Exogenous GLP-1 stimulates TCA cycle and suppresses gluconeogenesis and ketogenesis in late-fasted northern elephant seals pups
The postweaning fast of northern elephant seal pups is characterized by a lipid-dependent metabolism and associated with a decrease in plasma glucagon-like peptide-1 (GLP-1), insulin, and glucose and increased gluconeogenesis (GNG) and ketogenesis. We have also demonstrated that exogenous GLP-1 infu...
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ftcdlib:oai:escholarship.org:ark:/13030/qt8qm1t6rk 2023-09-05T13:19:12+02:00 Exogenous GLP-1 stimulates TCA cycle and suppresses gluconeogenesis and ketogenesis in late-fasted northern elephant seals pups Dhillon, Jaapna Viscarra, Jose A Newman, John W Fiehn, Oliver Crocker, Daniel E Ortiz, Rudy M r393 - r403 2021-04-01 application/pdf https://escholarship.org/uc/item/8qm1t6rk unknown eScholarship, University of California qt8qm1t6rk https://escholarship.org/uc/item/8qm1t6rk public AJP Regulatory Integrative and Comparative Physiology, vol 320, iss 4 Nutrition Diabetes Metabolic and endocrine Animals Biomarkers Blood Glucose Citric Acid Cycle Dose-Response Relationship Drug Fasting Glucagon-Like Peptide 1 Gluconeogenesis Infusions Intravenous Ketone Bodies Male Metabolome Metabolomics Seals Earless Time Factors Weaning adipose fatty acids glucose intolerance insulin resistance insulin sensitivity Biological Sciences Medical and Health Sciences Physiology article 2021 ftcdlib 2023-08-21T18:05:46Z The postweaning fast of northern elephant seal pups is characterized by a lipid-dependent metabolism and associated with a decrease in plasma glucagon-like peptide-1 (GLP-1), insulin, and glucose and increased gluconeogenesis (GNG) and ketogenesis. We have also demonstrated that exogenous GLP-1 infusion increased plasma insulin despite simultaneous increases in cortisol and glucagon, which collectively present contradictory regulatory stimuli of GNG, ketogenesis, and glycolysis. To assess the effects of GLP-1 on metabolism using primary carbon metabolite profiles in late-fasted seal pups, we dose-dependently infused late-fasted seals with low (LDG; 10 pM/kg; n = 3) or high (HDG; 100 pM/kg; n = 4) GLP-1 immediately following a glucose bolus (0.5 g/kg), using glucose without GLP-1 as control (n = 5). Infusions were performed in similarly aged animals 6-8 wk into their postweaning fast. The plasma metabolome was measured from samples collected at five time points just prior to and during the infusions, and network maps constructed to robustly evaluate the effects of GLP-1 on primary carbon metabolism. HDG increased key tricarboxylic acid (TCA) cycle metabolites, and decreased phosphoenolpyruvate and acetoacetate (P < 0.05) suggesting that elevated levels of GLP-1 promote glycolysis and suppress GNG and ketogenesis, which collectively increase glucose clearance. These GLP-1-mediated effects on cellular metabolism help to explain why plasma GLP-1 concentrations decrease naturally in fasting pups as an evolved mechanism to help conserve glucose during the late-fasting period. Article in Journal/Newspaper Elephant Seal Elephant Seals University of California: eScholarship |
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Open Polar |
collection |
University of California: eScholarship |
op_collection_id |
ftcdlib |
language |
unknown |
topic |
Nutrition Diabetes Metabolic and endocrine Animals Biomarkers Blood Glucose Citric Acid Cycle Dose-Response Relationship Drug Fasting Glucagon-Like Peptide 1 Gluconeogenesis Infusions Intravenous Ketone Bodies Male Metabolome Metabolomics Seals Earless Time Factors Weaning adipose fatty acids glucose intolerance insulin resistance insulin sensitivity Biological Sciences Medical and Health Sciences Physiology |
spellingShingle |
