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Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates.
Mol Metab 2017; 6(1):22-29MM

Abstract

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 Ser660 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.

Authors+Show Affiliations

Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.National Institute of Nutrition and Seafood Research, Bergen, Norway.National Institute of Nutrition and Seafood Research, Bergen, Norway; Laboratory of Genomics and Molecular Biomedicine, Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark. Electronic address: bkiens@nexs.ku.dk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28123934

Citation

Lundsgaard, Anne-Marie, et al. "Circulating FGF21 in Humans Is Potently Induced By Short Term Overfeeding of Carbohydrates." Molecular Metabolism, vol. 6, no. 1, 2017, pp. 22-29.
Lundsgaard AM, Fritzen AM, Sjøberg KA, et al. Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates. Mol Metab. 2017;6(1):22-29.
Lundsgaard, A. M., Fritzen, A. M., Sjøberg, K. A., Myrmel, L. S., Madsen, L., Wojtaszewski, J. F. P., ... Kiens, B. (2017). Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates. Molecular Metabolism, 6(1), pp. 22-29. doi:10.1016/j.molmet.2016.11.001.
Lundsgaard AM, et al. Circulating FGF21 in Humans Is Potently Induced By Short Term Overfeeding of Carbohydrates. Mol Metab. 2017;6(1):22-29. PubMed PMID: 28123934.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates. AU - Lundsgaard,Anne-Marie, AU - Fritzen,Andreas M, AU - Sjøberg,Kim A, AU - Myrmel,Lene S, AU - Madsen,Lise, AU - Wojtaszewski,Jørgen F P, AU - Richter,Erik A, AU - Kiens,Bente, Y1 - 2016/11/16/ PY - 2016/10/04/received PY - 2016/11/07/revised PY - 2016/11/09/accepted PY - 2017/1/27/entrez PY - 2017/1/27/pubmed PY - 2018/10/3/medline KW - AMPK, AMP-activated kinase KW - ATGL, adipose triglyceride lipase KW - BCA, bicinchoninic acid KW - BM, body mass KW - BMI, body mass index KW - CHO, carbohydrate-rich diet KW - CON, control diet KW - Carbohydrates KW - ChREBP, carbohydrate-responsive element binding protein KW - Diet KW - FA, fatty acid KW - FAT, fat-rich diet KW - FGF21 KW - FGF21, fibroblast growth factor 21 KW - GLUT4, glucose transporter 4 KW - HSL, hormone sensitive lipase KW - LM, leg mass KW - Lipolysis KW - Liver KW - PKA, protein kinase A KW - Ra, rate of appearance KW - TG, triacylglycerol KW - VLDL, very low density lipoprotein KW - VO2peak, maximal oxygen consumption SP - 22 EP - 29 JF - Molecular metabolism JO - Mol Metab VL - 6 IS - 1 N2 - 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 Ser660 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. SN - 2212-8778 UR - https://www.unboundmedicine.com/medline/citation/28123934/Circulating_FGF21_in_humans_is_potently_induced_by_short_term_overfeeding_of_carbohydrates_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2212-8778(16)30261-7 DB - PRIME DP - Unbound Medicine ER -