Clinical Research

Adipose tissue contribution to plasma fibroblast growth factor 21 and fibroblast activation protein in obesity

Article metrics

Abstract

Fibroblast growth factor 21 (FGF21) is an important regulator of energy metabolism. FGF21 is inactivated by fibroblast activation protein (FAP). We investigated whether FGF21 and/or FAP are secreted from human white adipose tissue of individuals with obesity by measuring total FGF21, active FGF21, and FAP concentrations in arterialized blood and venous blood draining the subcutaneous abdominal adipose tissue (scAT). Measurements were performed under fasting conditions and after a high fat meal before and after diet-induced weight loss in 16 adults with BMI 27–35 kg/m2. FGF21 was not released from scAT, neither before nor after weight loss in agreement with an undetectable gene expression of FGF21 in this tissue. Although scAT showed significant gene expression of FAP, no release of FAP from the tissue could be detected. The high fat meal increased postprandial circulating FGF21 but not FAP. Circulating levels of FAP but not FGF21 were significantly reduced after weight loss. On the other hand, FAP expression in scAT was increased. In conclusion, release from scAT does not appear to contribute to circulating concentrations of FGF21 and FAP and their responses to ingestion of a high fat meal or weight loss, respectively, in individuals with obesity.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1

References

  1. 1.

    BonDurant LD, Potthoff MJ. Fibroblast growth factor 21: a versatile regulator of metabolic homeostasis. Annu Rev Nutr. 2018;38:173–96.

  2. 2.

    Indrakusuma I, Sell H, Eckel J. Novel mediators of adipose tissue and muscle crosstalk. Curr Obes Rep. 2015;4:411–7.

  3. 3.

    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;57:1246–53.

  4. 4.

    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;71:369–75.

  5. 5.

    Christodoulides C, Dyson P, Sprecher D, Tsintzas K, Karpe F. Circulating fibroblast growth factor 21 is induced by peroxisome proliferator-activated receptor agonists but not ketosis in man. J Clin Endocrinol Metab. 2009;94:3594–601.

  6. 6.

    Mai K, Schwarz F, Bobbert T, Andres J, Assmann A, Pfeiffer AF, et al. Relation between fibroblast growth factor-21, adiposity, metabolism, and weight reduction. Metabolism. 2011;60:306–11.

  7. 7.

    Lips MA, de Groot GH, Berends FJ, Wiezer R, van Wagensveld BA, Swank DJ, et al. Calorie restriction and Roux-en-Y gastric bypass have opposing effects on circulating FGF21 in morbidly obese subjects. Clin Endocrinol. 2014;81:862–70.

  8. 8.

    Haluzikova D, Lacinova Z, Kavalkova P, Drapalova J, Krizova J, Bartlova M, et al. Laparoscopic sleeve gastrectomy differentially affects serum concentrations of FGF-19 and FGF-21 in morbidly obese subjects. Obesity. 2013;21:1335–42.

  9. 9.

    Coppage AL, Heard KR, DiMare MT, Liu Y, Wu W, Lai JH, et al. Human FGF-21 is a substrate of fibroblast activation protein. PLoS ONE. 2016;11:e0151269.

  10. 10.

    Keane FM, Yao TW, Seelk S, Gall MG, Chowdhury S, Poplawski SE, et al. Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs. FEBS Open Bio. 2013;4:43–54.

  11. 11.

    Vink RG, Roumans NJ, Arkenbosch LA, Mariman EC, van Baak MA. The effect of rate of weight loss on long-term weight regain in adults with overweight andobesity. Obesity. 2016;24:321–7.

  12. 12.

    Vink RG, Roumans NJ, van der Kolk BW, Fazelzadeh P, Boekschoten MV, Mariman EC, et al. Adipose tissue meal-derived fatty acid uptake before and after diet-induced weight loss in adults with overweight and obesity. Obesity. 2017;25:1391–9.

  13. 13.

    Roumans NJT, Vink RG, Bouwman FG, Fazelzadeh P, van Baak MA, Mariman ECM. Weight loss-induced cellular stress in subcutaneous adipose tissue and the risk for weight regain in overweight and obese adults. Int J Obes. 2017;41:894–901.

  14. 14.

    Umberger TS, Sloan JH, Chen J, Cheng C, Siegel RW, Qian Y, et al. Novel sandwich immunoassays for the measurement of total and active FGF21. Bioanalysis. 2014;6:3283–93.

  15. 15.

    Dutchak PA, Katafuchi T, Bookout AL, Choi JH, Yu RT, Mangelsdorf DJ, et al. Fibroblast growth factor-21 regulates PPARgamma activity and the antidiabetic actions of thiazolidinediones. Cell. 2012;148:556–67.

  16. 16.

    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;139:456–63.

  17. 17.

    Matikainen N, Taskinen MR, Stennabb S, Lundbom N, Hakkarainen A, Vaaralahti K, et al. Decrease in circulating fibroblast growth factor 21 after an oral fat load is related to postprandial triglyceride-rich lipoproteins and liver fat. Eur J Endocrinol. 2012;166:487–92.

  18. 18.

    Schmid A, Leszczak S, Ober I, Karrasch T, Schaffler A. Short-term and divergent regulation of FGF-19 and FGF-21 during oral lipid tolerance test but not oral glucose tolerance test. Exp Clin Endocrinol Diabetes. 2015;123:88–94.

  19. 19.

    Samms RJ, Lewis JE, Norton L, Stephens FB, Gaffney CJ, Butterfield T, et al. FGF21 is an insulin-dependent postprandial hormone in adult humans. J Clin Endocrinol Metab. 2017;102:3806–13.

  20. 20.

    Yu H, Xia F, Lam KS, Wang Y, Bao Y, Zhang J, et al. Circadian rhythm of circulating fibroblast growth factor 21 is related to diurnal changes in fatty acids in humans. Clin Chem. 2011;57:691–700.

Download references

Author information

MAvB and ECMM conceived the study and RGV and NJTR performed it. ACA and CCC were responsible for the analysis of FGF21 and FAP. MAvB wrote the manuscript. All authors commented on the content and approved the final version.

Correspondence to Marleen A. van Baak.

Ethics declarations

Conflict of interest

MAvB, ECM, RGV, and NJTR declare that they have no conflict of interest. CCC and ACA are employed by Eli Lilly and Company. This study was supported by the Netherlands Organisation for Scientific Research TOP, Grant Number: 200500001.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark