The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans
Objective: Fructose consumption has been implicated in the development of obesity and insulin resistance. Emerging evidence shows that fibroblast growth factor 21 (FGF21) has beneficial effects on glucose, lipid, and energy metabolism and may also mediate an adaptive response to fructose ingestion....
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doaj-45fb8f00eaf645dcbdade66a9f0d30fd2020-11-25T00:01:27ZengElsevierMolecular Metabolism2212-87782017-11-016111493150210.1016/j.molmet.2017.08.014The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humansKasper W. ter Horst0Pim W. Gilijamse1Ahmet Demirkiran2Bart A. van Wagensveld3Mariette T. Ackermans4Joanne Verheij5Johannes A. Romijn6Max Nieuwdorp7Eleftheria Maratos-Flier8Mark A. Herman9Mireille J. Serlie10Department of Endocrinology and Metabolism, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The NetherlandsDepartment of Endocrinology and Metabolism, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The NetherlandsDepartment of Surgery, Red Cross Hospital, Vondellaan 13, 1942LE Beverwijk, The NetherlandsDepartment of Surgery, OLVG, Postbus 9243, 1006AE Amsterdam, The NetherlandsDepartment of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The NetherlandsDepartment of Pathology, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The NetherlandsDepartment of Medicine, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The NetherlandsDepartment of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The NetherlandsDivision of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Center for Life Sciences, Boston, MA 02215, USADivision of Endocrinology, Metabolism and Nutrition, Duke University School of Medicine, 300 N. Duke Street, Carmichael Building, Durham, NC 27701, USADepartment of Endocrinology and Metabolism, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The NetherlandsObjective: Fructose consumption has been implicated in the development of obesity and insulin resistance. Emerging evidence shows that fibroblast growth factor 21 (FGF21) has beneficial effects on glucose, lipid, and energy metabolism and may also mediate an adaptive response to fructose ingestion. Fructose acutely stimulates circulating FGF21 consistent with a hormonal response. We aimed to evaluate whether fructose-induced FGF21 secretion is linked to metabolic outcomes in obese humans before and after bariatric surgery-induced weight loss. Methods: We recruited 40 Roux-en-Y gastric bypass patients and assessed the serum FGF21 response to fructose (75-g fructose tolerance test) and basal and insulin-mediated glucose and lipid fluxes during a 2-step hyperinsulinemic-euglycemic clamp with infusion of [6,6-2H2] glucose and [1,1,2,3,3-2H5] glycerol. Liver biopsies were obtained during bariatric surgery. Nineteen subjects underwent the same assessments at 1-year follow-up. Results: Serum FGF21 increased 3-fold at 120 min after fructose ingestion and returned to basal levels at 300 min. Neither basal FGF21 nor the fructose-FGF21 response correlated with liver fat content or liver histopathology, but increased levels were associated with elevated endogenous glucose production, increased lipolysis, and peripheral/muscle insulin resistance. At 1-year follow-up, subjects had lost 28 ± 6% of body weight and improved in all metabolic outcomes, but fructose-stimulated FGF21 dynamics did not markedly differ from the pre-surgical state. The association between increased basal and stimulated FGF21 levels with poor metabolic health was no longer present after weight loss. Conclusions: Fructose ingestion in obese humans stimulates FGF21 secretion, and this response is related to systemic metabolism. Further studies are needed to establish if FGF21 signaling is (patho)physiologically involved in fructose metabolism and metabolic health.http://www.sciencedirect.com/science/article/pii/S2212877817306105FructoseFGF21Insulin resistanceHyperinsulinemic-euglycemic clampObesityTranslational study |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kasper W. ter Horst Pim W. Gilijamse Ahmet Demirkiran Bart A. van Wagensveld Mariette T. Ackermans Joanne Verheij Johannes A. Romijn Max Nieuwdorp Eleftheria Maratos-Flier Mark A. Herman Mireille J. Serlie |
spellingShingle |
Kasper W. ter Horst Pim W. Gilijamse Ahmet Demirkiran Bart A. van Wagensveld Mariette T. Ackermans Joanne Verheij Johannes A. Romijn Max Nieuwdorp Eleftheria Maratos-Flier Mark A. Herman Mireille J. Serlie The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans Molecular Metabolism Fructose FGF21 Insulin resistance Hyperinsulinemic-euglycemic clamp Obesity Translational study |
author_facet |
Kasper W. ter Horst Pim W. Gilijamse Ahmet Demirkiran Bart A. van Wagensveld Mariette T. Ackermans Joanne Verheij Johannes A. Romijn Max Nieuwdorp Eleftheria Maratos-Flier Mark A. Herman Mireille J. Serlie |
author_sort |
Kasper W. ter Horst |
title |
The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans |
title_short |
The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans |
title_full |
The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans |
title_fullStr |
The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans |
title_full_unstemmed |
The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans |
title_sort |
fgf21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans |
publisher |
Elsevier |
series |
Molecular Metabolism |
issn |
2212-8778 |
publishDate |
2017-11-01 |
description |
Objective: Fructose consumption has been implicated in the development of obesity and insulin resistance. Emerging evidence shows that fibroblast growth factor 21 (FGF21) has beneficial effects on glucose, lipid, and energy metabolism and may also mediate an adaptive response to fructose ingestion. Fructose acutely stimulates circulating FGF21 consistent with a hormonal response. We aimed to evaluate whether fructose-induced FGF21 secretion is linked to metabolic outcomes in obese humans before and after bariatric surgery-induced weight loss.
Methods: We recruited 40 Roux-en-Y gastric bypass patients and assessed the serum FGF21 response to fructose (75-g fructose tolerance test) and basal and insulin-mediated glucose and lipid fluxes during a 2-step hyperinsulinemic-euglycemic clamp with infusion of [6,6-2H2] glucose and [1,1,2,3,3-2H5] glycerol. Liver biopsies were obtained during bariatric surgery. Nineteen subjects underwent the same assessments at 1-year follow-up.
Results: Serum FGF21 increased 3-fold at 120 min after fructose ingestion and returned to basal levels at 300 min. Neither basal FGF21 nor the fructose-FGF21 response correlated with liver fat content or liver histopathology, but increased levels were associated with elevated endogenous glucose production, increased lipolysis, and peripheral/muscle insulin resistance. At 1-year follow-up, subjects had lost 28 ± 6% of body weight and improved in all metabolic outcomes, but fructose-stimulated FGF21 dynamics did not markedly differ from the pre-surgical state. The association between increased basal and stimulated FGF21 levels with poor metabolic health was no longer present after weight loss.
Conclusions: Fructose ingestion in obese humans stimulates FGF21 secretion, and this response is related to systemic metabolism. Further studies are needed to establish if FGF21 signaling is (patho)physiologically involved in fructose metabolism and metabolic health. |
topic |
Fructose FGF21 Insulin resistance Hyperinsulinemic-euglycemic clamp Obesity Translational study |
url |
http://www.sciencedirect.com/science/article/pii/S2212877817306105 |
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