Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Clinical Studies and Practice

Serum fibroblast growth factor 21 in human obesity: regulation by insulin infusion and relationship with glucose and lipid oxidation

International Journal of Obesity volume 37, pages 1386–1390 (2013)Cite this article

Subjects

Abstract

Objective:

Fibroblast growth factor 21 (FGF21) reduces plasma glucose and triglycerides, and increases free fatty acid oxidation in animal models of diabetes. The aim of the present study was to assess the relationships of serum FGF21 with glucose oxidation (GOx) and lipid oxidation (LOx) in the baseline and insulin-stimulated conditions in lean and obese subjects.

Design:

Cross-sectional study.

Subjects:

Eighty-four subjects with normal glucose tolerance, 42 lean (body mass index (BMI) <25 kg m−2) and 42 overweight or obese (BMI between 25 and 40 kg m−2).

Measurements:

Euglycemic hyperinsulinemic clamp and indirect calorimetry in the baseline state and during last 30 min of the clamp. The change in respiratory quotient (ΔRQ) in response to insulin was used as a measure of metabolic flexibility. Serum FGF21 was determined in the baseline state and after the clamp.

Results:

Obese subjects had higher LOx in the baseline and insulin-stimulated conditions, lower insulin-stimulated GOx and ΔRQ (all P<0.05). Fasting serum FGF21 did not differ between the groups. Insulin infusion resulted in an increase in serum FGF21 in the obese (P=0.0001), but not in the lean group (P=0.76). Postclamp serum FGF21 was higher in the obese subjects (P=0.0007). In this group, postclamp FGF21 was related to LOx during the clamp (r=0.32, P=0.044), change in GOx and LOx in response to insulin (r=−0.44, P=0.005; r=0.47, P=0.002; respectively) and ΔRQ (r=−0.50, P=0.001).

Conclusions:

An increase in serum FGF21 in response to insulin in obese subjects might represent inappropriate response, possibly associated with metabolic inflexibility in obesity and insulin resistance.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ et al. FGF-21 as a novel metabolic regulator. J Clin Invest 2005; 115: 1627–1635.

    Article  CAS  Google Scholar 

  2. Badman MK, Pissios P, Kennedy AR, Koukos G, Flier JS, Maratos-Flier E . Hepatic fibroblast growth factor 21 is regulated by PPARα and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab 2007; 5: 426–437.

    Article  CAS  Google Scholar 

  3. Potthoff MJ, Inagaki T, Satapati S, Ding X, He T, Goetz R et al. FGF21 induces PGC1α and regulates carbohydrate metabolism during the adaptive starvation response. PNAS 2009; 106: 10853–10858.

    Article  CAS  Google Scholar 

  4. Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, Parameswara V et al. Endocrine regulation of the fasting response by PPARα-mediated induction of fibroblast growth factor 21. Cell Metab 2007; 5: 415–425.

    Article  CAS  Google Scholar 

  5. Xu J, Lloyd DJ, Hale C, Stanislaus S, Chen M, Sivits G et al. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 2009; 58: 25–259.

    Google Scholar 

  6. Zhang X, Yeung DC, Karpisek M, Stejskal D, Zhou ZG, Liu F et al. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes 2008; 57: 1246–1253.

    Article  CAS  Google Scholar 

  7. Chavez AO, Molina-Carrion M, Abdul-Ghani M, Folli F, DeFronzo RA, Tripathy D . Circulating fibroblast growth factor 21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance. Diabetes Care 2009; 32: 1542–1546.

    Article  CAS  Google Scholar 

  8. Chen WW, Li L, Yang GY, Li K, Qi XY, Zhu W et al. Circulating FGF-21 levels in normal subjects and in newly diagnosed patients with type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2008; 116: 65–68.

    Article  CAS  Google Scholar 

  9. Dushay J, Chui PC, Gopalakrishnan GS, Varela-Rey M, Crawley M, Fisher FM et al. Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease. Gastroenterology 2010; 139: 456–463.

    Article  CAS  Google Scholar 

  10. Li H, Bao Y, Xu A, Pan X, Lu J, Wu H et al. Serum fibroblast growth factor 21 is associated with adverse lipid profiles and γ-glutamyltransferase but not insulin sensitivity in Chinese subjects. J Clin Endocrinol Metab 2009; 94: 2151–2156.

