A B Crujeiras1,2, D Gomez-Arbelaez1, 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, F F Casanueva1,2. 1. Division 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. CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Santiago de Compostela, Spain. 3. Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research, University of Navarra (UNAV) and IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. 4. Medical Department Pronokal, Protein Supplies SL, Barcelona, Spain. 5. Department of Endocrinology and Nutrition, School of Medicine, Center of Investigation of Endocrinology and Nutrition, Hospital Clinico Universitario Valladolid, University of Valladolid, Valladolid, Spain. 6. Division of General Surgery, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain. 7. Unidad 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. Division of Endocrinology, Complejo Hospitalario Universitario de Ferrol and Coruña University, Ferrol, Spain.
Abstract
BACKGROUND: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. OBJECTIVE: 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. RESULTS: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: -62.5 pg ml-1 or -14.8 pg ml-1 and LC diet: -67.9 pg ml-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 (148.8 pg ml-1 higher than baseline). The FGF21 differential changes occur concomitantly with a non-induced ketosis situation (0.66±0.56 mm) in bariatric surgery, and an improvement in adiposity and insulin sensitivity induced by the three therapies. CONCLUSIONS: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.
RCT Entities:
BACKGROUND: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. OBJECTIVE: 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. RESULTS: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: -62.5 pg ml-1 or -14.8 pg ml-1 and LC diet: -67.9 pg ml-1). There were no differences in FGF21 levels between both energy-restriction treatments. On the contrary, after bariatric surgery morbidly obesepatients showed a significant increase in FGF21, especially 1 month after surgery (148.8 pg ml-1 higher than baseline). The FGF21 differential changes occur concomitantly with a non-induced ketosis situation (0.66±0.56 mm) in bariatric surgery, and an improvement in adiposity and insulin sensitivity induced by the three therapies. CONCLUSIONS: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.
Authors: Knut Mai; Franziska Schwarz; Thomas Bobbert; Janin Andres; Anke Assmann; Andreas F H Pfeiffer; Joachim Spranger Journal: Metabolism Date: 2010-04-01 Impact factor: 8.694
Authors: M Mraz; M Bartlova; Z Lacinova; D Michalsky; M Kasalicky; D Haluzikova; M Matoulek; I Dostalova; V Humenanska; M Haluzik Journal: Clin Endocrinol (Oxf) Date: 2008-12-11 Impact factor: 3.478
Authors: Javier Gómez-Ambrosi; José M Gallego-Escuredo; Victoria Catalán; Amaia Rodríguez; Pere Domingo; Rafael Moncada; Víctor Valentí; Javier Salvador; Marta Giralt; Francesc Villarroya; Gema Frühbeck Journal: Clin Nutr Date: 2016-05-04 Impact factor: 7.324
Authors: Pouneh K Fazeli; Mingyue Lun; Soo M Kim; Miriam A Bredella; Spenser Wright; Yang Zhang; Hang Lee; Ciprian Catana; Anne Klibanski; Parth Patwari; Matthew L Steinhauser Journal: J Clin Invest Date: 2015-11-03 Impact factor: 14.808
Authors: Diego Gomez-Arbelaez; Ana B Crujeiras; Ana I Castro; Albert Goday; Antonio Mas-Lorenzo; Ana Bellon; Cristina Tejera; Diego Bellido; Cristobal Galban; Ignacio Sajoux; Patricio Lopez-Jaramillo; Felipe F Casanueva Journal: Endocrine Date: 2017-09-15 Impact factor: 3.633
Authors: Ignacio Sajoux; Paula M Lorenzo; Diego Gomez-Arbelaez; M Angeles Zulet; Itziar Abete; Ana I Castro; Javier Baltar; María P Portillo; Francisco J Tinahones; J Alfredo Martinez; Ana B Crujeiras; Felipe F Casanueva Journal: Nutrients Date: 2019-10-04 Impact factor: 5.717
Authors: Mette S Nielsen; Susanna Søberg; Julie B Schmidt; Anne Chenchar; Anders Sjödin; Matthew P Gillum Journal: PeerJ Date: 2021-04-14 Impact factor: 2.984
Authors: Ana I Castro; Diego Gomez-Arbelaez; Ana B Crujeiras; Roser Granero; Zaida Aguera; Susana Jimenez-Murcia; Ignacio Sajoux; Patricio Lopez-Jaramillo; Fernando Fernandez-Aranda; Felipe F Casanueva Journal: Nutrients Date: 2018-09-21 Impact factor: 5.717
Authors: Úrsula Martínez-Garza; Daniel Torres-Oteros; Alex Yarritu-Gallego; Pedro F Marrero; Diego Haro; Joana Relat Journal: Int J Mol Sci Date: 2019-09-21 Impact factor: 5.923