Nutrition Diabetes Metabolic and endocrine Animals Biomarkers Blood Glucose Citric Acid Cycle Dose-Response Relationship Drug Fasting Glucagon-Like Peptide 1 Gluconeogenesis Infusions Intravenous Ketone Bodies Male Metabolome Metabolomics Seals Earless Time Factors Weaning adipose fatty acids glucose intolerance insulin resistance insulin sensitivity Biological Sciences Medical and Health Sciences Physiology Dhillon, Jaapna Viscarra, Jose A Newman, John W Fiehn, Oliver Crocker, Daniel E Ortiz, Rudy M Exogenous GLP-1 stimulates TCA cycle and suppresses gluconeogenesis and ketogenesis in late-fasted northern elephant seals pups |
topic_facet |
Nutrition Diabetes Metabolic and endocrine Animals Biomarkers Blood Glucose Citric Acid Cycle Dose-Response Relationship Drug Fasting Glucagon-Like Peptide 1 Gluconeogenesis Infusions Intravenous Ketone Bodies Male Metabolome Metabolomics Seals Earless Time Factors Weaning adipose fatty acids glucose intolerance insulin resistance insulin sensitivity Biological Sciences Medical and Health Sciences Physiology |
description |
The postweaning fast of northern elephant seal pups is characterized by a lipid-dependent metabolism and associated with a decrease in plasma glucagon-like peptide-1 (GLP-1), insulin, and glucose and increased gluconeogenesis (GNG) and ketogenesis. We have also demonstrated that exogenous GLP-1 infusion increased plasma insulin despite simultaneous increases in cortisol and glucagon, which collectively present contradictory regulatory stimuli of GNG, ketogenesis, and glycolysis. To assess the effects of GLP-1 on metabolism using primary carbon metabolite profiles in late-fasted seal pups, we dose-dependently infused late-fasted seals with low (LDG; 10 pM/kg; n = 3) or high (HDG; 100 pM/kg; n = 4) GLP-1 immediately following a glucose bolus (0.5 g/kg), using glucose without GLP-1 as control (n = 5). Infusions were performed in similarly aged animals 6-8 wk into their postweaning fast. The plasma metabolome was measured from samples collected at five time points just prior to and during the infusions, and network maps constructed to robustly evaluate the effects of GLP-1 on primary carbon metabolism. HDG increased key tricarboxylic acid (TCA) cycle metabolites, and decreased phosphoenolpyruvate and acetoacetate (P < 0.05) suggesting that elevated levels of GLP-1 promote glycolysis and suppress GNG and ketogenesis, which collectively increase glucose clearance. These GLP-1-mediated effects on cellular metabolism help to explain why plasma GLP-1 concentrations decrease naturally in fasting pups as an evolved mechanism to help conserve glucose during the late-fasting period. |
format |
Article in Journal/Newspaper |
author |
Dhillon, Jaapna Viscarra, Jose A Newman, John W Fiehn, Oliver Crocker, Daniel E Ortiz, Rudy M |
author_facet |
Dhillon, Jaapna Viscarra, Jose A Newman, John W Fiehn, Oliver Crocker, Daniel E Ortiz, Rudy M |
author_sort |
Dhillon, Jaapna |
title |
Exogenous GLP-1 stimulates TCA cycle and suppresses gluconeogenesis and ketogenesis in late-fasted northern elephant seals pups |
title_short |
Exogenous GLP-1 stimulates TCA cycle and suppresses gluconeogenesis and ketogenesis in late-fasted northern elephant seals pups |
title_full |
Exogenous GLP-1 stimulates TCA cycle and suppresses gluconeogenesis and ketogenesis in late-fasted northern elephant seals pups |
title_fullStr |
Exogenous GLP-1 stimulates TCA cycle and suppresses gluconeogenesis and ketogenesis in late-fasted northern elephant seals pups |
title_full_unstemmed |
Exogenous GLP-1 stimulates TCA cycle and suppresses gluconeogenesis and ketogenesis in late-fasted northern elephant seals pups |
title_sort |
exogenous glp-1 stimulates tca cycle and suppresses gluconeogenesis and ketogenesis in late-fasted northern elephant seals pups |
publisher |
eScholarship, University of California |
publishDate |
2021 |
url |
https://escholarship.org/uc/item/8qm1t6rk |
op_coverage |
r393 - r403 |
genre |
Elephant Seal Elephant Seals |
genre_facet |
Elephant Seal Elephant Seals |
op_source |
AJP Regulatory Integrative and Comparative Physiology, vol 320, iss 4 |
op_relation |
qt8qm1t6rk https://escholarship.org/uc/item/8qm1t6rk |
op_rights |
public |
_version_ |
1776200019423002624 |