    Article  CAS  Google Scholar 

  11. Fisher FM, Chui PC, Antonellis PJ, Bina HA, Kharitonenkov A, Flier JS et al. Obesity is a fibroblast growth factor 21 (FGF21)-resistant state. Diabetes 2010; 59: 2781–2789.

    Article  CAS  Google Scholar 

  12. Hale C, Chen MM, Stanislaus S, Chinookoswong N, Hager T, Wang M et al. Lack of overt FGF21 resistance in two mouse models of obesity and insulin resistance. Endocrinology 2012; 153: 69–80.

    Article  CAS  Google Scholar 

  13. Mai K, Andres J, Biedasek K, Weicht J, Bobbert T, Sabath M et al. Free fatty acids link metabolism and regulation of insulin-sensitizing fibroblast growth factor 21. Diabetes 2009; 58: 1532–1538.

    Article  CAS  Google Scholar 

  14. Hojman P, Pedersen M, Nielsen AR, Krogh-Madsen R, Yfanti C, Akerstrom T et al. Fibroblastgrowth factor 21 is induced in human skeletal muscles by hyperinsulinemia. Diabetes 2009; 58: 2797–2801.

    Article  CAS  Google Scholar 

  15. Mraz M, Bartlova M, Lacinova Z, Michalsky D, Kasalicky M, Haluzikova D et al. Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity. Clin Endocrinol 2009; 71: 369–375.

    Article  CAS  Google Scholar 

  16. Vienberg SG, Brons C, Nilsson E, Astrup A, Vaag A, Andersen B . Impact of short-term high-fat feeding and insulin-stimulated FGF21 in subjects with low birth weight and controls. Eur J Endocrinol 2012; 167: 49–57.

    Article  CAS  Google Scholar 

  17. Mai K, Bobbert T, Groth C, Assmann A, Meinus S, Kraatz J et al. Physiological modulation of circulating FGF21: relevance of free fatty acids and insulin. Am J Physiol 2010; 299: E126–E130.

    CAS  Google Scholar 

  18. Yang M, Dong J, Liu H, Li L, Yang G . Effects of short-term continuous subcutaneous insulin infusion on fasting plasma fibroblast growth factor-21 levels in patients with newly diagnosed type 2 diabetes mellitus. PLoS ONE 2011; 6: e26359.

    Article  CAS  Google Scholar 

  19. Kelley DE . Skeletal muscle fat oxidation: timing and flexibility are everything. J Clin Invest 2005; 115: 1699–1702.

    Article  CAS  Google Scholar 

  20. Karczewska-Kupczewska M, Kowalska I, Nikołajuk A, Adamska A, Zielińska M, Kamińska N et al. Circulating brain-derived neurotrophic factor concentration is downregulated by intralipid/heparin infusion or high-fat meal in young healthy male subjects. Diabetes Care 2012; 35: 358–362.

    Article  CAS  Google Scholar 

  21. DeFronzo RA, Tobin JD, Andres R . Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214–E223.

    CAS  Google Scholar 

  22. Karczewska-Kupczewska M, Strączkowski M, Adamska A, Nikołajuk A, Otziomek E, Górska M et al. Insulin sensitivity, metabolic flexibility, and serum adiponectin concentration in women with anorexia nervosa. Metabolism 2010; 59: 473–477.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Grant UDA-POIG.01.03.01-00-128/08, from the Program Innovative Economy 2007–2013, part-financed by the European Union within the European Regional Development Fund, and grant 3-50689 from Medical University of Białystok, Poland.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Białystok, Poland,

    M Strączkowski, M Karczewska-Kupczewska, A Adamska, E Otziomek & I Kowalska

  2. Department of Prophylaxis of Metabolic Diseases, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland

    M Strączkowski, M Karczewska-Kupczewska & A Nikołajuk

Authors
  1. M Strączkowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Karczewska-Kupczewska
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Adamska
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Otziomek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I Kowalska
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Nikołajuk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Strączkowski.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Strączkowski, M., Karczewska-Kupczewska, M., Adamska, A. et al. Serum fibroblast growth factor 21 in human obesity: regulation by insulin infusion and relationship with glucose and lipid oxidation. Int J Obes 37, 1386–1390 (2013). https://doi.org/10.1038/ijo.2013.10

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2013.10

Keywords

This article is cited by

Search

Advanced search

Quick links