM Forbes) pp. 69–90. (CAB International: Wallingford, UK)
Fukumori R, Sugino T, Shingu H, Moriya N, Hasegawa Y, Kojima M, Kangawa K, Obitsu T, Kushibiki S, Taniguchi K (2012) Effects of calcium salts of long-chain fatty acids and rumen-protected methionine on plasma concentrations of ghrelin, glucagon-like peptide-1 (7 to 36) amide and pancreatic hormones in lactating cows. Domestic Animal Endocrinology 42, 74–82.
| Effects of calcium salts of long-chain fatty acids and rumen-protected methionine on plasma concentrations of ghrelin, glucagon-like peptide-1 (7 to 36) amide and pancreatic hormones in lactating cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XmtFCruw%3D%3D&md5=9519587774bd74a83bcb3411e77ec294CAS | 22056209PubMed |
Hartman PE, Hartman Z, Ault KT (1990) Scavenging of singlet molecular oxygen by imidazole compounds: high and sustained activities of carboxy terminal histidine dipeptides and exceptional activity of imidazole-4-acetic acid. Photochemistry and Photobiology 51, 59–66.
| Scavenging of singlet molecular oxygen by imidazole compounds: high and sustained activities of carboxy terminal histidine dipeptides and exceptional activity of imidazole-4-acetic acid.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXhslChtLs%3D&md5=a55162b50e7db27c026674b07363708bCAS | 2304979PubMed |
Jennings JS, Wertz-Lutz AE, Pritchard RH, Weaver AD, Keisler DH, Bruns K (2011) Circulating ghrelin and leptin concentrations and growth hormone secretagogue receptor abundance in liver, muscle, and adipose tissue of beef cattle exhibiting differences in composition of gain. Journal of Animal Science 89, 3954–3972.
| Circulating ghrelin and leptin concentrations and growth hormone secretagogue receptor abundance in liver, muscle, and adipose tissue of beef cattle exhibiting differences in composition of gain.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhs1Sqtb3M&md5=5628e87ee0a20a4967f4e39f0250fc48CAS | 21724941PubMed |
Junker BH, Klukas C, Schreiber F (2006) VANTED: a system for advanced data analysis and visualization in the context of biological networks. BMC Bioinformatics 7, 109
| VANTED: a system for advanced data analysis and visualization in the context of biological networks.Crossref | GoogleScholarGoogle Scholar | 16519817PubMed |
Mahfouz MM, Zhou SQ, Kummerow FA (2009) Vitamin B6 compounds are capable of reducing the superoxide radical and lipid peroxide levels induced by H2O2 in vascular endothelial cells in culture. International Journal for Vitamin and Nutrition Research 79, 218–229.
| Vitamin B6 compounds are capable of reducing the superoxide radical and lipid peroxide levels induced by H2O2 in vascular endothelial cells in culture.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXktVSls7s%3D&md5=904434a92240ceedb4be6fe6f5176ccbCAS | 20209473PubMed |
NARO (2009) ‘Japanese feeding standard for beef cattle.’ (Japan Livestock Industry Association: Tokyo)
Nissim I, Yudkoff M, Brosnan JT (1996) Regulation of [15N]urea synthesis from [5–15N]glutamine. Role of pH, hormones, and pyruvate. The Journal of Biological Chemistry 271, 31 234–31 242.
| Regulation of [15N]urea synthesis from [5–15N]glutamine. Role of pH, hormones, and pyruvate.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28Xns1ajsbY%3D&md5=2ae3548205d03f73c73bd40c2e646830CAS |
Noga AA, Vance DE (2003) A gender-specific role for phosphatidylethanolamine N-methyltransferasederived phosphatidylcholine in the regulation of plasma high density and very low density lipoproteins in mice. The Journal of Biological Chemistry 278, 21851–21859.
| A gender-specific role for phosphatidylethanolamine N-methyltransferasederived phosphatidylcholine in the regulation of plasma high density and very low density lipoproteins in mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXksVemtrc%3D&md5=ce017da6f1f3dcf43ae1b5dece5eaf0dCAS | 12668679PubMed |
Pezeshki A, Muench GP, Chelikani PK (2012) Expression of peptide YY, proglucagon, neuropeptide Y receptor Y2, and glucagon-like peptide-1 receptor in bovine peripheral tissues. Journal of Dairy Science 95, 5089–5094.
| Expression of peptide YY, proglucagon, neuropeptide Y receptor Y2, and glucagon-like peptide-1 receptor in bovine peripheral tissues.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xht1emsLnP&md5=c4e947cd08497b5a731735486bb3f4f8CAS | 22916913PubMed |
Sha W, da Costa KA, Fischer LM (2010) Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline. The Journal of the Federation of American Societies for Experimental Biology 24, 2962–2975.
| Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtVeitr%2FN&md5=4667c0608b0f99076a21015ed172380bCAS |
Soga T, Baran R, Suematsu M, Ueno Y, Ikeda S, Sakurakawa T, Kakazu Y, Ishikawa T, Robert M, Nishioka T, Tomita M (2006) Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption. The Journal of Biological Chemistry 281, 16768–16776.
| Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XlsV2ltLo%3D&md5=37e4ed011756e90eb01c17ab929f82e6CAS | 16608839PubMed |
Soga T, Ishikawa T, Igarashi S, Sugawara K, Kakazu Y, Tomita M (2007) Analysis of nucleotides by pressure-assisted capillary electrophoresis–mass spectrometry using silanol mask technique. Journal of Chromatography. A 1159, 125–133.
| Analysis of nucleotides by pressure-assisted capillary electrophoresis–mass spectrometry using silanol mask technique.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXnslGgt7g%3D&md5=6de4acd96e68c934a0d1ff7aaf0239d4CAS | 17543971PubMed |
Steinert RE, Feinle-Bisset C, Geary N, Beglinger C (2013) Digestive physiology of the pig symposium: secretion of gastrointestinal hormones and eating control. Journal of Animal Science 91, 1963–1973.
| Digestive physiology of the pig symposium: secretion of gastrointestinal hormones and eating control.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXotl2gsro%3D&md5=01fa6dc525eb414c8b83e4a9b2353796CAS | 23307852PubMed |
Wu G (2013) ‘Amino acids biochemistry and nutrition.’ (CRC Press, Taylor & Francis Group: New York)
Zeisel SH (2006) Choline: critical role during fetal development and dietary requirements in adults. Annual Review of Nutrition 26, 229–250.
| Choline: critical role during fetal development and dietary requirements in adults.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xpt1Cltr4%3D&md5=5ee1169fd4eb49dd1a0221dc5836b368CAS | 16848706PubMed |
