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The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans.

Publication ,  Journal Article
Ter Horst, KW; Gilijamse, PW; Demirkiran, A; van Wagensveld, BA; Ackermans, MT; Verheij, J; Romijn, JA; Nieuwdorp, M; Maratos-Flier, E ...
Published in: Mol Metab
November 2017

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.

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Published In

Mol Metab

DOI

EISSN

2212-8778

Publication Date

November 2017

Volume

6

Issue

11

Start / End Page

1493 / 1502

Location

Germany

Related Subject Headings

  • Weight Loss
  • Obesity, Morbid
  • Obesity
  • Middle Aged
  • Male
  • Liver
  • Insulin Resistance
  • Insulin
  • Humans
  • Glucose
 

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Ter Horst, K. W., Gilijamse, P. W., Demirkiran, A., van Wagensveld, B. A., Ackermans, M. T., Verheij, J., … Serlie, M. J. (2017). The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans. Mol Metab, 6(11), 1493–1502. https://doi.org/10.1016/j.molmet.2017.08.014
Ter Horst, Kasper W., Pim W. Gilijamse, Ahmet Demirkiran, Bart A. van Wagensveld, Mariette T. Ackermans, Joanne Verheij, Johannes A. Romijn, et al. “The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans.Mol Metab 6, no. 11 (November 2017): 1493–1502. https://doi.org/10.1016/j.molmet.2017.08.014.
Ter Horst KW, Gilijamse PW, Demirkiran A, van Wagensveld BA, Ackermans MT, Verheij J, et al. The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans. Mol Metab. 2017 Nov;6(11):1493–502.
Ter Horst, Kasper W., et al. “The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans.Mol Metab, vol. 6, no. 11, Nov. 2017, pp. 1493–502. Pubmed, doi:10.1016/j.molmet.2017.08.014.
Ter Horst KW, Gilijamse PW, Demirkiran A, van Wagensveld BA, Ackermans MT, Verheij J, Romijn JA, Nieuwdorp M, Maratos-Flier E, Herman MA, Serlie MJ. The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans. Mol Metab. 2017 Nov;6(11):1493–1502.
Journal cover image

Published In

Mol Metab

DOI

EISSN

2212-8778

Publication Date

November 2017

Volume

6

Issue

11

Start / End Page

1493 / 1502

Location

Germany

Related Subject Headings

  • Weight Loss
  • Obesity, Morbid
  • Obesity
  • Middle Aged
  • Male
  • Liver
  • Insulin Resistance
  • Insulin
  • Humans
  • Glucose