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Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates

OBJECTIVE: Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be...

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Autores principales: Lundsgaard, Anne-Marie, Fritzen, Andreas M., Sjøberg, Kim A., Myrmel, Lene S., Madsen, Lise, Wojtaszewski, Jørgen F.P., Richter, Erik A., Kiens, Bente
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220397/
https://www.ncbi.nlm.nih.gov/pubmed/28123934
http://dx.doi.org/10.1016/j.molmet.2016.11.001
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author Lundsgaard, Anne-Marie
Fritzen, Andreas M.
Sjøberg, Kim A.
Myrmel, Lene S.
Madsen, Lise
Wojtaszewski, Jørgen F.P.
Richter, Erik A.
Kiens, Bente
author_facet Lundsgaard, Anne-Marie
Fritzen, Andreas M.
Sjøberg, Kim A.
Myrmel, Lene S.
Madsen, Lise
Wojtaszewski, Jørgen F.P.
Richter, Erik A.
Kiens, Bente
author_sort Lundsgaard, Anne-Marie
collection PubMed
description OBJECTIVE: Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be increased to meet eucaloric balance. This raises the possibility that intake of a diet rich in carbohydrates may induce an increase in plasma FGF21 levels per se. Here we studied the role of dietary carbohydrates on the levels of circulating FGF21 and concomitant physiologic effects by feeding healthy men a carbohydrate rich diet without reducing protein intake. METHODS: A diet enriched in carbohydrates (80 E% carbohydrate; CHO) and a eucaloric control diet (CON) were provided to nine healthy men for three days. The energy intake during the CHO diet was increased (+75% energy) to ensure similar dietary protein intake in CHO and CON. To control for the effect of caloric surplus, we similarly overfed (+75% energy) the same subjects for three days with a fat-rich diet (78 E% fat; FAT), consisting of primarily unsaturated fatty acids. The three diets were provided in random order. RESULTS: After CHO, plasma FGF21 concentration increased 8-fold compared to CON (329 ± 99 vs. 39 ± 9 pg ml(−1), p < 0.05). In contrast, after FAT only a non-significant tendency (p = 0.073) to an increase in plasma FGF21 concentration was found. The increase in FGF21 concentration after CHO correlated closely (r = 0.88, p < 0.01) with increased leg glucose uptake (62%, p < 0.05) and increased hepatic glucose production (17%, p < 0.01), indicating increased glucose turnover. Plasma fatty acid (FA) concentration was decreased by 68% (p < 0.01), supported by reduced subcutaneous adipose tissue HSL Ser(660) phosphorylation (p < 0.01) and perilipin 1 protein content (p < 0.01), pointing to a suppression of adipose tissue lipolysis. Concomitantly, a 146% increase in the plasma marker of hepatic de novo lipogenesis C16:1 n−7 FA (p < 0.01) was observed together with 101% increased plasma TG concentration (p < 0.001) in association with CHO intake and increased plasma FGF21 concentration. CONCLUSION: Excess dietary carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais.
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spelling pubmed-52203972017-01-25 Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates Lundsgaard, Anne-Marie Fritzen, Andreas M. Sjøberg, Kim A. Myrmel, Lene S. Madsen, Lise Wojtaszewski, Jørgen F.P. Richter, Erik A. Kiens, Bente Mol Metab Brief Communication OBJECTIVE: Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be increased to meet eucaloric balance. This raises the possibility that intake of a diet rich in carbohydrates may induce an increase in plasma FGF21 levels per se. Here we studied the role of dietary carbohydrates on the levels of circulating FGF21 and concomitant physiologic effects by feeding healthy men a carbohydrate rich diet without reducing protein intake. METHODS: A diet enriched in carbohydrates (80 E% carbohydrate; CHO) and a eucaloric control diet (CON) were provided to nine healthy men for three days. The energy intake during the CHO diet was increased (+75% energy) to ensure similar dietary protein intake in CHO and CON. To control for the effect of caloric surplus, we similarly overfed (+75% energy) the same subjects for three days with a fat-rich diet (78 E% fat; FAT), consisting of primarily unsaturated fatty acids. The three diets were provided in random order. RESULTS: After CHO, plasma FGF21 concentration increased 8-fold compared to CON (329 ± 99 vs. 39 ± 9 pg ml(−1), p < 0.05). In contrast, after FAT only a non-significant tendency (p = 0.073) to an increase in plasma FGF21 concentration was found. The increase in FGF21 concentration after CHO correlated closely (r = 0.88, p < 0.01) with increased leg glucose uptake (62%, p < 0.05) and increased hepatic glucose production (17%, p < 0.01), indicating increased glucose turnover. Plasma fatty acid (FA) concentration was decreased by 68% (p < 0.01), supported by reduced subcutaneous adipose tissue HSL Ser(660) phosphorylation (p < 0.01) and perilipin 1 protein content (p < 0.01), pointing to a suppression of adipose tissue lipolysis. Concomitantly, a 146% increase in the plasma marker of hepatic de novo lipogenesis C16:1 n−7 FA (p < 0.01) was observed together with 101% increased plasma TG concentration (p < 0.001) in association with CHO intake and increased plasma FGF21 concentration. CONCLUSION: Excess dietary carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais. Elsevier 2016-11-16 /pmc/articles/PMC5220397/ /pubmed/28123934 http://dx.doi.org/10.1016/j.molmet.2016.11.001 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Brief Communication
Lundsgaard, Anne-Marie
Fritzen, Andreas M.
Sjøberg, Kim A.
Myrmel, Lene S.
Madsen, Lise
Wojtaszewski, Jørgen F.P.
Richter, Erik A.
Kiens, Bente
Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates
title Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates
title_full Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates
title_fullStr Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates
title_full_unstemmed Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates
title_short Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates
title_sort circulating fgf21 in humans is potently induced by short term overfeeding of carbohydrates
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220397/
https://www.ncbi.nlm.nih.gov/pubmed/28123934
http://dx.doi.org/10.1016/j.molmet.2016.11.001
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