Original Article

International Journal of Obesity (2017) 41, 1570–1578; doi:10.1038/ijo.2017.138; published online 4 July 2017

Clinical Studies and Practice

Plasma FGF21 levels in obese patients undergoing energy-restricted diets or bariatric surgery: a marker of metabolic stress?

A B Crujeiras1,2,9, D Gomez-Arbelaez1,9, M A Zulet2,3, M C Carreira1,2, I Sajoux4, D de Luis5, A I Castro1,2, J Baltar6, I Baamonde6, A Sueiro1, M Macias-Gonzalez2,7, D Bellido8, F J Tinahones2,7, J A Martinez2,3 and F F Casanueva1,2

  1. 1Division of Endocrinology, Department of Medicine, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigación Sanitaria de Santiago (IDIS) and Santiago de Compostela University (USC), Santiago de Compostela, La Coruña, Spain
  2. 2CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Santiago de Compostela, Spain
  3. 3Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research, University of Navarra (UNAV) and IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
  4. 4Medical Department Pronokal, Protein Supplies SL, Barcelona, Spain
  5. 5Department of Endocrinology and Nutrition, School of Medicine, Center of Investigation of Endocrinology and Nutrition, Hospital Clinico Universitario Valladolid, University of Valladolid, Valladolid, Spain
  6. 6Division of General Surgery, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain
  7. 7Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Complejo Hospitalario de Málaga (Virgen de la Victoria), University of Málaga, Málaga, Spain
  8. 8Division of Endocrinology, Complejo Hospitalario Universitario de Ferrol and Coruña University, Ferrol, Spain

Correspondence: Dr FF Casanueva, Division of Endocrinology, Department of Medicine, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigación Sanitaria de Santiago (IDIS), Travesía da Choupana Street s/n, 15706 Santiago de Compostela, La Coruña, Spain. E-mail: endocrine@usc.es or anabelencrujeiras@hotmail.com

9These authors contributed equally to this work.

Received 7 March 2017; Revised 10 May 2017; Accepted 25 May 2017
Accepted article preview online 7 June 2017; Advance online publication 4 July 2017





Fibroblast growth factor 21 (FGF21) has been suggested to be an endocrine signal of nutritional status and an active regulator of metabolism. However, there is no agreement on the effect of weight-loss therapies on circulating levels of FGF21 in humans.



To assess FGF21 circulating levels in adiposity excess and after different weight-loss strategies prescribed in five different groups from four independent centers.

Subjects and methods:


Body composition, ketosis, insulin sensitivity and FGF21 were evaluated in 181 excess body weight and 14 normal-weight subjects. From the excess body weight patients, two independent groups (discovery cohort; n=20 and validation cohort; n=28) undertook a very low-calorie ketogenic (VLCK) diet, a third group followed a low-calorie (LC) diet (n=84) and other two groups underwent bariatric surgery (discovery cohort; n=24 and validation cohort; n=25). The follow-up was 4 to 6 or 12 months, respectively.



FGF21 levels were higher in excess body weight patients than in normal-weight subjects. The energy-restriction therapy to lose weight induced a significant decrease, with respect to baseline, in circulating levels of FGF21 (VLCK: −62.5pgml−1 or −14.8pgml−1 and LC diet: −67.9 pgml−1). There were no differences in FGF21 levels between both energy-restriction treatments. On the contrary, after bariatric surgery morbidly obese patients showed a significant increase in FGF21, especially 1 month after surgery (148.8pgml−1 higher than baseline). The FGF21 differential changes occur concomitantly with a non-induced ketosis situation (0.66±0.56mm) in bariatric surgery, and an improvement in adiposity and insulin sensitivity induced by the three therapies.



FGF21 levels were reduced after energy-restricted treatments and severely increased after bariatric surgery, independently of the weight reduction magnitude, insulin sensitivity or ketosis. Therefore, FGF21 appears to be a marker of severe nutritional stress.

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