Effect of glucagon-like peptide-1 and ghrelin on liver metabolites in steers

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.

Metabolomic profiling reveals differential effects of glucagon‐like peptide‐1 and insulin on nutrient partitioning in ovine liver

“…The details of liver biopsy sampling and metabolome analyses have been previously reported (El‐Sabagh et al . ). Under local anesthesia and using a 14‐gauge and 114 mm long biopsy needle (Tru‐Cut, CareFusion, Tokyo, Japan), liver biopsies (50 mg) were taken at 0, 60, 90 and 150 min to express baseline, insulin, insulin plus GLP‐1, and GLP‐1 metabolomic profiling, respectively.…”

“…Recently, hepatic metabolomic profiling revealed a contribution of GLP‐1 to lipid metabolism, oxidative stress defense and protein turnover pathways in steers, suggesting an insulin‐independent role of GLP‐1 in ruminants beyond glucose homeostasis (El‐Sabagh et al . ). Yet, this role remains unclear whether it is a direct action of GLP‐1, or indirectly mediated through its insulinotropic action (Drucker ).…”

“…Therefore, the aim of this study was to gain further insights into the insulin‐independent actions of GLP‐1 at a metabolomic level through exploring the changes in metabolic pathways involved in GLP‐1 regulation of nutrient partitioning by the liver, with the aim to draw further understanding of previous results observed (El‐Sabagh et al . , ). Identifying metabolites associated with insulin‐independent actions of GLP‐1 in ruminants would advance our understanding of the role of gut hormones in nutrient partitioning and its integration with metabolism and animal health.…”