Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance.
Prolonged fasting in northern elephant seals (NES) is characterized by a reliance on lipid metabolism, conservation of protein, and reduced plasma insulin. During early fasting, glucose infusion previously reduced plasma free fatty acids (FFA); however, during late-fasting, it induced an atypical el...
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eScholarship, University of California
2017
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ftcdlib:oai:escholarship.org:ark:/13030/qt3x70w0hv 2024-09-15T18:04:44+00:00 Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance. Olmstead, Keedrian I La Frano, Michael R Fahrmann, Johannes Grapov, Dmitry Viscarra, Jose A Newman, John W Fiehn, Oliver Crocker, Daniel E Filipp, Fabian V Ortiz, Rudy M 60 2017-05-01 application/pdf https://escholarship.org/uc/item/3x70w0hv https://escholarship.org/content/qt3x70w0hv/qt3x70w0hv.pdf https://doi.org/10.1007/s11306-017-1186-y unknown eScholarship, University of California qt3x70w0hv https://escholarship.org/uc/item/3x70w0hv https://escholarship.org/content/qt3x70w0hv/qt3x70w0hv.pdf doi:10.1007/s11306-017-1186-y public Metabolomics : Official journal of the Metabolomic Society, vol 13, iss 5 Endocannabinoids Fatty acids Lipidomics Metabolomics Substrate metabolism Nutrition Diabetes Obesity Metabolic and endocrine Analytical Chemistry Biochemistry and Cell Biology Clinical Sciences article 2017 ftcdlib https://doi.org/10.1007/s11306-017-1186-y 2024-06-28T06:28:21Z Prolonged fasting in northern elephant seals (NES) is characterized by a reliance on lipid metabolism, conservation of protein, and reduced plasma insulin. During early fasting, glucose infusion previously reduced plasma free fatty acids (FFA); however, during late-fasting, it induced an atypical elevation in FFA despite comparable increases in insulin during both periods suggestive of a dynamic shift in tissue responsiveness to glucose-stimulated insulin secretion. To better assess the contribution of insulin to this fasting-associated shift in substrate metabolism. We compared the responses of plasma metabolites (amino acids (AA), FFA, endocannabinoids (EC), and primary carbon metabolites (PCM)) to an insulin infusion (65 mU/kg) in early- and late-fasted NES pups (n = 5/group). Plasma samples were collected prior to infusion (T0) and at 10, 30, 60, and 120 min post-infusion, and underwent untargeted and targeted metabolomics analyses utilizing a variety of GC-MS and LC-MS technologies. In early fasting, the majority (72%) of metabolite trajectories return to baseline levels within 2 h, but not in late fasting indicative of an increase in tissue sensitivity to insulin. In late-fasting, increases in FFA and ketone pools, coupled with decreases in AA and PCM, indicate a shift toward lipolysis, beta-oxidation, ketone metabolism, and decreased protein catabolism. Conversely, insulin increased PCM AUC in late fasting suggesting that gluconeogenic pathways are activated. Insulin also decreased FFA AUC between early and late fasting suggesting that insulin suppresses triglyceride hydrolysis. Naturally adapted tolerance to prolonged fasting in these mammals is likely accomplished by suppressing insulin levels and activity, providing novel insight on the evolution of insulin during a condition of temporary, reversible insulin resistance. Article in Journal/Newspaper Elephant Seals University of California: eScholarship Metabolomics 13 5 |
institution |
Open Polar |
collection |
University of California: eScholarship |
op_collection_id |
ftcdlib |
language |
unknown |
topic |
Endocannabinoids Fatty acids Lipidomics Metabolomics Substrate metabolism Nutrition Diabetes Obesity Metabolic and endocrine Analytical Chemistry Biochemistry and Cell Biology Clinical Sciences |
spellingShingle |
