Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation

Abstract The selection of carbohydrates or fat to generate intracellular energy is thought to be crucial for long-term metabolic health. While most studies assess fuel selection after a metabolic challenge, the determinants of substrate oxidation in the fasted state remain largely unexplored. We the...

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Main Authors: Julia Hummel, Louise Fritsche, Andreas Vosseler, Corinna Dannecker, Miriam Hoene, Konstantinos Kantartzis, Hans-Ulrich Häring, Norbert Stefan, Jürgen Machann, Andreas L. Birkenfeld, Cora Weigert, Robert Wagner, Andreas Peter, Andreas Fritsche, Martin Heni
Format: Article
Language:English
Published: Nature Portfolio 2021-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-95750-9
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author Julia Hummel
Louise Fritsche
Andreas Vosseler
Corinna Dannecker
Miriam Hoene
Konstantinos Kantartzis
Hans-Ulrich Häring
Norbert Stefan
Jürgen Machann
Andreas L. Birkenfeld
Cora Weigert
Robert Wagner
Andreas Peter
Andreas Fritsche
Martin Heni
author_facet Julia Hummel
Louise Fritsche
Andreas Vosseler
Corinna Dannecker
Miriam Hoene
Konstantinos Kantartzis
Hans-Ulrich Häring
Norbert Stefan
Jürgen Machann
Andreas L. Birkenfeld
Cora Weigert
Robert Wagner
Andreas Peter
Andreas Fritsche
Martin Heni
author_sort Julia Hummel
collection DOAJ
description Abstract The selection of carbohydrates or fat to generate intracellular energy is thought to be crucial for long-term metabolic health. While most studies assess fuel selection after a metabolic challenge, the determinants of substrate oxidation in the fasted state remain largely unexplored. We therefore assessed the respiratory quotient by indirect calorimetry as a read-out for substrate oxidation following an overnight fast. This cross-sectional analysis consisted of 192 (92 women, 100 men) either lean or obese participants. Following an overnight fast, the respiratory quotient (RQ) was assessed, after which a 5-point 75-g oral glucose tolerance test was performed. Unlike glucose and insulin, fasting free fatty acids (FFA) correlated negatively with fasting RQ (p < 0.0001). Participants with high levels of the ketone body β-hydroxybutyric acid had significantly lower RQ values. Fasting levels of glucose-dependent insulinotropic polypeptide (GIP) and glicentin were positively associated with fasting RQ (all p ≤ 0.03), whereas GLP-1 showed no significant association. Neither BMI, nor total body fat, nor body fat distribution correlated with fasting RQ. No relationship between the RQ and diabetes or the metabolic syndrome could be observed. In the fasting state, FFA concentrations were strongly linked to the preferentially oxidized substrate. Our data did not indicate any relationship between fasting substrate oxidation and metabolic diseases, including obesity, diabetes, and the metabolic syndrome. Since glicentin and GIP are linked to fuel selection in the fasting state, novel therapeutic approaches that target these hormones may have the potential to modulate substrate oxidation.
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spelling doaj.art-41f40433dd3746cc9e1643b336bd45ae2022-12-21T22:59:52ZengNature PortfolioScientific Reports2045-23222021-08-011111910.1038/s41598-021-95750-9Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidationJulia Hummel0Louise Fritsche1Andreas Vosseler2Corinna Dannecker3Miriam Hoene4Konstantinos Kantartzis5Hans-Ulrich Häring6Norbert Stefan7Jürgen Machann8Andreas L. Birkenfeld9Cora Weigert10Robert Wagner11Andreas Peter12Andreas Fritsche13Martin Heni14Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, Eberhard Karls University TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of TübingenAbstract The selection of carbohydrates or fat to generate intracellular energy is thought to be crucial for long-term metabolic health. While most studies assess fuel selection after a metabolic challenge, the determinants of substrate oxidation in the fasted state remain largely unexplored. We therefore assessed the respiratory quotient by indirect calorimetry as a read-out for substrate oxidation following an overnight fast. This cross-sectional analysis consisted of 192 (92 women, 100 men) either lean or obese participants. Following an overnight fast, the respiratory quotient (RQ) was assessed, after which a 5-point 75-g oral glucose tolerance test was performed. Unlike glucose and insulin, fasting free fatty acids (FFA) correlated negatively with fasting RQ (p < 0.0001). Participants with high levels of the ketone body β-hydroxybutyric acid had significantly lower RQ values. Fasting levels of glucose-dependent insulinotropic polypeptide (GIP) and glicentin were positively associated with fasting RQ (all p ≤ 0.03), whereas GLP-1 showed no significant association. Neither BMI, nor total body fat, nor body fat distribution correlated with fasting RQ. No relationship between the RQ and diabetes or the metabolic syndrome could be observed. In the fasting state, FFA concentrations were strongly linked to the preferentially oxidized substrate. Our data did not indicate any relationship between fasting substrate oxidation and metabolic diseases, including obesity, diabetes, and the metabolic syndrome. Since glicentin and GIP are linked to fuel selection in the fasting state, novel therapeutic approaches that target these hormones may have the potential to modulate substrate oxidation.https://doi.org/10.1038/s41598-021-95750-9
spellingShingle Julia Hummel
Louise Fritsche
Andreas Vosseler
Corinna Dannecker
Miriam Hoene
Konstantinos Kantartzis
Hans-Ulrich Häring
Norbert Stefan
Jürgen Machann
Andreas L. Birkenfeld
Cora Weigert
Robert Wagner
Andreas Peter
Andreas Fritsche
Martin Heni
Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation
Scientific Reports
title Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation
title_full Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation
title_fullStr Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation
title_full_unstemmed Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation
title_short Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation
title_sort free fatty acids glicentin and glucose dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation
url https://doi.org/10.1038/s41598-021-95750-9
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