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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/41f40433dd3746cc9e1643b336bd45ae
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spelling	oai:doaj.org-article:41f40433dd3746cc9e1643b336bd45ae2021-12-02T18:51:52ZFree fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation10.1038/s41598-021-95750-92045-2322https://doaj.org/article/41f40433dd3746cc9e1643b336bd45ae2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95750-9https://doaj.org/toc/2045-2322Abstract 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.Julia HummelLouise FritscheAndreas VosselerCorinna DanneckerMiriam HoeneKonstantinos KantartzisHans-Ulrich HäringNorbert StefanJürgen MachannAndreas L. BirkenfeldCora WeigertRobert WagnerAndreas PeterAndreas FritscheMartin HeniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/41f40433dd3746cc9e1643b336bd45ae
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Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation

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