Endocannabinoids Fatty acids Lipidomics Metabolomics Substrate metabolism Nutrition Diabetes Obesity Metabolic and endocrine Analytical Chemistry Biochemistry and Cell Biology Clinical Sciences Olmstead, Keedrian I La Frano, Michael R Fahrmann, Johannes Grapov, Dmitry Viscarra, Jose A Newman, John W Fiehn, Oliver Crocker, Daniel E Filipp, Fabian V Ortiz, Rudy M Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance. |
topic_facet |
Endocannabinoids Fatty acids Lipidomics Metabolomics Substrate metabolism Nutrition Diabetes Obesity Metabolic and endocrine Analytical Chemistry Biochemistry and Cell Biology Clinical Sciences |
description |
Prolonged fasting in northern elephant seals (NES) is characterized by a reliance on lipid metabolism, conservation of protein, and reduced plasma insulin. During early fasting, glucose infusion previously reduced plasma free fatty acids (FFA); however, during late-fasting, it induced an atypical elevation in FFA despite comparable increases in insulin during both periods suggestive of a dynamic shift in tissue responsiveness to glucose-stimulated insulin secretion. To better assess the contribution of insulin to this fasting-associated shift in substrate metabolism. We compared the responses of plasma metabolites (amino acids (AA), FFA, endocannabinoids (EC), and primary carbon metabolites (PCM)) to an insulin infusion (65 mU/kg) in early- and late-fasted NES pups (n = 5/group). Plasma samples were collected prior to infusion (T0) and at 10, 30, 60, and 120 min post-infusion, and underwent untargeted and targeted metabolomics analyses utilizing a variety of GC-MS and LC-MS technologies. In early fasting, the majority (72%) of metabolite trajectories return to baseline levels within 2 h, but not in late fasting indicative of an increase in tissue sensitivity to insulin. In late-fasting, increases in FFA and ketone pools, coupled with decreases in AA and PCM, indicate a shift toward lipolysis, beta-oxidation, ketone metabolism, and decreased protein catabolism. Conversely, insulin increased PCM AUC in late fasting suggesting that gluconeogenic pathways are activated. Insulin also decreased FFA AUC between early and late fasting suggesting that insulin suppresses triglyceride hydrolysis. Naturally adapted tolerance to prolonged fasting in these mammals is likely accomplished by suppressing insulin levels and activity, providing novel insight on the evolution of insulin during a condition of temporary, reversible insulin resistance. |
format |
Article in Journal/Newspaper |
author |
Olmstead, Keedrian I La Frano, Michael R Fahrmann, Johannes Grapov, Dmitry Viscarra, Jose A Newman, John W Fiehn, Oliver Crocker, Daniel E Filipp, Fabian V Ortiz, Rudy M |
author_facet |
Olmstead, Keedrian I La Frano, Michael R Fahrmann, Johannes Grapov, Dmitry Viscarra, Jose A Newman, John W Fiehn, Oliver Crocker, Daniel E Filipp, Fabian V Ortiz, Rudy M |
author_sort |
Olmstead, Keedrian I |
title |
Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance. |
title_short |
Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance. |
title_full |
Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance. |
title_fullStr |
Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance. |
title_full_unstemmed |
Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance. |
title_sort |
insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance. |
publisher |
eScholarship, University of California |
publishDate |
2017 |
url |
https://escholarship.org/uc/item/3x70w0hv https://escholarship.org/content/qt3x70w0hv/qt3x70w0hv.pdf https://doi.org/10.1007/s11306-017-1186-y |
op_coverage |
60 |
genre |
Elephant Seals |
genre_facet |
Elephant Seals |
op_source |
Metabolomics : Official journal of the Metabolomic Society, vol 13, iss 5 |
op_relation |
qt3x70w0hv https://escholarship.org/uc/item/3x70w0hv https://escholarship.org/content/qt3x70w0hv/qt3x70w0hv.pdf doi:10.1007/s11306-017-1186-y |
op_rights |
public |
op_doi |
https://doi.org/10.1007/s11306-017-1186-y |
container_title |
Metabolomics |
container_volume |
13 |
container_issue |
5 |
_version_ |
1810442350193803264 |